This phase III trial studies the side effects of inotuzumab ozogamicin and how well it works when given with frontline chemotherapy in treating patients with newly diagnosed B acute lymphoblastic leukemia. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a chemotherapy drug called ozogamicin. Inotuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD22 receptors, and delivers ozogamicin to kill them. Chemotherapy drugs, such as \[intervention\], work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving inotuzumab ozogamicin with chemotherapy may work better in treating young adults with B acute lymphoblastic leukemia.
Newly diagnosed patients with CD-22 positive B-cell acute lymphoblastic leukemia (WHO criteria) are eligible. Patients with Burkitt type ALL are NOT eligible
REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Single-dose intrathecal cytarabine is allowed prior to registration or prior to initiation of systematic therapy for patient convenience; this is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture; systemic chemotherapy must begin within 72 hours of this intrathecal therapy
REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Age >= 18 years and < 40 years
REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Eastern Cooperative Oncology Group (ECOG) performance status 0-2
REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Patients who have BCR-ABL fusion transcript determined by fluorescence in situ hybridization (FISH) or real time-polymerase chain reaction (RT-PCR) or t(9;22)(q34;q11) by cytogenetics are not eligible and should be considered for enrollment on studies that incorporate imatinib during induction; please note: patients must also be assessed for CD20 positivity and other markers; positivity for CD22 and CD20 is defined as baseline expression of the CD22 or CD20 antigen in more than 20% of leukemic cells using local multiparameter flow-cytometric immunophenotyping with the use of CD45 expression as a marker to gate the ALL blast population, according to recommendations from the European LeukemiaNet
REGISTRATION ELIGIBILITY CRITERIA (STEP 1): No prior therapy for ALL except for limited treatment (=< 7 days) with corticosteroids or hydroxyurea and a single dose of intrathecal cytarabine; however, patients who are being treated with chronic steroids for other reasons (for example, to treat asthma, autoimmune disorders, lupus, etc.) are eligible
REGISTRATION ELIGIBILITY CRITERIA (STEP 1): No prior therapy for acute leukemia except emergency therapy (corticosteroids or hydroxyurea) for blast cell crisis, superior vena cava syndrome, or renal failure due to leukemic infiltration of the kidneys; when indicated, leukapheresis or exchange transfusion is recommended to reduce the WBC
REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Not pregnant and not nursing, because this study involves agents that have known genotoxic, mutagenic and teratogenic effects; therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done =< 8 days prior to registration is required
Parallel
Allopurinol
DrugGiven PO
Cytarabine
DrugGiven IT, IV, SC
Daunorubicin Hydrochloride
DrugGiven IV
Vincristine Sulfate
DrugGiven IV
Dexamethasone
DrugGiven PO or IV
Pegylated L-Asparaginase
DrugGiven IV
Methotrexate
DrugGiven IT, IV, PO
Bone Marrow Aspiration and Biopsy
Procedure/SurgeryUndergo bone marrow aspiration and biopsy
Cyclophosphamide
DrugGiven IV
Mercaptopurine
DrugGiven PO
Rituximab
Biological/VaccineGiven IV
Doxorubicin
DrugGiven IV
Thioguanine
DrugGiven PO
Inotuzumab Ozogamicin
Biological/VaccineGiven IV
Laboratory Biomarker Analysis
Other interventionCorrelative studies
Event-free survival (EFS)
The EFS distributions between the two arms will be compared using non-stratified log-rank tests. EFS curves will be constructed using the Kaplan-Meier product limit method, and additional analyses will be done using the Cox proportional hazards model. with diagnostics test on proportional hazard assumptions first. The corresponding hazard ratio, 2- and 3-year EFS estimates will be assessed, and EFS medians along with their 95% confidence intervals for the two treatment arms.
Disease-free survival (DFS)
Overall Survival (OS)
Will be evaluated using Kaplan-Meier as well as Cox regression models.
Proportion of patients who achieve CR or any response to induction therapy
Will be summarized as the proportion of patients who achieve any type of response to induction therapy divided by the number of all evaluable patients registered to this trial and who received at least one dose of induction therapy. Corresponding 95% binomial confidence intervals will also be calculated.
Overall induction response rates
Will be summarized as the proportion of patients who achieve any type of response to induction therapy divided by the number of all evaluable patients registered to this trial and who received at least one dose of induction therapy. Corresponding 95% binomial confidence intervals will also be calculated.
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Alliance for Clinical Trials in Oncology
Lead sponsor
National Cancer Institute (NCI)
Collaborator
