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

• Status: Completed
• Trial end date: 2016-02-01
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Epizyme, Inc.
• Collaborator: Celgene

Criteria

Inclusion Criteria:

1. Male and female patients aged ≥ 18 years.

2. Patients with relapsed /refractory AML, ALL, or MLL with rearrangement of the MLL gene, including 11q23 or PTD, are eligible for the expanded cohort:

• At least one prior therapy;

• Refractory disease on most recent therapy, or disease recurrence following remission on most recent therapy;

• Received and failed all known effective therapies for their disease;

• Not a candidate for allogeneic stem cell transplantation

• > 10% blasts or biopsy-documented leukemia cutis or myeloid sarcoma.

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

4. Patients must have the following clinical laboratory values:

• Serum creatinine ≤2 mg/dL or creatinine clearance > 60 mL/minute;

• Total bilirubin ≤2.0 times the ULN for the institution, unless considered due to Gilbert's syndrome;

• ALT or AST ≤ twice the upper limit of normal (ULN), unless considered due to organ leukemic involvement;

• Absolute neutrophil count ≥1,000/µL (unless due to documented leukemic involvement of the bone marrow at the time of study entry)

• Platelets ≥100,000/µL (unless due to documented leukemic involvement of the bone marrow at the time of study entry).

• PT or aPTT < 1.5 times the ULN

5. Able and willing to give written informed consent.

6. Life expectancy of at least 3 months

Exclusion Criteria:

1. Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements.

2. Active heart disease

3. Receiving any other standard treatment for their hematologic malignancy.

4. Receiving strong CYP3A4 inhibitors/ inducers.

5. Known history of cerebrovascular accident in the past 6 months.

6. Known bleeding diathesis.

7. Known, active (symptomatic) involvement of the central nervous system by leukemia.

8. On immunosuppressive therapy.

9. Known active infection.

10. Pregnant or nursing females.