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Moxetumomab Pasudotox for Advanced Hairy Cell Leukemia

Primary Purpose

Leukemia, Hairy Cell

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Moxetumomab pasudotox
IV Bag Protectant for Moxetumomab pasudotox
Sponsored by
MedImmune LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Hairy Cell focused on measuring Moxetumomab Pasudotox, CAT-8015, Anti-cd22 recombinant immunotoxin, Biologic Therapy, Monoclonal Antibody, Pseudomonas Exotoxin, Targeted Therapy

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers
  • INCLUSION CRITERIA:
  • Patients must have histologically confirmed hairy cell leukemia or hairy cell leukemia variant .with a need for therapy
  • Patients must be Pseudomonas-immunotoxin naive
  • Patients must have had at least 2 prior purine analogs, or at least 1 course of purine analog and 1 of either rituximab or BRAF inhibitor.
  • Men or women age greater than or equal to 18 years.
  • ECOG performance status less than or equal to 2.
  • Patients must have adequate organ function

EXCLUSION CRITERIA

  • Patients who have had chemotherapy, immunotherapy or radiotherapy within 4 weeks prior to entering the study.
  • Patients who are receiving any other investigational agents.
  • Patients with known brain metastases should be excluded from this clinical trial
  • Patients with clinically significant ophthalmologic findings during screening
  • Pregnant or breastfeeding females.
  • Positive for Hepatitis B core antibody or surface antigen unless the patient is on Lamivudine or Entecavir and Hepatitis B Viral DNA load is less than 2000 IU/mL.
  • Active second malignancy requiring treatment other than minor resection of indolent cancers like basal cell and squamous skin cancers
  • HIV-positive patients unless taking appropriate anti-HIV medications with a CD4 count of greater than 200.
  • History of allogeneic bone marrow transplant.
  • Patients with history of both thromboembolism and known congenital hypercoagulable conditions.
  • Uncontrolled pulmonary infection, pulmonary edema.
  • Adequate oxygen saturation
  • Radioimmunotherapy within 2 years prior to enrollment in study.
  • Adequate hematologic function
  • Adequate lung function
  • Patients with history of thrombotic microangiopathy or thrombotic microangiopathy / hemolytic uremic syndrome
  • Patients with QTc interval (Friderica) elevation > 500 msec based on at least 2 separate 12-lead ECGs
  • Patient on high dose estrogen
  • Patients with clinical evidence of disseminated intravascular coagulation

Sites / Locations

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Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Moxetumomab pasudotox 40 µg/kg

Arm Description

Patients will receive Moxetumomab Pasudotox intravenously (IV) over 30 minutes on days 1, 3, 5 of each 28 day cycle for a maximum of 6 cycles or until disease progression, unacceptable toxivity, initiation of alternate therapy or documented CR.

Outcomes

Primary Outcome Measures

Percentage of Participants With Durable Complete Response (CR) Assessed by Blinded Independent Central Review
Durable CR was defined as overall response that meets blood, bone marrow and imaging criteria for CR, followed by a >180 day duration of hematologic remission (HR). CR requires all of the following to be present: No evidence of leukemic cells in peripheral blood and/or by routine H/E staining of bone marrow; Resolution of any hepatomegaly, splenomegaly, and abnormal (>= 2 cm minimum length) lymphadenopathy by CT or MRI (maximum diameter of spleen should be either < 17 cm or have decreased by >25% from its baseline.); HR requires normal complete blood count (CBC) as exhibited by: Neutrophils >= 1.5 x 10^9/L, Platelets >= 100 x 10^9/L, and hemoglobin >= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.
Percentage of Participants With Durable CR by Investigator's Assessment
Durable CR was defined as overall response that meets blood, bone marrow and imaging criteria for CR, followed by a >180 day duration of HR. CR requires all of the following to be present: No evidence of leukemic cells in peripheral blood and/or by routine H/E staining of bone marrow; Resolution of any hepatomegaly, splenomegaly, and abnormal (>= 2 cm minimum length) lymphadenopathy by CT or MRI (maximum diameter of spleen should be either < 17 cm or have decreased by >25% from its baseline.); HR requires normal complete blood count (CBC) as exhibited by: Neutrophils >= 1.5 x 10^9/L, Platelets >= 100 x 10^9/L, and hemoglobin >= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.

