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A Study Of Two Inotuzumab Ozogamicin Doses in Relapsed/ Refractory Acute Lymphoblastic Leukemia Transplant Eligible Patients

Primary Purpose

Leukemia, Precursor b-Cell Lymphoblastic Leukemia-Lymphoma, ACUTE LYMPHOBLASTIC LEUKEMIA

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
inotuzumab ozogamicin-dose level 2
Inotuzumab ozogamicin-dose level 1
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring Leukemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma, ACUTE LYMPHOBLASTIC leukemia, inotuzumab ozogamicin, Besponsa, transplant

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Relapsed or refractory precursor CD22 positive B cell ALL with M2 or M3 marrow (≥5% blasts) and who are eligible for HSCT;
  2. Have 1 or more of the following risk factors for developing VOD:

    1. Due to receive Salvage 2 or greater;
    2. Prior HSCT;
    3. Age ≥55 years.
    4. Ongoing or prior hepatic disease which may include a prior history of hepatitis or drug induced liver injury, as well as hepatic steatosis, nonalcoholic steatohepatitis, baseline elevations of bilirubin > upper limit of normal (ULN) and ≤1.5 x ULN.
  3. Ph+ ALL patients must have failed treatment with at least 1 second or third generation tyrosine kinase inhibitor and standard multi agent induction chemotherapy;
  4. Patients in Salvage 1 with late relapse should be deemed poor candidates for reinduction with initial therapy;
  5. Patients with lymphoblastic lymphoma and bone marrow involvement 5% lymphoblasts by morphologic assessment;
  6. Age 18 years to 75 years;
  7. Eastern Cooperative Oncology Group (ECOG) performance status 0 2;
  8. Adequate liver function, including total serum bilirubin ≤1.5 x ULN unless the patient has documented Gilbert syndrome, and aspartate and alanine aminotransferase (AST and ALT) ≤2.5 x ULN;
  9. Serum creatinine ≤1.5 x ULN or any serum creatinine level associated with a measured or calculated creatinine clearance of >=40 mL/min;
  10. Male and female patients of childbearing potential and at risk for pregnancy must agree to use a highly effective method of contraception throughout the study and for a minimum of 8 months (females) and 5 months (males) after the last dose of assigned treatment. A patient is of childbearing potential if, in the opinion of the Investigator, he/she is biologically capable of having children and is sexually active. Female subjects of nonchildbearing potential must meet at least 1 of the following criteria:

    1. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle stimulating hormone (FSH) level confirming the postmenopausal state;
    2. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
    3. Have medically confirmed ovarian failure. All other female subjects (including female subjects with tubal ligations) are considered to be of childbearing potential.
  11. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study; patients with mental capacity which requires the presence of a legally authorized representative will be excluded from the study;
  12. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

  1. Isolated extramedullary relapse (ie, testicular or central nervous system);
  2. Burkitt's or mixed phenotype acute leukemia based on the WHO 2008 criteria;
  3. Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS directed local treatment for active disease within the prior 28 days, symptomatic CNS leukemia (ie, cranial nerve palsies or other significant neurologic dysfunction) within 28 days. Prophylactic intrathecal medication is not a reason for exclusion;
  4. Prior chemotherapy within 2 weeks before randomization with the following exceptions:

    1. To reduce the circulating lymphoblast count or palliation: ie, steroids, hydroxyurea or vincristine;
    2. For ALL maintenance: mercaptopurine, methotrexate, vincristine, thioguanine, and/or tyrosine kinase inhibitors.

    Patients must have recovered from acute non hematologic toxicity (to Grade 1 or less) of all previous therapy prior to enrollment.

