A Phase III Study of Risk Directed Therapy for Infants with Acute Lymphoblastic Leukemia (ALL): Randomization of Highest Risk Infants to Intensive Chemotherapy +/- FLT3 Inhibition (CEP-701, Lestaurtinib; IND#76431; NSC#617807)
This phase III trial is studying giving lestaurtinib together with combination chemotherapy to see how well it works compared to combination chemotherapy alone in treating infants with newly diagnosed acute lymphoblastic leukemia.
Ages up to 1 Year Newly diagnosed acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia T-cell ALL allowed Bilineage or biphenotypic acute leukemia allowed provided the morphology and immunophenotype are predominately lymphoid Must be less than 366 days of age at diagnosis; neonates in the first month of life must be greater than 36 weeks gestational age at diagnosis Must be enrolled on protocol COG-AALL03B1 prior to enrollment on this protocol Previously untreated except for the following: Steroid treatment within the past 48 hours allowed, provided that a physical examination and CBC with differential were performed immediately prior to beginning steroids Intrathecal (IT) chemotherapy (per protocol) is allowed for patient convenience at the time of the diagnostic bone marrow or venous line placement to avoid second lumbar puncture No B-cell ALL or acute myelogenous leukemia No Down syndrome
All patients receive induction therapy (weeks 1-3) comprising vincristine IV on days 1, 8, and 15; daunorubicin hydrochloride IV over 30 minutes on days 1 and 2; cyclophosphamide IV over 30 minutes every 12 hours on days 3 and 4; pegaspargase or asparaginase intramuscularly (IM) on day 4; oral prednisone or methylprednisolone IV three times daily on days 1-21; triple intrathecal (IT) chemotherapy comprising methotrexate, cytarabine, and hydrocortisone on days 1, 8, and 15; and filgrastim IV or subcutaneously (SC) beginning on day 5 and continuing until blood counts recover. Standard risk patients are nonrandomly assigned to receive a less intensive chemotherapy regimen without lestaurtinib (post-induction therapy A). A safety/activity phase is conducted separately for the intermediate risk (IR) and high risk (HR) patients to identify a safe, tolerable, and biologically active dose of lestaurtinib combined with P9407-based chemotherapy backbone. Once a tolerable/active dose of lestaurtinib has been identified for IR patients, subsequent IR patients are eligible to proceed to an efficacy phase, where they are randomized to P9407- based chemotherapy backbone with or without lestaurtinib. HR patients separately proceed to the randomized efficacy phase if a tolerable/active dose is identified for the HR stratum. IR and HR patients are randomized to 1 of 2 post-induction therapy regimens (post-induction therapy B or C).
05/22/2013 04:02 AM