Secondary Outcome Measures

Percentage of Participants With Minimal Residual Disease (MRD) Positive or MRD Negative CR Assessed by Blinded Independent Central Review
The MRD status by blinded independent review refers specifically to results of central pathologist read of bone marrow biopsy by immunohistochemistry. The CR with Positive or Negative MRD requires all of the following to be present: No evidence of leukemic cells in the peripheral blood and/or by routine H/E staining of bone marrow. Minimal Residual Disease: CR with HCL evident in blood or in bone marrow biopsy by immunohistochemistry. Resolution of any hepatomegaly, splenomegaly, and abnormal (>= 2 cm minimum length) lymphadenopathy by CT or MRI. Although a normal spleen size is not defined, the maximum diameter of the spleen should be either < 17 cm or have decreased by >25% from its baseline. Normal CBC as exhibited by: Neutrophils >= 1.5 x 10^9/L, Platelets >= 100 x 10^9/L, and hemoglobin >= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.
Percentage of Participants With MRD Positive or MRD Negative CR by Investigator's Assessment
The MRD status by investigator refers to results of investigator assessment of bone marrow biopsy or bone marrow aspirate by immunohistochemistry and/or flow cytometry. The CR with Positive or Negative MRD requires all of the following to be present: No evidence of leukemic cells in the peripheral blood and/or by routine H/E staining of bone marrow. Minimal Residual Disease: CR with HCL evident in blood or marrow by flow cytometry. Resolution of any hepatomegaly, splenomegaly, and abnormal (>= 2 cm minimum length) lymphadenopathy by CT or MRI. Although a normal spleen size is not defined, the maximum diameter of the spleen should be either < 17 cm or have decreased by >25% from its baseline. Normal CBC as exhibited by: Neutrophils >= 1.5 x 10^9/L, Platelets >= 100 x 10^9/L, and hemoglobin >= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.
Time to CR Assessed by Blinded Independent Central Review
Time to CR was defined as the time from the start of moxetumomab pasudotox administration to the first documentation of CR.
Duration of CR Assessed by Blinded Independent Central Review
Duration of CR was defined as the duration from documentation of CR to the time of relapse from CR. Relapse from CR was defined as any CR criteria (blood counts, imaging or bone marrow) no longer consistent with CR. CR requires all of the following to be present: No evidence of leukemic cells in peripheral blood and/or by routine H/E staining of bone marrow; Resolution of any hepatomegaly, splenomegaly, and abnormal (>= 2 cm minimum length) lymphadenopathy by CT or MRI (maximum diameter of spleen should be either < 17 cm or have decreased by >25% from its baseline); normal CBC as exhibited by: Neutrophils >= 1.5 x 10^9/L, Platelets >= 100 x 10^9/L, and hemoglobin >= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.
Duration of Hematologic Remission
Duration of HR was defined as the duration from documentation of HR to the time of relapse. HR was defined as the blood counts required for CR as normal CBC as exhibited by: Neutrophils >= 1.5 x 10^9/L, Platelets >= 100 x 10^9/L, and hemoglobin >= 11.0 g/dL without transfusions or growth factors for at least 4 weeks. Duration of HR was censored on the date of the last hematologic assessment for participants who have no documented relapse based on blood count prior to data cutoff, dropout, or initiation of alternative anticancer therapy.
Time to Hematologic Remission
Time to HR was defined as the time from the start of moxetumomab pasudotox administration to the first documentation of HR. HR was defined as the blood counts required for CR as normal CBC as exhibited by: Neutrophils >= 1.5 x 10^9/L, Platelets >= 100 x 10^9/L, and hemoglobin >= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.
Percentage of Participants With Objective Response (OR) Assessed by Blinded Independent Central Review
The OR was defined as number of participants with a best response of CR or PR. CR requires all of following to be present: No evidence of leukemic cells in peripheral blood and/or by routine H/E staining of bone marrow; Resolution of any hepatomegaly, splenomegaly, and abnormal (>=2 cm minimum length) lymphadenopathy by CT or MRI (maximum diameter of spleen should be either <17 cm or have decreased by >25% from its baseline); normal CBC (Neutrophils >=1.5 x 10^9/L, Platelets >=100 x 10^9/L, and hemoglobin >=11.0 g/dL) without transfusions or growth factors for at least 4 weeks. PR requires all of following for a period of at least 4 weeks: >=50% decrease or normalization (<5.0 x 10^9/L) in peripheral blood lymphocyte count and >=50% reduction in lymphadenopathy and in abnormal haepatosplenomegaly by CT or MRI from pre-treatment baseline value; normal CBC as mentioned above or 50% improvement in CBC values over baseline without transfusions or growth factors for at least 4 weeks.
Percentage of Participants With Objective Response by Investigator's Assessment