  5. Prior monoclonal antibodies within 6 weeks of randomization, with the exception of rituximab which must be discontinued at least 2 weeks prior to randomization;
  6. Prior inotuzumab ozogamicin treatment or other anti CD22 immunotherapy within 6 months before randomization;
  7. Prior allogeneic hematopoietic stem cell transplant (HSCT) within 90 days before randomization. Patients must have completed immunosuppression therapy for treatment of graft versus host disease (GvHD) prior to enrollment. At randomization, patients must not have Grade 2 or higher acute GvHD, or extensive chronic GvHD;
  8. Peripheral absolute lymphoblast count >=10,000 /L (treatment with hydroxyurea and/or steroids/vincristine is permitted within 2 weeks of randomization to reduce the white blood cell [WBC] count);
  9. Known systemic vasculitides (eg, Wegener's granulomatosis, polyarteritis nodosa, systemic lupus erythematosus), primary or secondary immunodeficiency (such as human immunodeficiency virus [HIV] infection or severe inflammatory disease);
  10. Active hepatitis B infection as evidenced by hepatitis B surface antigen, active hepatitis C infection (must be anti-hepatitis C antibody negative or hepatitis C ribonucleic acid negative), or known seropositivity for HIV. HIV testing may need to be performed in accordance with local regulations or local practice;
  11. Major surgery within 4 weeks before randomization;
  12. Unstable or severe uncontrolled medical condition (eg, unstable cardiac function or unstable pulmonary condition);
  13. Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ of the cervix, or localized prostate cancer that has been definitely treated with radiation or surgery. Patients with previous malignancies are eligible provided that they have been disease free for >=2 years;
  14. Patients with active heart disease or the presence of New York Heart Association (NYHA) stage III or IV congestive heart failure;
  15. QTcF >470 msec (based on the average of 3 consecutive electrocardiogram [ECGs]);
  16. Myocardial infarction within 6 months before randomization;
  17. History of clinically significant ventricular arrhythmia, or unexplained syncope not believed to be vasovagal in nature, or chronic bradycardic states such as sinoatrial block or higher degrees of atrioventricular (AV) block unless a permanent pacemaker has been implanted;
  18. Uncontrolled electrolyte disorders that can compound the effects of a QTc prolonging drug (eg, hypokalemia, hypocalcemia, hypomagnesemia);
  19. Prior confirmed or ongoing hepatic veno occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS), or other serious or current ongoing liver disease such as cirrhosis or nodular regenerative hyperplasia;
  20. Administration of live vaccine within 6 weeks before randomization;
  21. Evidence of uncontrolled current serious active infection (including sepsis, bacteremia, fungemia) or patients with a recent history (within 4 months) of deep tissue infections such as fascitis or osteomyelitis;
  22. Patients who have had a severe allergic reaction or anaphylactic reaction to any humanized monoclonal antibodies;
  23. Pregnant female subjects; breastfeeding female subjects; fertile male subjects and female subjects of childbearing potential who are unwilling or unable to use highly effective contraception as outlined in this protocol for the duration of the study and for a minimum of 8 months (females) and 5 months (males) after the last dose of investigational product;
  24. Investigative site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study;
  25. Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry and/or during study participation (up through the end of treatment visit);
  26. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.

Sites / Locations

  • Keck Hospital of USC
  • LAC+USC Medical Center
  • USC/Norris Comprehensive Cancer Center
  • Rush University Medical Center
  • University of Maryland- Greenebaum Comprehensive Cancer Center
  • Seattle Cancer Care Alliance
  • University of Washington Medical Center
  • Debreceni Egyetem Klinikai Központ, Orvosi Kepalkotó Klinika, Radiológia
  • Debreceni Egyetem Klinikai Központ, Pathológiai lntézet
  • Szabolcs-Szatmar Bereg Megyei Korhazak es Egyetemi Oktatokorhaz, Josa Andras Korhaz, Hematologia
  • Artemis hospital
  • Sahyadri Clinical Research and Development Centre
  • Sahyadri Super Speciality Hospital
  • Sahyadri Super Speciality Hospital Nagar Road
  • Sahyadri Super Speciality Hospital
  • Christian Medical College
  • Christian Medical College Vellore- Ranipet Campus
  • Klinika Hematologii i Transplantologii, Uniwersyteckie Centrum Kliniczne
  • Instytut Hematologii i Transfuzjologii
  • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza - Radeckiego we Wroclawiu
  • Apteka Centralna
  • National University Hospital
  • Raffles Hospital
  • Raffles Radiology
  • Hospital Universitario Central de Asturias
  • Hospital Universitari Vall d'Hebron
  • Hospital General Universitario Gregorio Maranon
  • Hospital Universitario Ramon y Cajal
  • Hospital General - Semisótano
  • Hospital Universitario Virgen del Rocio
  • Hospital Clinico Universitario de Valencia
  • Hospital Universitari i Politecnic La Fe
  • Changhua Christian Hospital
  • National Taiwan University Hospital
  • Anadolu Health Center Hospital
  • Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital Clinical Research Center
  • Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital Hematology Department
  • Ankara University Faculty of Medicine Cebeci Hospital Hematology Department
  • Private Medstar Antalya Hosp. Hematology and Stem Cell Transplantation Center
  • Marmara University Pendik Training and Research Hospital Hematology Unit
  • Ege University Medical Faculty
  • Dokuz Eylul University Medical Faculty
  • Medicalpark Izmir Hospital
  • Erciyes Universitesi Tip Fakultesi Hastaneleri
  • Ondokuz Mayis University Faculty Of Medicine Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Dose Level 2

