Description:
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).
Title
- Brief 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
- 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
Clinical Trial IDs
- ORG STUDY ID:
EPZ-5676-12-001
- NCT ID:
NCT01684150
Conditions
- Acute Myeloid Leukemia
- Acute Lymphoblastic Leukemia
- Myelodysplastic Syndrome
- Myeloproliferative Disorders
Interventions
Drug | Synonyms | Arms |
---|
EPZ-5676 | | EPZ-5676 Extension cohort |
Purpose
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).
Detailed Description
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).
Trial Arms
Name | Type | Description | Interventions |
---|
EPZ-5676 Extension cohort | Experimental | | |
Eligibility 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.
Maximum Eligible Age: | 90 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | 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 |
Safety Issue: | |
Description: | 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). |
Secondary Outcome Measures
Measure: | Pharmacokinetic profile of EPZ-5676 |
Time Frame: | up to 24 months |
Safety Issue: | |
Description: | analysis of Cmax, AUC and steady state concentration |
Measure: | The incidence of adverse events in patients treated with EPZ-5676 |
Time Frame: | up to 24 months |
Safety Issue: | |
Description: | Evaluation of adverse events, vital signs, physical examination, 12-lead ECG, and laboratory assessments |
Measure: | Anti-leukemic activity of EPZ-5676 in patients with acute leukemia harboring a MLL-rearrangement |
Time Frame: | up to 24 months |
Safety Issue: | |
Description: | Evaluation of response by standard criteria for AML or ALL |
Measure: | Effects of EPZ-5676 on histone H3K79 methylation in peripheral blood mononuclear cells (PBMC). |
Time Frame: | up to 24 months |
Safety Issue: | |
Description: | |
Measure: | Effects of EPZ-5676 on histone H3K79 methylation in leukemia cells |
Time Frame: | up to 24 months |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Epizyme, Inc. |
Trial Keywords
- Leukemia
- Advanced hematologic malignancies
- Epizyme
- Phase 1
- Mixed Lineage Leukemia (MLL)
Last Updated
August 4, 2016