The OR was defined as number of participants with a best response of CR or PR. CR requires all of following to be present: No evidence of leukemic cells in peripheral blood and/or by routine H/E staining of bone marrow; Resolution of any hepatomegaly, splenomegaly, and abnormal (>=2 cm minimum length) lymphadenopathy by CT or MRI (maximum diameter of spleen should be either <17 cm or have decreased by >25% from its baseline); normal CBC (Neutrophils >=1.5 x 10^9/L, Platelets >=100 x 10^9/L, and hemoglobin >=11.0 g/dL) without transfusions or growth factors for at least 4 weeks. PR requires all of following for a period of at least 4 weeks: >=50% decrease or normalization (<5.0 x 10^9/L) in peripheral blood lymphocyte count and >=50% reduction in lymphadenopathy and in abnormal haepatosplenomegaly by CT or MRI from pre-treatment baseline value; normal CBC as mentioned above or 50% improvement in CBC values over baseline without transfusions or growth factors for at least 4 weeks.
Time to Objective Response Assessed by Blinded Independent Central Review
Time to OR was defined as the time from the start of moxetumomab pasudotox administration to the first documentation of OR (CR or PR).
Duration of Objective Response Assessed by Blinded Independent Central Review
Duration of OR was defined as the time from the first documentation of objective response (CR or PR) to the date of relapse. Duration of OR was censored on the date of last disease assessment or hematologic assessment for participants who have no documented relapse prior to data cut-off, dropout, or the initiation of alternative anticancer therapy.
Progression-free Survival (PFS) Assessed by Blinded Independent Central Review
The PFS was defined as the time from the start of moxetumomab pasudotox administration to the earliest date of a disease assessment showing a progressive disease/relapse, earliest date of hematologic relapse or date of death, whichever was earlier. The PFS was censored on the date of last disease assessment or hematologic assessment for participants who are alive with no documented relapse or PD prior to data cut-off, dropout, or the initiation of alternative anticancer therapy.
Time to Treatment Failure (TTF) Assessed by Blinded Independent Central Review
The TTF was defined as the time from the start of moxetumomab pasudotox administration to the date of the first of relapse, progressive disease, initiation of alternative anticancer therapy, or death due to disease or disease-related complication. The TTF was censored on the date of last disease assessment or hematologic assessment for participants who are alive with no documented relapse or PD prior to data cut-off, dropout, or the initiation of alternative anticancer therapy and also censored for death not accompanied by relapse.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An Adverse Event (AE) is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. A serious adverse event (SAE) is an AE that results in death, initial or prolonged inpatient hospitalization, life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, or an important medical event. TEAEs and TESAEs are defined as AEs and SAEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug.
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs
An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 30 days after the last dose of study drug (approximately 7 months).
Number of Participants With Abnormal Vital Signs Reported as TEAEs
An abnormal vital signs that were judged by the investigator to be medically significant were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 30 days after the last dose of study drug (approximately 7 months).
Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs
An abnormal ECG findings that were judged by the investigator to be medically significant were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 30 days after the last dose of study drug (approximately 7 months).
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox
The Tmax of moxetumomab pasudotox is reported.
Maximum Observed Plasma Concentration (Cmax) of Moxetumomab Pasudotox
The Cmax of moxetumomab pasudotox is reported.
Time of Last (Tlast) Measurable Concentration of Moxetumomab Pasudotox
The Tlast of moxetumomab pasudotox is reported.
Area Under the Plasma Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC0-last) of Moxetumomab Pasudotox
The AUC0-last of moxetumomab pasudotox is reported.
Area Under the Plasma Concentration-time Curve From Time Zero to 3 Hours (AUC0-3hr) Post End of Moxetumomab Pasudotox
The AUC0-3hr of moxetumomab pasudotox is reported.
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Moxetumomab Pasudotox
The AUC0-inf of moxetumomab pasudotox is reported.
Area Under the Plasma Concentration-time Curve Extrapolated (AUCExt) of Moxetumomab Pasudotox
The AUCExt of moxetumomab pasudotox is reported.
Systemic Clearance (CL) of Moxetumomab Pasudotox
The CL of moxetumomab pasudotox is reported.
Terminal Half Life (t1/2) of Moxetumomab Pasudotox
The t1/2 of moxetumomab pasudotox is reported.
Percentage of Participants With Positive Anti-drug Antibodies (ADA), Neutralizing Anti-drug Antibodies (nAb) and Specificity (CD22 and PE38) Positive to Moxetumomab Pasudotox
Participants with ADA positive, nAb positive, cluster of differentiation 22 (CD22) positive of ADA positive/NAb positive, and pseudomonas exotoxin 38 (PE38) positive of ADA positive/NAb positive to moxetumomab pasudotox at any visit are reported.

