Health Condition 1: C910- Acute lymphoblastic leukemia [ALL]
Conditions
Interventions
Intervention1: Inotuzumab Ozogamicin (Dose Level 2)
: 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 l
Sponsors
Pfizer Inc
Pfizer Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1. Relapsed or refractory precursor CD22-positive B-cell ALL with M2 or M3 marrow (greater than equal to 5% blasts) and who are eligible for HSCT 2. Have 1 or more of the following risk factors for developing VOD a. Due to receive Salvage 2 or greater b. Prior HSCT c. Age greater than equal to 55 years d. 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 greater than upper limit of normal (ULN) and less than equal to 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 greater than equal to 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 less than equal to 1.5 x ULN unless the patient has documented Gilbert syndrome, and aspartate and alanine aminotransferase (AST and ALT) less than equal to 2.5 x ULN. 9. Serum creatinine less than equal to 1.5 x ULN or any serum creatinine level associated with a measured or calculated creatinine clearance of greater than equal to 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: a. 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 b. Have undergone a documented hysterectomy and/or bilateral oophorectomy c. 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
Exclusion criteria: 1. Isolated extramedullary relapse (ie, testicular or central nervous system) 2. Burkittâ??s or mixed phenotype acute leukemia based on the WHO 2008 criteria 3. Active central nervous system leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid, use of CNS directed local treatment for active disease within the prior 28 days, symptomatic CNS leukemia (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 a. To reduce the circulating lymphoblast count or palliation that is steroids, hydroxyurea or vincristine b. For ALL maintenance mercaptopurine, methotrexate, vincristine, thioguanine, and,or tyrosine kinase inhibitors Patients must have recovered from acute non hematologic toxicity (to less than equal to Grade 1) 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 antiCD22 immunotherapy less than equal to 6 months before randomization 7.Prior allogeneic hematopoietic stem cell transplant less than equal to 90 days before randomization. Patients must have completed immunosuppression therapy for treatment of graft versus host disease prior to enrollment. At randomization, patients must not have greater than equal to Grade 2 acute GvHD, or extensive chronic GvHD 8. Peripheral absolute lymphoblast count greater than equal to 10,000 per µL (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 (example Wegenerâ??s granulomatosis, polyarteritis nodosa, systemic lupus erythematosus), primary or secondary immunodeficiency (such as human immunodeficiency virus 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 less than equal to 4 weeks before randomization 12. Unstable or severe uncontrolled medical condition (example 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 greater than equal to 2 years 14. Patients with active heart disease or the presence of New York Heart Association stage III or IV congestive heart failure 15. QTcF greater than 470 msec (based on the average of 3 consecutive electrocardiogram) 16. Myocardial infarction less than equal to 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 sin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Percentage of Participants With Hematologic Remission (Complete Remission [CR]/Complete Remission With Incomplete Hematologic Recovery [CRi]) 2. Rate of veno-occlusive disease (VOD) Timepoint: 1. At the end of treatment (within approximately 6 months from randomization) 2. Two years from randomization | — |
Secondary
| Measure | Time frame |
|---|---|
| Duration of remission (DoR) for Participants Who Achieved CR/CRiTimepoint: 2 years from randomization;Frequency of adverse eventsTimepoint: 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) negativityTimepoint: Up to approximately 4 weeks (EoT) from last dose of study drug;Overall survival (OS)Timepoint: 2 years from randomization;Percentage of patients with laboratory abnormalities (NCI CTCAE grade)Timepoint: At least 9 weeks after last dose;Percentage of patients with positive anti-drug antibody responseTimepoint: Sample collections: prior to first dose of study drug and approximately 4 weeks after the last dose of study drug;Pharmacokinetics, Area under the curve (AUC)Timepoint: 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;Pharmacokinetics, ClearanceTimepoint: 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;Pharmacokinetics, CmaxTimepoint: 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;Pharmacokinetics, CtroughTimepoint: 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);Post HSCT mortalityTimepoint: 2 years from randomization;Post HSCT non relapse mortalityTimepoint: 2 years from randomization;Post HSCT relapseTimepoint: 2 years from randomization;Post HSCT relapse related mortalityTimepoint: 2 years from randomization;Progression free survival (PFS)Timepoint: 2 years from randomization;Rate of hematopoietic stem cell transplantation | — |
Countries
Australia, Belgium, Hungary, India, Poland, Singapore, Spain, Taiwan, Turkey, United States of America
Contacts
Public ContactDr Seema Pai
Pfizer Limited
Outcome results
None listed