Back to resultsSafety Study of CAT-8015 to Treat Advanced B-cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (NHL or CLL)
Primary Purpose
Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
CAT-8015 20 mcg/kg
CAT-8015 30 mcg/kg
CAT-8015 40 mcg/kg
CAT-8015 50 mcg/kg
CAT-8015 60 mcg/kg
Sponsored by
About this trial
This is an interventional treatment trial for Non-Hodgkin Lymphoma focused on measuring NHL, CLL
Eligibility Criteria
Inclusion Criteria:
- Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization
- Participants must have histologically confirmed B-cell CLL, including small lymphocytic lymphoma (SLL), DLBCL, MCL, or FL
- B-cell NHL: a) Have previous confirmation of B-cell NHL b) Participants with DLBCL or MCL, must have relapsed or refractory disease after at least one prior regimen containing rituximab, either alone or in combination, and be ineligible for any available standard line of therapy known to be life-prolonging or life-saving c) Participants with FL, must have relapsed or refractory disease after at least two prior regimens, one of which included rituximab, either alone or in combination, and be ineligible for any available standard line of therapy known to be life-prolonging or life-saving d) Have measurable disease (at least one lesion greater than or equal to (≥) 20 millimeter (mm) in one dimension or ≥ 15 mm in two dimensions as measured by conventional or high resolution [spiral] computed tomography e) Not be a candidate for a hematopoietic stem cell (HSC) or bone marrow transplant
- B-cell CLL: a) Have previous confirmation of B-cell CLL with a characteristic immunophenotype by flow cytometry b) Have relapsed or refractory disease after at least 2 prior lines of treatment, at least 1 of which must have contained rituximab and be ineligible for any available standard line of therapy known to be life-prolonging or life-saving c) Not be a candidate for an HSC or BM transplant d) Have symptomatic disease that requires treatment
- Karnofsky Performance Status ≥ 70
- Life expectancy of ≥ 12 weeks
- Toxicities from previous cancer therapies must have recovered to Grade less than (<) 2
- Adequate hematological function defined as: a) Hemoglobin ≥ 9 g/dL b) Absolute neutrophil count ≥ 1500/mm^3 c) Platelet count ≥ 75,000/mm^3
- Prothrombin time-International Normalized Ratio/Partial thromboplastin time less than or equal to (≤) 1.5 × upper limit of normal (ULN), or for participants on anticoagulation therapy, status within therapeutic range
- Women of non-child-bearing potential or using effective contraception
- Male participants with partners of child-bearing potential must be surgically sterile or use a contraceptive method
Exclusion Criteria:
- Any available standard line of therapy known to be life-prolonging or life-saving
- Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic, or hormonal therapy for treatment of cancer
- For CLL participants only, rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy
- History of allergy or reaction to any component of the CAT-8015
- Receipt of any chemotherapy or small molecule targeted therapy or any biological- or immunological-based therapies for leukemia or lymphoma within 6 weeks
- Prior radiation therapy will not be excluded, providing the volume of bone marrow treated is less than 25 percent
- Any history of prior pseudomonas-exotoxin immunotoxin administration including CAT-8015, CAT-3888, or LMB-2
- History of other invasive malignancy within 5 years, with some exceptions
- Evidence of significant active infection requiring antimicrobial, antifungal, antiparasitic or antiviral therapy or for which other supportive care is given
- Autologous stem cell transplantation within 6 months prior to study entry
- Allogenic stem cell transplantation or any other organ transplant
- HIV-positive or AIDS, Hepatitis B or hepatitis C infection as defined by seropositive for hepatitis B (HBsAg) or hepatitis C and elevated liver transaminases
- Use of immunosuppressive medication other than steroids within 7 days, use of systemic steroids within 7 days before the first dose of CAT-8015 (inhaled and topical corticosteroids are permitted). Participants may take replacement doses of steroids (defined as ≤ 30 mg/day hydrocortisone or the equivalent) if on a stable dose for at least 2 weeks prior to the first dose of CAT-8015
- Documented current central nervous system involvement by leukemia or lymphoma
- Pregnancy or lactation, other severe, concurrent diseases
- Concurrent enrollment in another clinical study
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
CAT-8015 20 microgram per kilogram (mcg/kg)
CAT-8015 30 mcg/kg
CAT-8015 40 mcg/kg
CAT-8015 50 mcg/kg
CAT-8015 60 mcg/kg
Arm Description
Participants will receive 20 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg.