Full Information

First Posted
April 9, 2013
Last Updated
March 27, 2020
Sponsor
MedImmune LLC
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1. Study Identification

Unique Protocol Identification Number
NCT01829711
Brief Title
Moxetumomab Pasudotox for Advanced Hairy Cell Leukemia
Official Title
A Pivotal Multicenter Trial of Moxetumomab Pasudotox in Relapsed/ Refractory Hairy Cell Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
April 29, 2013 (Actual)
Primary Completion Date
May 24, 2017 (Actual)
Study Completion Date
April 29, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MedImmune LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Background: - Moxetumomab pasudotox is an experimental non-chemotherapy cancer treatment drug. It targets CD22, a molecule on the surface of essentially all hairy cell leukemia cells. Moxetumomab pasudotox binds to CD22, goes into the cell, and releases a toxin which kills the cell. In a phase I trial it had activity in relapsed/refractory hairy cell leukemia with safety profile supporting further clinical study (http://ncbi.nlm.nih.gov/pubmed/22355053). This is a phase III multicenter trial designed to confirm these results.
Detailed Description
Background: Hairy cell leukemia (HCL) is an indolent B-cell leukemia comprising 2% of all leukemias, or approximately 900 of the 44,000 new cases of leukemia/year in the US Over the last two decades, immunotoxin research has accumulated to support a role for CD22-targeted therapy in the treatment of HCL. Moxetumomab pasudotox is a recombinant immunotoxin containing an Fv fragment of an anti-CD22 monoclonal antibody and truncated Pseudomonas exotoxin. Moxetumomab pasudotox has demonstrated a high complete response (CR) rate in patients with chemoresistant HCL and has shown activity in pediatric acute lymphoblastic leukemia as well. Modification of the structure of moxetumomab pasudotox has greatly improved binding and cytotoxicity toward CD22 expressing malignant cells compared to the precursor molecule. Preclinical and clinical studies have demonstrated that this increase in binding affinity results in improved antitumor activity and tolerability Currently there are no approved agents with significant efficacy for HCL patients after failure of standard therapy Design: This is a multicenter, single-arm study of moxetumomab pasudotox in patients with relapsed/refractory hairy cell leukemia. 77 patients will be enrolled to receive moxetumomab pasudotox intravenously (IV) on days 1, 3 and 5 of each 28 day cycle for a maximum of 6 cycles or until disease progression, unacceptable toxicity occurs, the subject begins alternate therapy, or documented CR (for subjects who have no assessable minimal residual disease and not to exceed 6 cycles). If less than or equal to 2 of the first 25 patients do not achieve durable CR, no additional patients will be accrued. The overall IRB accrual ceiling is currently set at 80 to allow for a small number of patients that cannot be assessed for response.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Hairy Cell
Keywords
Moxetumomab Pasudotox, CAT-8015, Anti-cd22 recombinant immunotoxin, Biologic Therapy, Monoclonal Antibody, Pseudomonas Exotoxin, Targeted Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
80 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Moxetumomab pasudotox 40 µg/kg
Arm Type
Experimental
Arm Description
Patients will receive Moxetumomab Pasudotox intravenously (IV) over 30 minutes on days 1, 3, 5 of each 28 day cycle for a maximum of 6 cycles or until disease progression, unacceptable toxivity, initiation of alternate therapy or documented CR.
Intervention Type
Drug
Intervention Name(s)
Moxetumomab pasudotox
Intervention Type
Drug
Intervention Name(s)
IV Bag Protectant for Moxetumomab pasudotox
Primary Outcome Measure Information:
Title
Percentage of Participants With Durable Complete Response (CR) Assessed by Blinded Independent Central Review
Description
Durable CR was defined as overall response that meets blood, bone marrow and imaging criteria for CR, followed by a >180 day duration of hematologic remission (HR). CR requires all of the following to be present: No evidence of leukemic cells in peripheral blood and/or by routine H/E staining of bone marrow; Resolution of any hepatomegaly, splenomegaly, and abnormal (>= 2 cm minimum length) lymphadenopathy by CT or MRI (maximum diameter of spleen should be either < 17 cm or have decreased by >25% from its baseline.); HR requires normal complete blood count (CBC) as exhibited by: Neutrophils >= 1.5 x 10^9/L, Platelets >= 100 x 10^9/L, and hemoglobin >= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.
Time Frame
Full disease assessment (CBC, bone marrow and imaging) at end of treatment (EOT; up to 24 weeks) and post EOT Day 181; CBC monthly for 6 months post EOT, every 3 months post Day 181 for first 2 years and every 6 months thereafter (approximately 6 years)
Title
Percentage of Participants With Durable CR by Investigator's Assessment
Description
Durable CR was defined as overall response that meets blood, bone marrow and imaging criteria for CR, followed by a >180 day duration of HR. CR requires all of the following to be present: No evidence of leukemic cells in peripheral blood and/or by routine H/E staining of bone marrow; Resolution of any hepatomegaly, splenomegaly, and abnormal (>= 2 cm minimum length) lymphadenopathy by CT or MRI (maximum diameter of spleen should be either < 17 cm or have decreased by >25% from its baseline.); HR requires normal complete blood count (CBC) as exhibited by: Neutrophils >= 1.5 x 10^9/L, Platelets >= 100 x 10^9/L, and hemoglobin >= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.
Time Frame
Full disease assessment (CBC, bone marrow and imaging) at end of treatment (EOT; up to 24 weeks) and post EOT Day 181; CBC monthly for 6 months post EOT, every 3 months post Day 181 for first 2 years and every 6 months thereafter (approximately 6 years)
