A First-in-Human Phase 1 and Expanded Cohort Study of EPZ-5676 in Advanced Hematologic Malignancies, Including Acute Leukemia With Rearrangement of the MLL Gene
The purpose of this study is to determine the safe dose of EPZ-5676, to evaluate the safety of EPZ-5676 in patients with advanced hematologic malignancies, and to conduct a preliminary assessment of the anti-leukemia activity of EPZ-5676 in patients with acute leukemias bearing rearrangements of the MLL gene.
Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Chronic Myeloid Leukemia
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1, Open-Label, Dose-Escalation & Expanded Cohort, Continuous IV Infusion, Multi-center Study of the Safety, Tolerability,PK & PD of EPZ-5676 in Treatment Relapsed/Refractory Patients With Leukemias Involving Translocation of the MLL Gene at 11q23 or Advanced Hematologic Malignancies|
- The maximum tolerated dose (MTD) of EPZ-5676 as determined by incidence of protocol-specified dose-limiting adverse events [ Time Frame: up to 12 months ] [ Designated as safety issue: Yes ]The MTD is defined as one dose level below the level in which >1 dose-limiting adverse events (as defined by the protocol) are observed.
- Pharmacokinetic profile of EPZ-5676 [ Time Frame: up to 12 months ] [ Designated as safety issue: No ]analysis of Cmax, AUC and steady state concentration
- The incidence of adverse events in patients treated with EPZ-5676 [ Time Frame: up to 24 months ] [ Designated as safety issue: Yes ]Evaluation of adverse events, vital signs, physical examination, 12-lead ECG, and laboratory assessments
- Anti-leukemic activity of EPZ-5676 in patients with acute leukemia harboring a MLL-rearrangement [ Time Frame: up to 24 months ] [ Designated as safety issue: No ]Evaluation of response by standard criteria for AML or ALL
- Effects of EPZ-5676 on histone H3K79 methylation in peripheral blood mononuclear cells (PBMC). [ Time Frame: up to 24 months ] [ Designated as safety issue: No ]
- Effects of EPZ-5676 on histone H3K79 methylation in leukemia cells [ Time Frame: up to 24 months ] [ Designated as safety issue: No ]
|Study Start Date:||September 2012|
|Estimated Study Completion Date:||November 2014|
|Estimated Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
|Experimental: EPZ-5676 Dose-escalation and extension cohorts||
Dose-escalation, 21-day continuous IV infusion of each 28-day cycle. Number of cycles: until disease progression or unacceptable toxicity develops.
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 flourescent 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 first-in-human study of EPZ-5676. The primary purpose of this study is to determine what dose of EPZ-5676, when administered as a 21-day continuous intravenous infusion, can be given safely to patients with hematologic malignancies. 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) of EPZ-5676. Once the MTD is established, a second phase of the study will further evaluate the safety of EPZ-5676 and assess the anti-leukemia activity of EPZ-5676 in MLL-rearranged leukemia.
|Contact: Eric Hedrick, MDemail@example.com|
|United States, New York|
|Memorial Sloan Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Martin S Tallman, MD 212-639-3842 TallmanM@mskcc.org|
|Principal Investigator: Martin S Tallman, MD|
|United States, Tennessee|
|Sarah Cannon Research Institute||Recruiting|
|Nashville, Tennessee, United States, 37203|
|Contact: Michael Savona, MD 615-986-7604 firstname.lastname@example.org|
|Principal Investigator: Michael Savona, MD|
|Principal Investigator:||Martin S. Tallman, MD||Memorial Sloan-Kettering Cancer Center|
|Principal Investigator:||Michael Savona, MD||Sarah Cannon Research Institute|