Participants will receive 30 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg.
Participants will receive 40 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg.
Participants will receive 50 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg.
Participants will receive 60 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg.
Outcomes
Primary Outcome Measures
Maximum Tolerated Dose (MTD)
MTD reflects highest dose of drug that did not cause an unacceptable side effect (= Dose Limiting Toxicity [DLT]) in more than 30 percent (%) of participants.
Number of Participants With Dose Limiting Toxicities (DLTs)
Any Grade 3 or greater, non-hematological toxicity (including capillary leak syndrome [CLS] and thrombotic microangiopathy/ hemolytic uremic syndrome (HUS), Grade 3 or higher treatment-related hematologic toxicities and only ≥ Grade 3 thrombotic microangiopathy /HUS constituted a DLT with few exceptions.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An Serious Adverse Event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Number of Participants With Electrocardiogram (ECG) Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Secondary Outcome Measures
Percentage of Participants With Complete Response (CR)
The CR rate was defined as the percentage of participants who had achieved CR based on both the evaluable population for efficacy.
Duration of Complete Response
Duration of CR was measured from the first documentation of a CR to the time of relapse for the subgroup of participants with CR. Duration of CR was calculated using the Kaplan Meier method. The Evaluable Population for efficacy was used to evaluate the endpoints for the efficacy profile.
Percentage of Participants With Partial Response (PR)
Percentage of Participants With Objective Response (OR)
OR was defined as the percentage of participants with CR or partial response (PR).
Time to Response (TTR)
TTR was measured from the start of moxetumomab pasudotox administration to the first documentation of response (CR or PR) and was only assessed in participants who had achieved objective response (OR).
Duration of Objective Response (DOR)
DOR was measured from the first documentation of OR to the event of relapse. DOR was calculated using the Kaplan-Meier method.
Duration of Stable Disease (SD)
Duration of SD was defined as the time period from start of moxetumomab pasudotox administration to the event of progressive disease (PD)/relapse. Duration of SD was only calculated for the subgroup of participants with best response of CR, PR, or SD, and was calculated using the Kaplan-Meier method.
Maximum Plasma Concentration (Cmax) of Moxetumomab Pasudotox
Maximum observed drug concentration of Moxetumomab pasudotox in plasma.
Area Under Concentration-Time Curve From Dosing Extrapolated to Infinity (AUCinf) of Moxetumomab Pasudotox
Area under the concentration versus time curve from zero to infinity (AUC) of Moxetumomab pasudotox in Plasma.
Clearance (CL) of Moxetumomab Pasudotox
CL of drug is rate at which drug is metabolized or eliminated by normal biological processes and is influenced by fraction of dose absorbed.
Elimination Half Life (t1/2) of Moxetumomab Pasudotox
Plasma decay half life is the time measured for the plasma concentration to decrease by one half.
Number of Participants With Positive Anti-Drug Antibody
The moxetumomab pasudotox specific bridging assay using the Meso Scale Discovery platform was employed to detect anti-drug antibodies (ADA).
Number of Participants With CD22 Expression Levels
CD22 Expression was analyzed using Prism® analysis. Flow cytometry was performed to quantitate the CD22 expression for the purpose of evaluating the relationship of CD22 expression with response to treatment.
Number of Capillary Leak Syndrome (CLS) Participants With Weight Changes, Albumin, Hypotension, Edema, Hypoxia, and Pulmonary Adverse Events (AEs)
The correlation of CLS and weight changes, albumin, hypotension, edema, hypoxia, and pulmonary AEs were examined.