Dose Level 1

Arm Description

Inotuzumab ozogamicin at starting dose 1.2 mg/m2/cycle (administered in 3 divided doses). Most patients expected to receive 2 or 3 cycles (cycle length 21 to 28 days)

Inotuzumab ozogamicin at starting dose 1.8 mg/m2/cycle (administered in 3 divided doses). Most patients expected to receive 2 or 3 cycles (cycle length 21 to 28 days)

Outcomes

Primary Outcome Measures

Percentage of Participants With Hematologic Remission (Complete Remission [CR]/Complete Remission With Incomplete Hematologic Recovery [CRi])
CR defined the disappearance of leukemia indicated by less than (<) 5 percent (%) marrow blasts & absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by absolute neutrophil count (ANC) greater than or equal to (≥)1000 per microliter (/μL) & platelets ≥100,000/μL. C1 extramedullary disease status (i.e. complete disappearance of measurable & non-measurable extramedullary disease with the following exceptions: for participants with at least 1 measurable lesion, all nodal masses greater than (>) 1.5 centimeters (cm) in greatest transverse diameter (GTD) at baseline must have regressed to less than or equal to (≤) 1.5 cm in GTD; all nodal masses ≥1 cm & ≤1.5 cm in GTD at baseline must have regressed to <1 cm GTD or reduced by 75% in sum of products of greatest diameters, no new lesions, spleen & other previously enlarged organs must have regressed in size & must not be palpable) was required. CRi defined as CR except ANC <1000/μL &/or platelets <100,000/μL.
Rate of veno-occlusive disease (VOD)
Defined as the percentage of participants with VOD. VOD was defined as one of the following (a) the occurrence of bilirubin >=2mg/dL with 2 or more of the following: painful hepatomegaly, weight gain >5%, or ascites, or (b) histologically proven VOD, or (c) 2 or more of the following with hemodynamic and /or ultrasound evidence of VOD: bilirubin >=2mg/dL, painful hepatomegaly, weight gain >5%, or ascites.

Secondary Outcome Measures

Frequency of adverse events
Adverse events to be reported during treatment and for at least 9 weeks after last dose. VOD reported for up to 2 years from randomization.
Minimal residual disease (MRD) negativity
MRD analysis performed at least once in participants with prior assessment of CR or CRi. Bone marrow aspirates, collected at screening and during the study to be sent to the central laboratory and analyzed using multiparametric flow cytometry. A peripheral blood sample to be provided if a participant had an inadequate bone marrow aspirate at screening. MRD negativity considered to be achieved if the lowest value of MRD from the first date of CR/CRi to EoT was <1 × 10^-4 lasts/nucleated cells.
Duration of remission (DoR) for Participants Who Achieved CR/CRi
DoR defined as time from date of first response in responders (CR/CRi) to date of progression or death
Progression free survival (PFS)
PFS defined as time from date of randomization to earliest date of the death or progressive disease
Overall survival (OS)
OS defined as the time from randomization to date of death due to any cause.
Rate of hematopoietic stem cell transplantation (HSCT)
HSCT rate defined as the percentage of participants who underwent HSCT following treatment with inotuzumab ozogamicin
Post HSCT relapse
Post HSCT relapse defined as the time from date of HSCT to the date of first relapse post HSCT.
Post HSCT mortality
Post HSCT mortality defined as the time from date of HSCT to the date of death due to any cause
Post HSCT non relapse mortality
Post HSCT non relapse mortality defined as time from date of HSCT to the date of death due to any cause without prior relapse/progression post HSCT
Post HSCT relapse related mortality
Post HSCT relapse related mortality defined as time from date of HSCT to the date of death due to any cause with prior relapse/progression post HSCT.
Pharmacokinetics, Cmax
Maximum observed drug concentration (end of the infusion)
Percentage of patients with positive anti-drug antibody response
Testing for anti-drug antibodies, including neutralizing antibodies
Percentage of patients with laboratory abnormalities (NCI CTCAE grade)
Magnesium, Calcium, Creatinine, Albumin, Alanine aminotransferase, Aspartate aminotransferase, Glucose, Phosphorus, Total Bilirubin, Blood urea nitrogen or urea, Uric acid or urate, Alkaline phosphatase, Lactate dehydrogenase, Gamma glutamyl transpeptidase, Total protein, Amylase and/or Lipase, Platelet Count, White Blood Cell Count (differential), hemoglobin, INR or prothrombin time, Activated partial thromboplastin time.
Pharmacokinetics, Ctrough
Drug concentration immediately prior to the next dose administration
Pharmacokinetics, Clearance
Volume of plasma cleared of drug per unit of time, calculated using non-linear mixed effects modeling
Pharmacokinetics, Area under the curve (AUC)
Calculated using non-linear mixed effects modeling

