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
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.
Currently this study is in the MLL-r restricted/expansion phase and is only enrolling patients with rearrangements involving the MLL gene, including 11q23 or partial tandem duplications (PTD).
|Acute Myeloid Leukemia Acute Lymphoblastic Leukemia Myelodysplastic Syndrome Myeloproliferative Disorders||Drug: EPZ-5676||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (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) and/or recommended phase 2 dose (RP2D) of EPZ-5676 as determined by incidence of protocol-specified dose-limiting adverse events. [ Time Frame: up to 12 months ]The MTD is defined as the dose level below in which >1 patient out of 3 or >2 patients out of 6 experience dose-limiting adverse events (as defined by the protocol).
- Pharmacokinetic profile of EPZ-5676 [ Time Frame: up to 24 months ]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 ]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 ]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 ]
- Effects of EPZ-5676 on histone H3K79 methylation in leukemia cells [ Time Frame: up to 24 months ]
|Study Start Date:||September 2012|
|Study Completion Date:||February 2016|
|Primary Completion Date:||November 2015 (Final data collection date for primary outcome measure)|
|Experimental: EPZ-5676 Extension cohort||
MLL-r and MLL-PTD 28-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 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.
The dose escalation portion has been completed. Currently this study is in the expansion phase and patients with MLL-r and MLL-PTD will receive EPZ-5676 as a 28-day continuous intravenous infusion (CIV).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01684150
|United States, Arizona|
|Mayo Clinic Scottsdale-Phoenix|
|Scottsdale, Arizona, United States, 85259|
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, North Carolina|
|Duke University Health System|
|Durham, North Carolina, United States, 27710|
|United States, Tennessee|
|Sarah Cannon Research Institute|
|Nashville, Tennessee, United States, 37203|
|United States, Texas|
|UT MD Anderson Cancer|
|Houston, Texas, United States, 77030|
|Ulm, Germany, 89081|
|Erasmus University Medical Center|
|Principal Investigator:||Martin S. Tallman, MD||Memorial Sloan Kettering Cancer Center|
|Principal Investigator:||Jesus Berdeja, MD||SCRI Development Innovations, LLC|
|Principal Investigator:||David A Rizzieri, MD||Duke University|
|Principal Investigator:||Guillermo Garcia-Manero, MD||M.D. Anderson Cancer Center|
|Principal Investigator:||Jessica Altman, MD||Northwestern University|
|Principal Investigator:||Raoul Tibes, MD||Mayo Clinic Scottsdale-Phoenix|
|Principal Investigator:||Mojca Jongen-Lavrencic, MD||Erasmus Medical Center|
|Principal Investigator:||Hartmut Döhner, MD||Universitätsklinikum Ulm|