Secondary Outcome Measure Information:
Title
Percentage of Participants With Minimal Residual Disease (MRD) Positive or MRD Negative CR Assessed by Blinded Independent Central Review
Description
The MRD status by blinded independent review refers specifically to results of central pathologist read of bone marrow biopsy by immunohistochemistry. The CR with Positive or Negative MRD requires all of the following to be present: No evidence of leukemic cells in the peripheral blood and/or by routine H/E staining of bone marrow. Minimal Residual Disease: CR with HCL evident in blood or in bone marrow biopsy by immunohistochemistry. Resolution of any hepatomegaly, splenomegaly, and abnormal (>= 2 cm minimum length) lymphadenopathy by CT or MRI. Although a normal spleen size is not defined, the maximum diameter of the spleen should be either < 17 cm or have decreased by >25% from its baseline. Normal CBC as exhibited by: Neutrophils >= 1.5 x 10^9/L, Platelets >= 100 x 10^9/L, and hemoglobin >= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.
Time Frame
Prior to each treatment cycle, EOT (up to 24 weeks), monthly from the EOT assessment until the Day 181 assessment (only for CBC), at follow-up visits every 3 months for the next 24 months, and every 6 months thereafter (approximately 6 years)
Title
Percentage of Participants With MRD Positive or MRD Negative CR by Investigator's Assessment
Description
The MRD status by investigator refers to results of investigator assessment of bone marrow biopsy or bone marrow aspirate by immunohistochemistry and/or flow cytometry. The CR with Positive or Negative MRD requires all of the following to be present: No evidence of leukemic cells in the peripheral blood and/or by routine H/E staining of bone marrow. Minimal Residual Disease: CR with HCL evident in blood or marrow by flow cytometry. Resolution of any hepatomegaly, splenomegaly, and abnormal (>= 2 cm minimum length) lymphadenopathy by CT or MRI. Although a normal spleen size is not defined, the maximum diameter of the spleen should be either < 17 cm or have decreased by >25% from its baseline. Normal CBC as exhibited by: Neutrophils >= 1.5 x 10^9/L, Platelets >= 100 x 10^9/L, and hemoglobin >= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.
Time Frame
Prior to each treatment cycle, end of treatment, and at follow-up visits every 3 months for the next 24 months and every 6 months thereafter (Approximately 6 years)
Title
Time to CR Assessed by Blinded Independent Central Review
Description
Time to CR was defined as the time from the start of moxetumomab pasudotox administration to the first documentation of CR.
Time Frame
Prior to each treatment cycle, EOT (up to 24 weeks), monthly from the EOT assessment until the Day 181 assessment (only for CBC), at follow-up visits every 3 months for the next 24 months, and every 6 months thereafter (approximately 6 years)
Title
Duration of CR Assessed by Blinded Independent Central Review
Description
Duration of CR was defined as the duration from documentation of CR to the time of relapse from CR. Relapse from CR was defined as any CR criteria (blood counts, imaging or bone marrow) no longer consistent with CR. CR requires all of the following to be present: No evidence of leukemic cells in peripheral blood and/or by routine H/E staining of bone marrow; Resolution of any hepatomegaly, splenomegaly, and abnormal (>= 2 cm minimum length) lymphadenopathy by CT or MRI (maximum diameter of spleen should be either < 17 cm or have decreased by >25% from its baseline); normal CBC as exhibited by: Neutrophils >= 1.5 x 10^9/L, Platelets >= 100 x 10^9/L, and hemoglobin >= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.
Time Frame
Prior to each treatment cycle, EOT (up to 24 weeks), monthly from the EOT assessment until the Day 181 assessment (only for CBC), at follow-up visits every 3 months for the next 24 months, and every 6 months thereafter (approximately 6 years)
Title
Duration of Hematologic Remission
Description
Duration of HR was defined as the duration from documentation of HR to the time of relapse. HR was defined as the blood counts required for CR as normal CBC as exhibited by: Neutrophils >= 1.5 x 10^9/L, Platelets >= 100 x 10^9/L, and hemoglobin >= 11.0 g/dL without transfusions or growth factors for at least 4 weeks. Duration of HR was censored on the date of the last hematologic assessment for participants who have no documented relapse based on blood count prior to data cutoff, dropout, or initiation of alternative anticancer therapy.
Time Frame
Prior to each treatment cycle, EOT (up to 24 weeks), monthly from the EOT assessment until the Day 181 assessment (only for CBC), at follow-up visits every 3 months for the next 24 months, and every 6 months thereafter (approximately 6 years)
Title
Time to Hematologic Remission
Description
Time to HR was defined as the time from the start of moxetumomab pasudotox administration to the first documentation of HR. HR was defined as the blood counts required for CR as normal CBC as exhibited by: Neutrophils >= 1.5 x 10^9/L, Platelets >= 100 x 10^9/L, and hemoglobin >= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.
Time Frame
Prior to each treatment cycle, EOT (up to 24 weeks), monthly from the EOT assessment until the Day 181 assessment (only for CBC), at follow-up visits every 3 months for the next 24 months, and every 6 months thereafter (approximately 6 years)
Title
Percentage of Participants With Objective Response (OR) Assessed by Blinded Independent Central Review
Description