Full Information

First Posted
July 27, 2018
Last Updated
July 24, 2023
Sponsor
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT03677596
Brief Title
A Study Of Two Inotuzumab Ozogamicin Doses in Relapsed/ Refractory Acute Lymphoblastic Leukemia Transplant Eligible Patients
Official Title
A PHASE 4, OPEN-LABEL, RANDOMIZED STUDY OF TWO INOTUZUMAB OZOGAMICIN DOSE LEVELS IN ADULT PATIENTS WITH RELAPSED OR REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA ELIGIBLE FOR HEMATOPOIETIC STEM CELL TRANSPLANTATION AND WHO HAVE RISK FACTOR(S) FOR VENO-OCCLUSIVE DISEASE
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
July 1, 2019 (Actual)
Primary Completion Date
September 21, 2022 (Actual)
Study Completion Date
May 26, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study will explore 2 different doses of inotuzumab ozogamicin including the dose that is approved and a lower dose. The main purpose of this study is to evaluate whether a dose of inotuzumab ozogamicin, lower than the approved dose, could be recommended for adult patient with relapsed or refractory ALL who may be at higher risk for severe liver problems after inotuzumab ozogamicin treatment and stem cell transplant (a potentially curative therapy that can replace cancer cells with healthy cells). Efficacy and safety of the 2 doses will be evaluated.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Precursor b-Cell Lymphoblastic Leukemia-Lymphoma, ACUTE LYMPHOBLASTIC LEUKEMIA
Keywords
Leukemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma, ACUTE LYMPHOBLASTIC leukemia, inotuzumab ozogamicin, Besponsa, transplant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
The study will be conducted in 2 phases: a run in phase and a randomized phase. Run in phase: a total of up to 22 patients will be enrolled to receive the starting dose of 1.2 mg/m2/cycle (dose level 2). A Simon Two Stage optimal design will be used. If acceptable efficacy (CR/CRi and MRD negativity) is observed in the run in phase, the study will enter the randomized phase. Randomized phase: if acceptable efficacy is observed in the run in phase, the study will enter the randomized phase. A total of approximately 80 patients will be randomized (1:1) to 1 of 2 dose levels of inotuzumab ozogamicin (40 patients per dose level).
Masking
None (Open Label)
Allocation
Randomized
Enrollment
102 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dose Level 2
Arm Type
Experimental
Arm Description
Inotuzumab ozogamicin at starting dose 1.2 mg/m2/cycle (administered in 3 divided doses). Most patients expected to receive 2 or 3 cycles (cycle length 21 to 28 days)
Arm Title
Dose Level 1
Arm Type
Active Comparator
Arm Description
Inotuzumab ozogamicin at starting dose 1.8 mg/m2/cycle (administered in 3 divided doses). Most patients expected to receive 2 or 3 cycles (cycle length 21 to 28 days)
Intervention Type
Drug
Intervention Name(s)
inotuzumab ozogamicin-dose level 2
Other Intervention Name(s)
Besponsa
Intervention Description
Inotuzumab ozogamicin (BESPONSA™) is a CD22 targeted antibody drug conjugate (ADC) approved by US FDA for treatment of adults with relapsed or refractory B cell precursor acute lymphoblastic leukemia (ALL). The approved starting dose is 1.8mg/m2/cycle. This treatment arm evaluates a lower starting dose of 1.2mg/m2/cycle.
Intervention Type
Drug
Intervention Name(s)
Inotuzumab ozogamicin-dose level 1
Other Intervention Name(s)
Besponsa
Intervention Description
Inotuzumab ozogamicin (BESPONSA™) is a CD22 targeted antibody drug conjugate (ADC) approved by US FDA for treatment of adults with relapsed or refractory B cell precursor acute lymphoblastic leukemia (ALL). The approved starting dose of 1.8mg/m2/cycle is administered in this treatment arm.
Primary Outcome Measure Information:
Title
Percentage of Participants With Hematologic Remission (Complete Remission [CR]/Complete Remission With Incomplete Hematologic Recovery [CRi])
Description
CR defined the disappearance of leukemia indicated by less than (<) 5 percent (%) marrow blasts & absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by absolute neutrophil count (ANC) greater than or equal to (≥)1000 per microliter (/μL) & platelets ≥100,000/μL. C1 extramedullary disease status (i.e. complete disappearance of measurable & non-measurable extramedullary disease with the following exceptions: for participants with at least 1 measurable lesion, all nodal masses greater than (>) 1.5 centimeters (cm) in greatest transverse diameter (GTD) at baseline must have regressed to less than or equal to (≤) 1.5 cm in GTD; all nodal masses ≥1 cm & ≤1.5 cm in GTD at baseline must have regressed to <1 cm GTD or reduced by 75% in sum of products of greatest diameters, no new lesions, spleen & other previously enlarged organs must have regressed in size & must not be palpable) was required. CRi defined as CR except ANC <1000/μL &/or platelets <100,000/μL.
