Details
Description
Inclusion Criteria
Exclusion Criteria
Details
Title A Phase 3 randomized trial of Blinatumomab for newly diagnosed BCR-ABL negative B lineage acute lymphoblastic leukemia in adults
IRB ECOG 1910
CC 14-121
Hospital Florida Weston, Main Campus
Phase Phase 3
Disease Leukemia - Acute Lymphoblastic (ALL)
Drug Blinotumomab
Description
Primary Objectives- To compare the overall survival (OS) of blinatumomab in conjunction with chemotherapy to chemotherapy alone in patients with BCR-ABL-negative B cell precursor ALL who are MRD positive after induction and intensification chemotherapy, based on multiparameter flow cytometric (MFC) assessment of residual blasts.
- If superiority of blinatumomab in the MRD positive group is shown, to compare the OS of blinatumomab in conjunction with chemotherapy to chemotherapy alone in patients with BCR-ABL-negative B cell precursor ALL who are MRD negative after induction and intensification chemotherapy, based on MFC assessment of residual blasts.
- If superiority of blinatumomab in the MRD positive group is not shown, to compare the OS of blinatumomab in conjunction with chemotherapy to chemotherapy alone in the overall population of patients with BCR-ABL-negative B cell precursor ALL.
- To determine if blinatumomab can convert patients who are MRD positive by MFC assessment of residual blasts after induction and intensification chemotherapy to MRD negativity.
- To assess the toxicities of blinatumomab in this patient population
- To assess the toxicities of the modified E2993 chemotherapy regimen in this patient population.
- To describe the outcome of patients who proceed to allogeneic blood or marrow transplant after treatment with or without blinatumomab.
- To determine differences in MRD kinetics among patients with the BCR/ABL1-like B-lineage ALL, and assess the efficacy of blinatumomab in each molecular subgroup.
- To evaluate the incidence of anti-blinatumomab antibody formation.
Inclusion Criteria
- Age ≥ 30 years and ≤ 70 years. New diagnosis of B lineage ALL must be made upon bone marrow or peripheral blood immunophenotyping. Cases with myeloid antigen expression, but unequivocal lymphoid immunophenotype, are eligible.
- Mature B ALL (Burkitt's-like leukemia) is excluded from enrollment in this trial.
- Negativity for the Philadelphia chromosome must be established by conventional cytogenetics, FISH and/or PCR. Patients who are negative for the Philadelphia chromosome by conventional cytogenetics must have FISH or PCR performed for BCR/ABL to exclude occult translocations.
- Cytogenetic analysis must be performed from diagnostic bone marrow (preferred) or if adequate number of circulating blasts from peripheral blood. FISH testing for common B-lineage ALL abnormalities including t(9;22) (BCR/ABL1), t(12;21) (ETV6/RUNX1), t(1;19) (PBX1/TCF3), +4,+10,+17, (Cen4/Cen10/Cen17), t(11q23;var), (MLL), del(9p) (CDKN2A/Cen9), and t(14;var) (IGH is encouraged.
- Patient must not have a concurrent active malignancy for which they are receiving treatment.
- Have lab values obtained ≤ 1 week prior to registration. Serum direct bilirubin < 2 mg/dl and serum creatinine < 2 mg/dl. NOTE: The above stipulation for normal hepatic function does not apply if liver dysfunction is due to leukemia infiltration.
- Patient should be HLA typed (A, B, C, DR and DQ) during induction therapy phase or a written explanation for not undergoing HLA typing on the flow sheet.
- Patient must not have intercurrent organ damage or medical problems that will jeopardize the outcome of therapy (i.e., psychiatric disorder, drug abuse, pregnancy).
- Patients with known HIV infections are not eligible
- Patient must not have an antecedent hematologic disorder.
- Patient must have no history of recent myocardial infarction (within three months), uncontrolled congestive heart failure, or uncontrolled cardiac arrhythmia.
- Patient must not have a history or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis, or other significant CNS abnormalities.
- Patient must have a normal cardiac ejection fraction by pretreatment MUGA or echocardiogram within 4 weeks prior to registration (resting ejection fraction ≥ 40% or ≥ 5% increase with exercise), shortening fraction by echocardiogram ≥ 24%, or to within the normal range of values for the institution.
- Patient must not have an active uncontrolled infection.
- Women must not be pregnant or breast-feeding due to administration of teratogenic chemotherapy and must not become pregnant or breastfeed during protocol therapy and for at least 3 months after protocol therapy. Woman of childbrearing potential must abstain from sexual activity or be willing to use 2 highly effective forms of contraception throughout protocol therapy and for at least an additional 3 months after the last dose of protocol-specified therapy. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy. A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
- Men who have a female partner of childbearing potential must be willing to use 2 highly effective forms of contraception throughout protocol therapy and for at least an additional 3 months after the last dose of protocol-specified therapy. Men who have a pregnant partner must be willing to use a condom during sexual activity throughout protocol therapy and for 3 months after the last dose of protocol-specified therapy.
- ECOG performance score 0-3.
- Patient must have given written informed consent.