A Study of the Drug IMGN632 in Children With Leukemia That Has Come Back After Treatment or is Difficult to Treat

PRIMARY OBJECTIVES:

I. To determine the recommended phase 2 dose (RP2D) of anti-CD123 ADC IMGN632 (IMGN632) monotherapy in pediatric patients with second or greater relapse of CD123 positive leukemia or CD123 positive leukemia refractory to relapse therapy. (Cohort 1 \[Monotherapy Phase 1\]) II. To assess the flow-based overall response rate (complete remission \[CR\]/CR with incomplete blood count recovery \[CRi\]/CR with partial recovery of platelet count \[CRp\]) in patients with acute myeloid leukemia (AML) treated with IMGN632. (Cohort 1 \[Monotherapy Phase 1\]) III. To determine the safety, feasibility, and RP2D of IMGN632 in combination with liposome-encapsulated daunorubicin-cytarabine (DAUNOrubicin and cytarabine liposome) in pediatric patients with first relapse of CD123 positive AML. (Cohort 2 \[Combination Therapy Dose Finding\]) IV. To compare the minimal residual disease (MRD) negative flow-based overall response rate (CR/CRi/CRp) in pediatric patients with first relapse of CD123 positive AML randomized to two cycles of therapy including DAUNOrubicin and cytarabine liposome followed by fludarabine phosphate (fludarabine)/cytarabine with or without IMGN632. (Cohort 3 \[Randomized Phase 2\])

SECONDARY OBJECTIVE:

I. To characterize the pharmacokinetics of IMGN632 in a pediatric population. (Cohort 1 \[Monotherapy Phase 1\])

EXPLORATORY OBJECTIVES:

I. To describe the anti-leukemic activity (morphologic and flow-based CR/CRp/CRi after up to two cycles, rates of MRD negative response after up to 2 cycles, event free survival \[EFS\] and overall survival \[OS\]) of IMGN632 in patients with multiply relapsed or refractory relapsed pediatric leukemia including AML, B-cell acute lymphoblastic leukemia \[ALL\], T-cell ALL and mixed phenotype acute leukemia (MPAL). (Cohort 1) II. To describe the EFS, OS, cumulative incidence of relapse, and rate of subsequent stem cell transplant for patients with first relapse of AML randomized to treatment with up to two cycles of chemotherapy with or without IMGN632. (Cohort 3) III. To determine if CD123 expression on leukemic blasts (assessed by flow cytometry) correlates with clinical response to IMGN632. (All Cohorts) IV. To determine the cumulative incidence of left ventricular systolic dysfunction (LVSD), defined as an absolute decline in EF by \>= 10% to an ejection fraction (EF) value of \< 50%, or an absolute decline in shortening fraction (SF) by \>= 4% to an SF value of \< 25%, within 1 year of initiation of DAUNOrubicin and cytarabine liposome based therapy for relapsed pediatric AML.