Time Frame
At the end of treatment (within approximately 6 months from randomization)
Title
Rate of veno-occlusive disease (VOD)
Description
Defined as the percentage of participants with VOD. VOD was defined as one of the following (a) the occurrence of bilirubin >=2mg/dL with 2 or more of the following: painful hepatomegaly, weight gain >5%, or ascites, or (b) histologically proven VOD, or (c) 2 or more of the following with hemodynamic and /or ultrasound evidence of VOD: bilirubin >=2mg/dL, painful hepatomegaly, weight gain >5%, or ascites.
Time Frame
2 years from randomization
Secondary Outcome Measure Information:
Title
Frequency of adverse events
Description
Adverse events to be reported during treatment and for at least 9 weeks after last dose. VOD reported for up to 2 years from randomization.
Time Frame
At least 9 weeks after last dose
Title
Minimal residual disease (MRD) negativity
Description
MRD analysis performed at least once in participants with prior assessment of CR or CRi. Bone marrow aspirates, collected at screening and during the study to be sent to the central laboratory and analyzed using multiparametric flow cytometry. A peripheral blood sample to be provided if a participant had an inadequate bone marrow aspirate at screening. MRD negativity considered to be achieved if the lowest value of MRD from the first date of CR/CRi to EoT was <1 × 10^-4 lasts/nucleated cells.
Time Frame
Up to approximately 4 weeks (EoT) from last dose of study drug
Title
Duration of remission (DoR) for Participants Who Achieved CR/CRi
Description
DoR defined as time from date of first response in responders (CR/CRi) to date of progression or death
Time Frame
2 years from randomization
Title
Progression free survival (PFS)
Description
PFS defined as time from date of randomization to earliest date of the death or progressive disease
Time Frame
2 years from randomization
Title
Overall survival (OS)
Description
OS defined as the time from randomization to date of death due to any cause.
Time Frame
2 years from randomization
Title
Rate of hematopoietic stem cell transplantation (HSCT)
Description
HSCT rate defined as the percentage of participants who underwent HSCT following treatment with inotuzumab ozogamicin
Time Frame
2 years from randomization
Title
Post HSCT relapse
Description
Post HSCT relapse defined as the time from date of HSCT to the date of first relapse post HSCT.
Time Frame
2 years from randomization
Title
Post HSCT mortality
Description
Post HSCT mortality defined as the time from date of HSCT to the date of death due to any cause
Time Frame
2 years from randomization
Title
Post HSCT non relapse mortality
Description
Post HSCT non relapse mortality defined as time from date of HSCT to the date of death due to any cause without prior relapse/progression post HSCT
Time Frame
2 years from randomization
Title
Post HSCT relapse related mortality
Description
Post HSCT relapse related mortality defined as time from date of HSCT to the date of death due to any cause with prior relapse/progression post HSCT.
Time Frame
2 years from randomization
Title
Pharmacokinetics, Cmax
Description
Maximum observed drug concentration (end of the infusion)
Time Frame
Pharmacokinetic sample collections during study drug cycles (each cycle is up to 28 days): Cycle 1 days 1, 4, 8, and 15, Cycle 2 days 1 and 8, Cycle 3 days 1 and 8, and Cycle 4 days 1 and 8.
Title
Percentage of patients with positive anti-drug antibody response
Description
Testing for anti-drug antibodies, including neutralizing antibodies
Time Frame
Sample collections: prior to first dose of study drug and approximately 4 weeks after the last dose of study drug
Title
Percentage of patients with laboratory abnormalities (NCI CTCAE grade)
Description