The OR was defined as number of participants with a best response of CR or PR. CR requires all of following to be present: No evidence of leukemic cells in peripheral blood and/or by routine H/E staining of bone marrow; Resolution of any hepatomegaly, splenomegaly, and abnormal (>=2 cm minimum length) lymphadenopathy by CT or MRI (maximum diameter of spleen should be either <17 cm or have decreased by >25% from its baseline); normal CBC (Neutrophils >=1.5 x 10^9/L, Platelets >=100 x 10^9/L, and hemoglobin >=11.0 g/dL) without transfusions or growth factors for at least 4 weeks. PR requires all of following for a period of at least 4 weeks: >=50% decrease or normalization (<5.0 x 10^9/L) in peripheral blood lymphocyte count and >=50% reduction in lymphadenopathy and in abnormal haepatosplenomegaly by CT or MRI from pre-treatment baseline value; normal CBC as mentioned above or 50% improvement in CBC values over baseline without transfusions or growth factors for at least 4 weeks.
Time Frame
Prior to each treatment cycle, EOT (up to 24 weeks), monthly from the EOT assessment until the Day 181 assessment (only for CBC), at follow-up visits every 3 months for the next 24 months, and every 6 months thereafter (approximately 6 years)
Title
Percentage of Participants With Objective Response by Investigator's Assessment
Description
The OR was defined as number of participants with a best response of CR or PR. CR requires all of following to be present: No evidence of leukemic cells in peripheral blood and/or by routine H/E staining of bone marrow; Resolution of any hepatomegaly, splenomegaly, and abnormal (>=2 cm minimum length) lymphadenopathy by CT or MRI (maximum diameter of spleen should be either <17 cm or have decreased by >25% from its baseline); normal CBC (Neutrophils >=1.5 x 10^9/L, Platelets >=100 x 10^9/L, and hemoglobin >=11.0 g/dL) without transfusions or growth factors for at least 4 weeks. PR requires all of following for a period of at least 4 weeks: >=50% decrease or normalization (<5.0 x 10^9/L) in peripheral blood lymphocyte count and >=50% reduction in lymphadenopathy and in abnormal haepatosplenomegaly by CT or MRI from pre-treatment baseline value; normal CBC as mentioned above or 50% improvement in CBC values over baseline without transfusions or growth factors for at least 4 weeks.
Time Frame
Prior to each treatment cycle, end of treatment, and at follow-up visits every 3 months for the next 24 months and every 6 months thereafter (Approximately 6 years)
Title
Time to Objective Response Assessed by Blinded Independent Central Review
Description
Time to OR was defined as the time from the start of moxetumomab pasudotox administration to the first documentation of OR (CR or PR).
Time Frame
Prior to each treatment cycle, EOT (up to 24 weeks), monthly from the EOT assessment until the Day 181 assessment (only for CBC), at follow-up visits every 3 months for the next 24 months, and every 6 months thereafter (approximately 6 years)
Title
Duration of Objective Response Assessed by Blinded Independent Central Review
Description
Duration of OR was defined as the time from the first documentation of objective response (CR or PR) to the date of relapse. Duration of OR was censored on the date of last disease assessment or hematologic assessment for participants who have no documented relapse prior to data cut-off, dropout, or the initiation of alternative anticancer therapy.
Time Frame
Prior to each treatment cycle, EOT (up to 24 weeks), monthly from the EOT assessment until the Day 181 assessment (only for CBC), at follow-up visits every 3 months for the next 24 months, and every 6 months thereafter (approximately 6 years)
Title
Progression-free Survival (PFS) Assessed by Blinded Independent Central Review
Description
The PFS was defined as the time from the start of moxetumomab pasudotox administration to the earliest date of a disease assessment showing a progressive disease/relapse, earliest date of hematologic relapse or date of death, whichever was earlier. The PFS was censored on the date of last disease assessment or hematologic assessment for participants who are alive with no documented relapse or PD prior to data cut-off, dropout, or the initiation of alternative anticancer therapy.
Time Frame
Prior to each treatment cycle, EOT (up to 24 weeks), monthly from the EOT assessment until the Day 181 assessment (only for CBC), at follow-up visits every 3 months for the next 24 months, and every 6 months thereafter (approximately 6 years)
Title
Time to Treatment Failure (TTF) Assessed by Blinded Independent Central Review
Description
The TTF was defined as the time from the start of moxetumomab pasudotox administration to the date of the first of relapse, progressive disease, initiation of alternative anticancer therapy, or death due to disease or disease-related complication. The TTF was censored on the date of last disease assessment or hematologic assessment for participants who are alive with no documented relapse or PD prior to data cut-off, dropout, or the initiation of alternative anticancer therapy and also censored for death not accompanied by relapse.
Time Frame
Prior to each treatment cycle, EOT (up to 24 weeks), monthly from the EOT assessment until the Day 181 assessment (only for CBC), at follow-up visits every 3 months for the next 24 months, and every 6 months thereafter (approximately 6 years)
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Description
An Adverse Event (AE) is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. A serious adverse event (SAE) is an AE that results in death, initial or prolonged inpatient hospitalization, life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, or an important medical event. TEAEs and TESAEs are defined as AEs and SAEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug.
Time Frame
From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months)
Title
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs
Description
An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 30 days after the last dose of study drug (approximately 7 months).
Time Frame
From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months)
