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EPZ-5676 Dose escalation and expansion cohorts

28-day continuous IV infusion of each 28-day cycle, given until disease progression or unacceptable toxicity develops.

EPZ-5676

Neal Shukla, MD

Lia Gore, MD

Pat Brown, MD

Lewis Silverman, MD

Maureen O'Brien, MD

Jim A Whitlock, MD

Cynthia Wetmore, MD PhD

Mignon Loh, MD

Paul Gaynon, MD

Todd Cooper, MD

A subset of patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) harbor rearrangements of the MLL gene, which are detected either by cytogenetic or fluorescent in situ hybridization evaluation at the time of diagnosis. A protein called DOT1L plays an important role in the malignant process in these leukemias. EPZ-5676 is a molecule that blocks the activity of DOT1L, and is therefore being evaluated in the treatment of patients with MLL-rearranged leukemias.

This is a Phase 1b study of EPZ-5676 in pediatric patients. The study will have two phases. The first phase will assess escalating doses of EPZ-5676 in order to determine the maximally tolerated dose (MTD) or recommended phase 2 dose (RP2D) of EPZ-5676 as a 28-day continuous IV infusion. Once the MTD and/or RP2D is established, a second phase of the study will further evaluate the safety of EPZ-5676 and assess the anti-leukemia activity.

A Phase 1 Dose Escalation and Expanded Cohort Study of EPZ-5676 in the Treatment of Pediatric Patients With Relapsed/Refractory Leukemias Bearing a Rearrangement of the MLL Gene

Somatic mutations to include mRNA and proteins or markers of biological pathways as potential predictors of response to EPZ-5676 treatment

To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of EPZ-5676 as determined by incidence of protocol-specified dose-limiting adverse events.

Safety and tolerability will be assessed by the incidence of adverse events in patients treated with EPZ-5676 and the evaluation of adverse events, vital signs, physical examination, 12-lead ECG, and laboratory assessments.

The pharmacokinetic (PK) profile will include the analysis of Cmax, AUC and steady state concentration of EPZ-5676.

The pharmacodynamic (PD) profile will assess the effects of EPZ-5676 in peripheral blood mononuclear (PBMC) and bone marrow cells.

Anti-tumor activity will be assessed by objective response (OR) in pediatric patients

Celgene Corporation

Epizyme, Inc.

Spots Global Cancer Trial Database for ambiguous lineage