Magnesium, Calcium, Creatinine, Albumin, Alanine aminotransferase, Aspartate aminotransferase, Glucose, Phosphorus, Total Bilirubin, Blood urea nitrogen or urea, Uric acid or urate, Alkaline phosphatase, Lactate dehydrogenase, Gamma glutamyl transpeptidase, Total protein, Amylase and/or Lipase, Platelet Count, White Blood Cell Count (differential), hemoglobin, INR or prothrombin time, Activated partial thromboplastin time.
Time Frame
At least 9 weeks after last dose
Title
Pharmacokinetics, Ctrough
Description
Drug concentration immediately prior to the next dose administration
Time Frame
Pharmacokinetic sample collections during study drug cycles (each cycle is up to 28 days): Days 8 and 15 of Cycle 1 and day 8 of cycles 2-4)
Title
Pharmacokinetics, Clearance
Description
Volume of plasma cleared of drug per unit of time, calculated using non-linear mixed effects modeling
Time Frame
Pharmacokinetic sample collections during study drug cycles (each cycle is up to 28 days): Cycle 1 days 1, 4, 8, and 15, Cycle 2 days 1 and 8, Cycle 3 days 1 and 8, and Cycle 4 days 1 and 8.
Title
Pharmacokinetics, Area under the curve (AUC)
Description
Calculated using non-linear mixed effects modeling
Time Frame
Pharmacokinetic sample collections during study drug cycles (each cycle is up to 28 days): Cycle 1 days 1, 4, 8, and 15, Cycle 2 days 1 and 8, Cycle 3 days 1 and 8, and Cycle 4 days 1 and 8.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Relapsed or refractory precursor CD22 positive B cell ALL with M2 or M3 marrow (≥5% blasts) and who are eligible for HSCT; Have 1 or more of the following risk factors for developing VOD: Due to receive Salvage 2 or greater; Prior HSCT; Age ≥55 years. Ongoing or prior hepatic disease which may include a prior history of hepatitis or drug induced liver injury, as well as hepatic steatosis, nonalcoholic steatohepatitis, baseline elevations of bilirubin > upper limit of normal (ULN) and ≤1.5 x ULN. Ph+ ALL patients must have failed treatment with at least 1 second or third generation tyrosine kinase inhibitor and standard multi agent induction chemotherapy; Patients in Salvage 1 with late relapse should be deemed poor candidates for reinduction with initial therapy; Patients with lymphoblastic lymphoma and bone marrow involvement 5% lymphoblasts by morphologic assessment; Age 18 years to 75 years; Eastern Cooperative Oncology Group (ECOG) performance status 0 2; Adequate liver function, including total serum bilirubin ≤1.5 x ULN unless the patient has documented Gilbert syndrome, and aspartate and alanine aminotransferase (AST and ALT) ≤2.5 x ULN; Serum creatinine ≤1.5 x ULN or any serum creatinine level associated with a measured or calculated creatinine clearance of >=40 mL/min; Male and female patients of childbearing potential and at risk for pregnancy must agree to use a highly effective method of contraception throughout the study and for a minimum of 8 months (females) and 5 months (males) after the last dose of assigned treatment. A patient is of childbearing potential if, in the opinion of the Investigator, he/she is biologically capable of having children and is sexually active. Female subjects of nonchildbearing potential must meet at least 1 of the following criteria: Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle stimulating hormone (FSH) level confirming the postmenopausal state; Have undergone a documented hysterectomy and/or bilateral oophorectomy; Have medically confirmed ovarian failure. All other female subjects (including female subjects with tubal ligations) are considered to be of childbearing potential. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study; patients with mental capacity which requires the presence of a legally authorized representative will be excluded from the study; Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Exclusion Criteria: Isolated extramedullary relapse (ie, testicular or central nervous system); Burkitt's or mixed phenotype acute leukemia based on the WHO 2008 criteria; Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS directed local treatment for active disease within the prior 28 days, symptomatic CNS leukemia (ie, cranial nerve palsies or other significant neurologic dysfunction) within 28 days. Prophylactic intrathecal medication is not a reason for exclusion; Prior chemotherapy within 2 weeks before randomization with the following exceptions: To reduce the circulating lymphoblast count or palliation: ie, steroids, hydroxyurea or vincristine; For ALL maintenance: mercaptopurine, methotrexate, vincristine, thioguanine, and/or tyrosine kinase inhibitors. Patients must have recovered from