Title
Number of Participants With Abnormal Vital Signs Reported as TEAEs
Description
An abnormal vital signs that were judged by the investigator to be medically significant were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 30 days after the last dose of study drug (approximately 7 months).
Time Frame
From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months)
Title
Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs
Description
An abnormal ECG findings that were judged by the investigator to be medically significant were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 30 days after the last dose of study drug (approximately 7 months).
Time Frame
From the start of study treatment (Day 1) through 4-6 weeks after last dose of Cycle 6 (28-day cycle) (approximately 7 months)
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox
Description
The Tmax of moxetumomab pasudotox is reported.
Time Frame
Cycle 1 Day 1 (pre-dose; 5 mins and 3 hr post dose); Cycle 1 Day 5 (pre-dose; 5 mins, 1 hr, 3 hr, and 6 hrs post dose); and Cycle 2 Day 1 (pre-dose; 5 mins and 3 hr post dose)
Title
Maximum Observed Plasma Concentration (Cmax) of Moxetumomab Pasudotox
Description
The Cmax of moxetumomab pasudotox is reported.
Time Frame
Cycle 1 Day 1 (pre-dose; 5 mins and 3 hr post dose); Cycle 1 Day 5 (pre-dose; 5 mins, 1 hr, 3 hr, and 6 hrs post dose); and Cycle 2 Day 1 (pre-dose; 5 mins and 3 hr post dose)
Title
Time of Last (Tlast) Measurable Concentration of Moxetumomab Pasudotox
Description
The Tlast of moxetumomab pasudotox is reported.
Time Frame
Cycle 1 Day 1 (pre-dose; 5 mins and 3 hr post dose); Cycle 1 Day 5 (pre-dose; 5 mins, 1 hr, 3 hr, and 6 hrs post dose); and Cycle 2 Day 1 (pre-dose; 5 mins and 3 hr post dose)
Title
Area Under the Plasma Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC0-last) of Moxetumomab Pasudotox
Description
The AUC0-last of moxetumomab pasudotox is reported.
Time Frame
Cycle 1 Day 1 (pre-dose; 5 mins and 3 hr post dose); Cycle 1 Day 5 (pre-dose; 5 mins, 1 hr, 3 hr, and 6 hrs post dose); and Cycle 2 Day 1 (pre-dose; 5 mins and 3 hr post dose)
Title
Area Under the Plasma Concentration-time Curve From Time Zero to 3 Hours (AUC0-3hr) Post End of Moxetumomab Pasudotox
Description
The AUC0-3hr of moxetumomab pasudotox is reported.
Time Frame
Cycle 1 Day 1 (pre-dose; 5 mins and 3 hr post dose); Cycle 1 Day 5 (pre-dose; 5 mins, 1 hr, and 3 hr post dose); and Cycle 2 Day 1 (pre-dose; 5 mins and 3 hr post dose)
Title
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Moxetumomab Pasudotox
Description
The AUC0-inf of moxetumomab pasudotox is reported.
Time Frame
Cycle 1 Day 1 (pre-dose; 5 mins and 3 hr post dose); Cycle 1 Day 5 (pre-dose; 5 mins, 1 hr, 3 hr, and 6 hrs post dose); and Cycle 2 Day 1 (pre-dose; 5 mins and 3 hr post dose)
Title
Area Under the Plasma Concentration-time Curve Extrapolated (AUCExt) of Moxetumomab Pasudotox
Description
The AUCExt of moxetumomab pasudotox is reported.
Time Frame
Cycle 1 Day 1 (pre-dose; 5 mins and 3 hr post dose); Cycle 1 Day 5 (pre-dose; 5 mins, 1 hr, 3 hr, and 6 hrs post dose); and Cycle 2 Day 1 (pre-dose; 5 mins and 3 hr post dose)
Title
Systemic Clearance (CL) of Moxetumomab Pasudotox
Description
The CL of moxetumomab pasudotox is reported.
Time Frame
Cycle 1 Day 1 (pre-dose; 5 mins and 3 hr post dose); Cycle 1 Day 5 (pre-dose; 5 mins, 1 hr, 3 hr, and 6 hrs post dose); and Cycle 2 Day 1 (pre-dose; 5 mins and 3 hr post dose)
Title
Terminal Half Life (t1/2) of Moxetumomab Pasudotox
Description
The t1/2 of moxetumomab pasudotox is reported.
Time Frame
Cycle 1 Day 1 (pre-dose; 5 mins and 3 hr post dose); Cycle 1 Day 5 (pre-dose; 5 mins, 1 hr, 3 hr, and 6 hrs post dose); and Cycle 2 Day 1 (pre-dose; 5 mins and 3 hr post dose)
Title
Percentage of Participants With Positive Anti-drug Antibodies (ADA), Neutralizing Anti-drug Antibodies (nAb) and Specificity (CD22 and PE38) Positive to Moxetumomab Pasudotox
Description
Participants with ADA positive, nAb positive, cluster of differentiation 22 (CD22) positive of ADA positive/NAb positive, and pseudomonas exotoxin 38 (PE38) positive of ADA positive/NAb positive to moxetumomab pasudotox at any visit are reported.
Time Frame
Pre-infusion on Day 1 of Cycles 1, 2, 3, and 5; at the End of Treatment (4 to 6 weeks after the last dose; approximately 7 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA: Patients must have histologically confirmed hairy cell leukemia or hairy cell leukemia variant .with a need for therapy Patients must be Pseudomonas-immunotoxin naive Patients must have had at least 2 prior purine analogs, or at least 1 course of purine analog and 1 of either rituximab or BRAF inhibitor. Men or women age greater than or equal to 18 years. ECOG performance status less than or equal to 2. Patients must have adequate organ function EXCLUSION CRITERIA Patients who have had chemotherapy, immunotherapy or radiotherapy within 4 weeks prior to entering the study. Patients who are receiving any other investigational agents. Patients with known brain metastases should be excluded from this clinical trial Patients with clinically significant ophthalmologic findings during screening Pregnant or breastfeeding females. Positive for Hepatitis B core antibody or surface antigen unless the patient is on Lamivudine or Entecavir and Hepatitis B Viral DNA load is less than 2000 IU/mL. Active second malignancy requiring treatment other than minor resection of indolent cancers like basal cell and squamous skin cancers HIV-positive patients unless taking appropriate anti-HIV medications with a CD4 count of greater than 200. History of allogeneic bone marrow transplant. Patients with history of both thromboembolism and known congenital hypercoagulable conditions. Uncontrolled pulmonary infection, pulmonary edema. Adequate oxygen saturation Radioimmunotherapy within 2 years prior to enrollment in study. Adequate hematologic function Adequate lung function Patients with history of thrombotic microangiopathy or thrombotic microangiopathy / hemolytic uremic syndrome Patients with QTc interval (Friderica) elevation > 500 msec based on at least 2 separate 12-lead ECGs Patient on high dose estrogen Patients with clinical evidence of disseminated intravascular coagulation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MedImmune LLC