Percentage of Participants With Stable Disease (SD)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01030536
Brief Title
Safety Study of CAT-8015 to Treat Advanced B-cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (NHL or CLL)
Official Title
A Phase 1/2 Study of CAT-8015 in Adult Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
February 15, 2010 (Actual)
Primary Completion Date
March 4, 2013 (Actual)
Study Completion Date
March 4, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MedImmune LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objectives of this study are to determine the maximum tolerated dose (MTD) or optimal biologic dose (OBD) and safety profile of CAT-8015 in participants with relapsed or refractory advanced B-cell NHL (diffuse large B-cell lymphoma [DLBCL], follicular lymphoma [FL], mantle cell lymphoma [MCL]) or CLL.
Detailed Description
To determine the maximum tolerated dose (MTD) or optimal biologic dose (OBD) of CAT-8015 in participants with relapsed or refractory advanced B-cell NHL (DLBCL, FL, MCL) or CLL.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia
Keywords
NHL, CLL
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
23 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CAT-8015 20 microgram per kilogram (mcg/kg)
Arm Type
Experimental
Arm Description
Participants will receive 20 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg.
Arm Title
CAT-8015 30 mcg/kg
Arm Type
Experimental
Arm Description
Participants will receive 30 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg.
Arm Title
CAT-8015 40 mcg/kg
Arm Type
Experimental
Arm Description
Participants will receive 40 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg.
Arm Title
CAT-8015 50 mcg/kg
Arm Type
Experimental
Arm Description
Participants will receive 50 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg.
Arm Title
CAT-8015 60 mcg/kg
Arm Type
Experimental
Arm Description
Participants will receive 60 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle. Dose escalation is to be continued to the Maximum tolerated dose (MTD) or Optimal biologic dose (OBD). Subsequent dose levels with a 10 mcg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 mcg/kg.
Intervention Type
Drug
Intervention Name(s)
CAT-8015 20 mcg/kg
Intervention Description
Participants will receive 20 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
CAT-8015 30 mcg/kg
Intervention Description
Participants will receive 30 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
CAT-8015 40 mcg/kg
Intervention Description
Participants will receive 40 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
CAT-8015 50 mcg/kg
Intervention Description
Participants will receive 50 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
CAT-8015 60 mcg/kg
Intervention Description
Participants will receive 60 mcg/kg Moxetumomab pasudotox (CAT-8015) as an intravenous (IV) infusion over 30 minutes on Days 1, 3, and 5 of every 28-day cycle.
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD)
Description
MTD reflects highest dose of drug that did not cause an unacceptable side effect (= Dose Limiting Toxicity [DLT]) in more than 30 percent (%) of participants.
Time Frame
Day 1 to end of Cycle 1 (approximately 28 days)
Title
Number of Participants With Dose Limiting Toxicities (DLTs)
Description
Any Grade 3 or greater, non-hematological toxicity (including capillary leak syndrome [CLS] and thrombotic microangiopathy/ hemolytic uremic syndrome (HUS), Grade 3 or higher treatment-related hematologic toxicities and only ≥ Grade 3 thrombotic microangiopathy /HUS constituted a DLT with few exceptions.
Time Frame
Day 1 to end of Cycle 1 (approximately 28 days)
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Description
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An Serious Adverse Event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Time Frame
From Screening (Day -28) to Post Therapy Day 30
Title
Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
Description
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Time Frame
From Screening (Day -28) to Post Therapy Day 30
Title
Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
Description
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Time Frame
From Screening (Day -28) to Post Therapy Day 30
Title
Number of Participants With Electrocardiogram (ECG) Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
Description
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Time Frame
From Screening (Day -28) to Post Therapy Day 30
Secondary Outcome Measure Information:
Title
Percentage of Participants With Complete Response (CR)
Description
The CR rate was defined as the percentage of participants who had achieved CR based on both the evaluable population for efficacy.
Time Frame
Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Title
Duration of Complete Response
Description
Duration of CR was measured from the first documentation of a CR to the time of relapse for the subgroup of participants with CR. Duration of CR was calculated using the Kaplan Meier method. The Evaluable Population for efficacy was used to evaluate the endpoints for the efficacy profile.