acute non hematologic toxicity (to Grade 1 or less) of all previous therapy prior to enrollment. Prior monoclonal antibodies within 6 weeks of randomization, with the exception of rituximab which must be discontinued at least 2 weeks prior to randomization; Prior inotuzumab ozogamicin treatment or other anti CD22 immunotherapy within 6 months before randomization; Prior allogeneic hematopoietic stem cell transplant (HSCT) within 90 days before randomization. Patients must have completed immunosuppression therapy for treatment of graft versus host disease (GvHD) prior to enrollment. At randomization, patients must not have Grade 2 or higher acute GvHD, or extensive chronic GvHD; Peripheral absolute lymphoblast count >=10,000 /L (treatment with hydroxyurea and/or steroids/vincristine is permitted within 2 weeks of randomization to reduce the white blood cell [WBC] count); Known systemic vasculitides (eg, Wegener's granulomatosis, polyarteritis nodosa, systemic lupus erythematosus), primary or secondary immunodeficiency (such as human immunodeficiency virus [HIV] infection or severe inflammatory disease); Active hepatitis B infection as evidenced by hepatitis B surface antigen, active hepatitis C infection (must be anti-hepatitis C antibody negative or hepatitis C ribonucleic acid negative), or known seropositivity for HIV. HIV testing may need to be performed in accordance with local regulations or local practice; Major surgery within 4 weeks before randomization; Unstable or severe uncontrolled medical condition (eg, unstable cardiac function or unstable pulmonary condition); Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ of the cervix, or localized prostate cancer that has been definitely treated with radiation or surgery. Patients with previous malignancies are eligible provided that they have been disease free for >=2 years; Patients with active heart disease or the presence of New York Heart Association (NYHA) stage III or IV congestive heart failure; QTcF >470 msec (based on the average of 3 consecutive electrocardiogram [ECGs]); Myocardial infarction within 6 months before randomization; History of clinically significant ventricular arrhythmia, or unexplained syncope not believed to be vasovagal in nature, or chronic bradycardic states such as sinoatrial block or higher degrees of atrioventricular (AV) block unless a permanent pacemaker has been implanted; Uncontrolled electrolyte disorders that can compound the effects of a QTc prolonging drug (eg, hypokalemia, hypocalcemia, hypomagnesemia); Prior confirmed or ongoing hepatic veno occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS), or other serious or current ongoing liver disease such as cirrhosis or nodular regenerative hyperplasia; Administration of live vaccine within 6 weeks before randomization; Evidence of uncontrolled current serious active infection (including sepsis, bacteremia, fungemia) or patients with a recent history (within 4 months) of deep tissue infections such as fascitis or osteomyelitis; Patients who have had a severe allergic reaction or anaphylactic reaction to any humanized monoclonal antibodies; Pregnant female subjects; breastfeeding female subjects; fertile male subjects and female subjects of childbearing potential who are unwilling or unable to use highly effective contraception as outlined in this protocol for the duration of the study and for a minimum of 8 months (females) and 5 months (males) after the last dose of investigational product; Investigative site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study; Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry and/or during study participation (up through the end of treatment visit); Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Keck Hospital of USC
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
LAC+USC Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
USC/Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Maryland- Greenebaum Comprehensive Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-1028
Country
United States
Facility Name
University of Washington Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
Facility Name
Debreceni Egyetem Klinikai Központ, Orvosi Kepalkotó Klinika, Radiológia
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Facility Name
Debreceni Egyetem Klinikai Központ, Pathológiai lntézet
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Facility Name