Organizational Affiliation
MedImmune LLC
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Research Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Research Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Research Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Research Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Research Site
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
Research Site
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Research Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Research Site
City
Antwerp
ZIP/Postal Code
2060
Country
Belgium
Facility Name
Research Site
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Research Site
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2G7
Country
Canada
Facility Name
Research Site
City
Brno
ZIP/Postal Code
625 00
Country
Czechia
Facility Name
Research Site
City
Caen
ZIP/Postal Code
14033
Country
France
Facility Name
Research Site
City
Le Chesnay Cedex
ZIP/Postal Code
78157
Country
France
Facility Name
Research Site
City
Pessac Cedex
ZIP/Postal Code
33604
Country
France
Facility Name
Research Site
City
Pierre-Bénite
ZIP/Postal Code
69310
Country
France
Facility Name
Research Site
City
Rouen Cedex 1
ZIP/Postal Code
76038
Country
France
Facility Name
Research Site
City
Strasbourg Cedex
ZIP/Postal Code
67098
Country
France
Facility Name
Research Site
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Research Site
City
Giessen
ZIP/Postal Code
35392
Country
Germany
Facility Name
Research Site
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Research Site
City
Dublin
ZIP/Postal Code
DUBLIN 8
Country
Ireland
Facility Name
Research Site
City
Haifa
ZIP/Postal Code
31048
Country
Israel
Facility Name
Research Site
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Research Site
City
Genova
ZIP/Postal Code
16132
Country
Italy
Facility Name
Research Site
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
Research Site
City
Siena
ZIP/Postal Code
53100
Country
Italy
Facility Name
Research Site
City
Bergen
ZIP/Postal Code
5099
Country
Norway
Facility Name
Research Site
City
Gdańsk
ZIP/Postal Code
80-952
Country
Poland
Facility Name
Research Site
City
Łódź
ZIP/Postal Code
93-510
Country
Poland
Facility Name
Research Site
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Research Site
City
Sutton
ZIP/Postal Code
SM2 5PT
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
7820038
Citation
Bouroncle BA. Thirty-five years in the progress of hairy cell leukemia. Leuk Lymphoma. 1994;14 Suppl 1:1-12.
Results Reference
background
PubMed Identifier
17237035
Citation
Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66. doi: 10.3322/canjclin.57.1.43.
Results Reference
background
PubMed Identifier
16990105
Citation
Sharpe RW, Bethel KJ. Hairy cell leukemia: diagnostic pathology. Hematol Oncol Clin North Am. 2006 Oct;20(5):1023-49. doi: 10.1016/j.hoc.2006.06.010.
Results Reference
background
PubMed Identifier
22355053
Citation
Kreitman RJ, Tallman MS, Robak T, Coutre S, Wilson WH, Stetler-Stevenson M, Fitzgerald DJ, Lechleider R, Pastan I. Phase I trial of anti-CD22 recombinant immunotoxin moxetumomab pasudotox (CAT-8015 or HA22) in patients with hairy cell leukemia. J Clin Oncol. 2012 May 20;30(15):1822-8. doi: 10.1200/JCO.2011.38.1756. Epub 2012 Feb 21.
Results Reference
background
PubMed Identifier
30030507
Citation
Kreitman RJ, Dearden C, Zinzani PL, Delgado J, Karlin L, Robak T, Gladstone DE, le Coutre P, Dietrich S, Gotic M, Larratt L, Offner F, Schiller G, Swords R, Bacon L, Bocchia M, Bouabdallah K, Breems DA, Cortelezzi A, Dinner S, Doubek M, Gjertsen BT, Gobbi M, Hellmann A, Lepretre S, Maloisel F, Ravandi F, Rousselot P, Rummel M, Siddiqi T, Tadmor T, Troussard X, Yi CA, Saglio G, Roboz GJ, Balic K, Standifer N, He P, Marshall S, Wilson W, Pastan I, Yao NS, Giles F. Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia. Leukemia. 2018 Aug;32(8):1768-1777. doi: 10.1038/s41375-018-0210-1. Epub 2018 Jul 20.
Results Reference
background
PubMed Identifier
33627164
Citation
Kreitman RJ, Dearden C, Zinzani PL, Delgado J, Robak T, le Coutre PD, Gjertsen BT, Troussard X, Roboz GJ, Karlin L, Gladstone DE, Kuptsova-Clarkson N, Liu S, Patel P, Rotolo F, Mitry E, Pastan I, Giles F; Study 1053 investigators. Moxetumomab pasudotox in heavily pre-treated patients with relapsed/refractory hairy cell leukemia (HCL): long-term follow-up from the pivotal trial. J Hematol Oncol. 2021 Feb 24;14(1):35. doi: 10.1186/s13045-020-01004-y.
Results Reference
derived
PubMed Identifier
31298972
Citation
Abou Dalle I, Ravandi F. Moxetumomab pasudotox for the treatment of relapsed and/or refractory hairy cell leukemia. Expert Rev Hematol. 2019 Sep;12(9):707-714. doi: 10.1080/17474086.2019.1643231. Epub 2019 Aug 1.
Results Reference
derived
Links:
URL
http://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2013-C-0106.html
Description
NIH Clinical Center Detailed Web Page
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=3161&filename=CD-ON-CAT-8015-1053_current_SAP_redacted_PDF-A.pdf
Description
130106_(CD-ON-CAT-8015-1053)_current_SAP_redacted_PDF-A
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=3161&filename=protocol-cd-on-cat-8015-1053-amendment-9_redacted_PDF-A.pdf
Description
Protocol-cd-on-cat-8015-1053-amendment-9_redacted_PDF-A

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Moxetumomab Pasudotox for Advanced Hairy Cell Leukemia

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