Time Frame
Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Title
Percentage of Participants With Partial Response (PR)
Time Frame
Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Title
Percentage of Participants With Objective Response (OR)
Description
OR was defined as the percentage of participants with CR or partial response (PR).
Time Frame
Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Title
Time to Response (TTR)
Description
TTR was measured from the start of moxetumomab pasudotox administration to the first documentation of response (CR or PR) and was only assessed in participants who had achieved objective response (OR).
Time Frame
Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Title
Duration of Objective Response (DOR)
Description
DOR was measured from the first documentation of OR to the event of relapse. DOR was calculated using the Kaplan-Meier method.
Time Frame
Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Title
Duration of Stable Disease (SD)
Description
Duration of SD was defined as the time period from start of moxetumomab pasudotox administration to the event of progressive disease (PD)/relapse. Duration of SD was only calculated for the subgroup of participants with best response of CR, PR, or SD, and was calculated using the Kaplan-Meier method.
Time Frame
Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
Title
Maximum Plasma Concentration (Cmax) of Moxetumomab Pasudotox
Description
Maximum observed drug concentration of Moxetumomab pasudotox in plasma.
Time Frame
Pre-dose and End of infusion on Day 1, 3 and 5 of each cycle; 1, 3 and 6 hour after the end of infusion on Day 1 of each cycle
Title
Area Under Concentration-Time Curve From Dosing Extrapolated to Infinity (AUCinf) of Moxetumomab Pasudotox
Description
Area under the concentration versus time curve from zero to infinity (AUC) of Moxetumomab pasudotox in Plasma.
Time Frame
Pre-dose and End of infusion on Day 1, 3 and 5 of each cycle; 1, 3 and 6 hour after the end of infusion on Day 1 of each cycle
Title
Clearance (CL) of Moxetumomab Pasudotox
Description
CL of drug is rate at which drug is metabolized or eliminated by normal biological processes and is influenced by fraction of dose absorbed.
Time Frame
Pre-dose and End of infusion on Day 1, 3 and 5 of each cycle; 1, 3 and 6 hour after the end of infusion on Day 1 of each cycle
Title
Elimination Half Life (t1/2) of Moxetumomab Pasudotox
Description
Plasma decay half life is the time measured for the plasma concentration to decrease by one half.
Time Frame
Pre-dose and End of infusion on Day 1, 3 and 5 of each cycle; 1, 3 and 6 hour after the end of infusion on Day 1 of each cycle
Title
Number of Participants With Positive Anti-Drug Antibody
Description
The moxetumomab pasudotox specific bridging assay using the Meso Scale Discovery platform was employed to detect anti-drug antibodies (ADA).
Time Frame
Baseline (Day 1) up to End of the Treatment (Last dose of Last cycle) (approximately 3 years)
Title
Number of Participants With CD22 Expression Levels
Description
CD22 Expression was analyzed using Prism® analysis. Flow cytometry was performed to quantitate the CD22 expression for the purpose of evaluating the relationship of CD22 expression with response to treatment.
Time Frame
Baseline (Day 1) up to End of the Treatment (Last dose of Last cycle) (approximately 3 years)
Title
Number of Capillary Leak Syndrome (CLS) Participants With Weight Changes, Albumin, Hypotension, Edema, Hypoxia, and Pulmonary Adverse Events (AEs)
Description
The correlation of CLS and weight changes, albumin, hypotension, edema, hypoxia, and pulmonary AEs were examined.