Szabolcs-Szatmar Bereg Megyei Korhazak es Egyetemi Oktatokorhaz, Josa Andras Korhaz, Hematologia
City
Nyiregyhaza
ZIP/Postal Code
4400
Country
Hungary
Facility Name
Artemis hospital
City
Gurugram
State/Province
Haryana
ZIP/Postal Code
122001
Country
India
Facility Name
Sahyadri Clinical Research and Development Centre
City
Pune
State/Province
Maharashtra
ZIP/Postal Code
411004
Country
India
Facility Name
Sahyadri Super Speciality Hospital
City
Pune
State/Province
Maharashtra
ZIP/Postal Code
411004
Country
India
Facility Name
Sahyadri Super Speciality Hospital Nagar Road
City
Pune
State/Province
Maharashtra
ZIP/Postal Code
411006
Country
India
Facility Name
Sahyadri Super Speciality Hospital
City
Pune
State/Province
Maharashtra
ZIP/Postal Code
411006
Country
India
Facility Name
Christian Medical College
City
Vellore
State/Province
Tamil NADU
ZIP/Postal Code
632004
Country
India
Facility Name
Christian Medical College Vellore- Ranipet Campus
City
Ranipet - 632517, Tamil Nadu, India
ZIP/Postal Code
632517
Country
India
Facility Name
Klinika Hematologii i Transplantologii, Uniwersyteckie Centrum Kliniczne
City
Gdansk
ZIP/Postal Code
80-214
Country
Poland
Facility Name
Instytut Hematologii i Transfuzjologii
City
Warsaw
ZIP/Postal Code
02-776
Country
Poland
Facility Name
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza - Radeckiego we Wroclawiu
City
Wroclaw
ZIP/Postal Code
50-367
Country
Poland
Facility Name
Apteka Centralna
City
Wroclaw
ZIP/Postal Code
50-556
Country
Poland
Facility Name
National University Hospital
City
Singapore
ZIP/Postal Code
119074
Country
Singapore
Facility Name
Raffles Hospital
City
Singapore
ZIP/Postal Code
188770
Country
Singapore
Facility Name
Raffles Radiology
City
Singapore
ZIP/Postal Code
188770
Country
Singapore
Facility Name
Hospital Universitario Central de Asturias
City
Oviedo
State/Province
Asturias
ZIP/Postal Code
33011
Country
Spain
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital General Universitario Gregorio Maranon
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Hospital Universitario Ramon y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hospital General - Semisótano
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocio
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Hospital Clinico Universitario de Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
Hospital Universitari i Politecnic La Fe
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Changhua Christian Hospital
City
Changhua
ZIP/Postal Code
500
Country
Taiwan
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Anadolu Health Center Hospital
City
Gebze
State/Province
Istanbul
ZIP/Postal Code
41400
Country
Turkey
Facility Name
Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital Clinical Research Center
City
Ankara
ZIP/Postal Code
06200
Country
Turkey
Facility Name
Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital Hematology Department
City
Ankara
ZIP/Postal Code
06200
Country
Turkey
Facility Name
Ankara University Faculty of Medicine Cebeci Hospital Hematology Department
City
Ankara
ZIP/Postal Code
06590
Country
Turkey
Facility Name
Private Medstar Antalya Hosp. Hematology and Stem Cell Transplantation Center
City
Antalya
ZIP/Postal Code
07050
Country
Turkey
Facility Name
Marmara University Pendik Training and Research Hospital Hematology Unit
City
Istanbul
ZIP/Postal Code
34899
Country
Turkey
Facility Name
Ege University Medical Faculty
City
Izmir
ZIP/Postal Code
35100
Country
Turkey
Facility Name
Dokuz Eylul University Medical Faculty
City
Izmir
ZIP/Postal Code
35340
Country
Turkey
Facility Name
Medicalpark Izmir Hospital
City
Izmir
ZIP/Postal Code
35575
Country
Turkey
Facility Name
Erciyes Universitesi Tip Fakultesi Hastaneleri
City
Kayseri
ZIP/Postal Code
38039
Country
Turkey
Facility Name
Ondokuz Mayis University Faculty Of Medicine Hospital
City
Samsun
ZIP/Postal Code
55200
Country
Turkey

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Citations:
PubMed Identifier
35622074
Citation
Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704.
Results Reference
derived
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=B1931030
Description
To obtain contact information for a study center near you, click here.

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A Study Of Two Inotuzumab Ozogamicin Doses in Relapsed/ Refractory Acute Lymphoblastic Leukemia Transplant Eligible Patients

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