Acute Myeloid Leukemia Clinical Trial

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

Summary

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.

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Full Description

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.

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Eligibility Criteria

Inclusion Criteria:

Age: >3 months to <18 years of age.

Diagnosis: Patients must have documented relapsed/refractory ALL, AML, or acute leukemia of ambiguous lineage and meet the following criteria:

Patients must have at least received an appropriate induction therapy regimen. Patients with persistent leukemia after induction therapy, or with recurrence of leukemia at any time during the course of treatment (including allogeneic HSCT) are eligible;
Patients must have > 10% leukemic blasts in the bone marrow;
Patients must have rearrangement involving the MLL gene, including reciprocal chromosomal translocations involving 11q23 by FISH, cytogenetic analysis, polymerase chain reaction (PCR) or next-generation sequencing (NGS) OR partial tandem duplication (PTD) of MLL by PCR or NGS.
Therapeutic Options: Patients must be ineligible or inappropriate for other treatment regimens known to have curative potential.
Performance Level: Karnofsky > 50% for pts > 12 years; Lansky > 50% for pts < 12 years of age.

Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

Myelosuppressive Chemotherapy:

14 days must have elapsed since the completion of cytotoxic therapy
Patients may receive hydroxyurea, low-dose cytarabine and/or glucocorticoids to control peripheral blood leukemic cell counts at study entry
At least 7 days since the completion of therapy with hematopoietic growth factors
At least 7 days since the completion of therapy with a biologic agent
At least 21 days since receipt of chimeric antigen receptor therapy or other modified T cell therapy
At least 60 days from prior total body irradiation (TBI)
At least 60 days must have elapsed from hematopoietic stem cell transplantation (HSCT)

Renal and Hepatic Function: Patient must have adequate renal and hepatic functions as indicated by the following laboratory values:

Patient must have a calculated creatinine clearance or radioisotope GFR > 60mL/min/1.73m2 or a normal serum creatinine based on age/gender
Total bilirubin < 1.5 x ULN for age or normal conjugated bilirubin
ALT and AST < 3 x ULN (unless attributed to leukemic involvement)
Cardiac Function: Patient must have a shortening fraction (SF) of > 27% or an ejection fraction (EF) of > 50% by echocardiogram or MUGA scan.

Exclusion Criteria:

Patients with CNS 3 disease or symptomatic CNS disease
Clinically active heart disease including prolonged QTc or prolonged PR interval, or history of arrhythmias
On immunosuppressive or other anti-leukemic therapy, excluding patients receiving glucocorticoids for management of circulating blast count or patients on a stable dose (<20mg/m2/day prednisone or equivalent) of systemic or topical glucocorticoid therapy with ≤ Grade 1 GvHD or tapering dose of calcineurin inhibitor
Patients with known bleeding diathesis or prothrombin time (PT) or aPTT >1.5 x ULN or fibrinogen <0.5 x LLN
Receiving prophylactic use of hematopoietic colony stimulating factors
Known history of infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCV positive)
Being actively treated for another concurrent malignancy
Pregnant or nursing females;
Male patients not willing to use a condom
Uncontrolled intercurrent illness including, but not limited to uncontrolled infection, significant graft-versus-host-disease (GvHD) (Grade 2-4), or psychiatric illness/social situations that would limit compliance with study requirements
Patients who are concurrently receiving strong inducers/inhibitors of CYP3A
Patients with known history of Trisomy 21 (Down Syndrome), history of congenital immunodeficiency or inherited marrow failure disorder.
Patients with known bleeding diathesis, or PT (Prothrombin time) or aPTT (activated partial thromboplastin time) > 1.5x ULN or <0.5x LLN.

Study is for people with:

Acute Myeloid Leukemia

Phase:

Phase 1

Estimated Enrollment:

18

Study ID:

NCT02141828

Recruitment Status:

Completed

Sponsor:

Epizyme, Inc.

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There are 8 Locations for this study

See Locations Near You

Childrens Hospital Los Angeles
Los Angeles California, 90027, United States
University of California San Francisco Medical Center-Parnassus
San Francisco California, 94143, United States
Children's Hospital Colorado
Aurora Colorado, 80045, United States
Emory Children's Healthcare of Atlanta
Atlanta Georgia, 30322, United States
Johns Hopkins University
Baltimore Maryland, 21287, United States
Dana Farber Cancer Institute
Boston Massachusetts, 02215, United States
Memorial Sloan Kettering Cancer Center
New York New York, 10065, United States
Cincinnati Children's Hospital Medical Center
Cincinnati Ohio, 45229, United States
The Hospital for Sick Kids
Toronto Ontario, , Canada

How clear is this clinincal trial information?

Study is for people with:

Acute Myeloid Leukemia

Phase:

Phase 1

Estimated Enrollment:

18

Study ID:

NCT02141828

Recruitment Status:

Completed

Sponsor:


Epizyme, Inc.

How clear is this clinincal trial information?

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