Time Frame
From Screening (Day -28) to Post Therapy Day 30
Title
Percentage of Participants With Stable Disease (SD)
Time Frame
Baseline (Day 1) until Final Study Visit Post Therapy (up to 2 year after the last participant begins study drug treatment)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization
Participants must have histologically confirmed B-cell CLL, including small lymphocytic lymphoma (SLL), DLBCL, MCL, or FL
B-cell NHL: a) Have previous confirmation of B-cell NHL b) Participants with DLBCL or MCL, must have relapsed or refractory disease after at least one prior regimen containing rituximab, either alone or in combination, and be ineligible for any available standard line of therapy known to be life-prolonging or life-saving c) Participants with FL, must have relapsed or refractory disease after at least two prior regimens, one of which included rituximab, either alone or in combination, and be ineligible for any available standard line of therapy known to be life-prolonging or life-saving d) Have measurable disease (at least one lesion greater than or equal to (≥) 20 millimeter (mm) in one dimension or ≥ 15 mm in two dimensions as measured by conventional or high resolution [spiral] computed tomography e) Not be a candidate for a hematopoietic stem cell (HSC) or bone marrow transplant
B-cell CLL: a) Have previous confirmation of B-cell CLL with a characteristic immunophenotype by flow cytometry b) Have relapsed or refractory disease after at least 2 prior lines of treatment, at least 1 of which must have contained rituximab and be ineligible for any available standard line of therapy known to be life-prolonging or life-saving c) Not be a candidate for an HSC or BM transplant d) Have symptomatic disease that requires treatment
Karnofsky Performance Status ≥ 70
Life expectancy of ≥ 12 weeks
Toxicities from previous cancer therapies must have recovered to Grade less than (<) 2
Adequate hematological function defined as: a) Hemoglobin ≥ 9 g/dL b) Absolute neutrophil count ≥ 1500/mm^3 c) Platelet count ≥ 75,000/mm^3
Prothrombin time-International Normalized Ratio/Partial thromboplastin time less than or equal to (≤) 1.5 × upper limit of normal (ULN), or for participants on anticoagulation therapy, status within therapeutic range
Women of non-child-bearing potential or using effective contraception
Male participants with partners of child-bearing potential must be surgically sterile or use a contraceptive method
Exclusion Criteria:
Any available standard line of therapy known to be life-prolonging or life-saving
Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic, or hormonal therapy for treatment of cancer
For CLL participants only, rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy
History of allergy or reaction to any component of the CAT-8015
Receipt of any chemotherapy or small molecule targeted therapy or any biological- or immunological-based therapies for leukemia or lymphoma within 6 weeks
Prior radiation therapy will not be excluded, providing the volume of bone marrow treated is less than 25 percent
Any history of prior pseudomonas-exotoxin immunotoxin administration including CAT-8015, CAT-3888, or LMB-2
History of other invasive malignancy within 5 years, with some exceptions
Evidence of significant active infection requiring antimicrobial, antifungal, antiparasitic or antiviral therapy or for which other supportive care is given
Autologous stem cell transplantation within 6 months prior to study entry
Allogenic stem cell transplantation or any other organ transplant
HIV-positive or AIDS, Hepatitis B or hepatitis C infection as defined by seropositive for hepatitis B (HBsAg) or hepatitis C and elevated liver transaminases
Use of immunosuppressive medication other than steroids within 7 days, use of systemic steroids within 7 days before the first dose of CAT-8015 (inhaled and topical corticosteroids are permitted). Participants may take replacement doses of steroids (defined as ≤ 30 mg/day hydrocortisone or the equivalent) if on a stable dose for at least 2 weeks prior to the first dose of CAT-8015
Documented current central nervous system involvement by leukemia or lymphoma
Pregnancy or lactation, other severe, concurrent diseases
Concurrent enrollment in another clinical study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ramy Ibrahim, M.D.
Organizational Affiliation
MedImmune LLC
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Los Angeles
State/Province
California
Country
United States
Facility Name
Research Site
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Research Site
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
Research Site
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
Facility Name
Research Site
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29424
Country
United States
Facility Name
Research Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Research Site
City
Temple
State/Province
Texas
ZIP/Postal Code
76508
Country
United States
Facility Name
Research Site
City
Łódź
ZIP/Postal Code
93-510
Country
Poland
12. IPD Sharing Statement
Learn more about this trial
Safety Study of CAT-8015 to Treat Advanced B-cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia (NHL or CLL)
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