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

NCT01684150 | Completed Phase 1

• 2 other identifiers: EPZ-5676-12-0012013-002355-15
• Study Type: interventional
• Target: 51
• Locations: 3 countries
• Sites: 8

Brief 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).

Conditions

Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndrome; Myeloproliferative Disorders

Keywords

Leukemia; Advanced hematologic malignancies; Epizyme; Phase 1; Mixed Lineage Leukemia (MLL)

Outcome Measures

Primary Outcomes (1)

• 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.

  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).

  up to 12 months

Secondary Outcomes (5)

• Pharmacokinetic profile of EPZ-5676

  up to 24 months

• The incidence of adverse events in patients treated with EPZ-5676

  up to 24 months

• Anti-leukemic activity of EPZ-5676 in patients with acute leukemia harboring a MLL-rearrangement

  up to 24 months

• Effects of EPZ-5676 on histone H3K79 methylation in peripheral blood mononuclear cells (PBMC).

  up to 24 months

• Effects of EPZ-5676 on histone H3K79 methylation in leukemia cells

  up to 24 months

Study Arms (1)

EPZ-5676 Extension cohort

EXPERIMENTAL

Drug: EPZ-5676

Interventions

EPZ-5676 DRUG

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.

EPZ-5676 Extension cohort

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients aged ≥ 18 years.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• 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

You may not qualify if:

• Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements.
• Active heart disease
• Receiving any other standard treatment for their hematologic malignancy.
• Receiving strong CYP3A4 inhibitors/ inducers.
• Known history of cerebrovascular accident in the past 6 months.
• Known bleeding diathesis.
• Known, active (symptomatic) involvement of the central nervous system by leukemia.
• On immunosuppressive therapy.
• Known active infection.
• Pregnant or nursing females.

Sponsors & Collaborators

• Epizyme, Inc.: lead
• Celgene: collaborator

Study Sites (8)

Mayo Clinic Scottsdale-Phoenix

Scottsdale, Arizona, 85259, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

UT MD Anderson Cancer

Houston, Texas, 77030, United States

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Erasmus University Medical Center

Rotterdam, Netherlands

Location

Related Publications (1)

• Stein EM, Garcia-Manero G, Rizzieri DA, Tibes R, Berdeja JG, Savona MR, Jongen-Lavrenic M, Altman JK, Thomson B, Blakemore SJ, Daigle SR, Waters NJ, Suttle AB, Clawson A, Pollock R, Krivtsov A, Armstrong SA, DiMartino J, Hedrick E, Lowenberg B, Tallman MS. The DOT1L inhibitor pinometostat reduces H3K79 methylation and has modest clinical activity in adult acute leukemia. Blood. 2018 Jun 14;131(24):2661-2669. doi: 10.1182/blood-2017-12-818948. Epub 2018 May 3.

  PMID: 29724899 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Myeloproliferative Disorders; Leukemia

Interventions

EPZ-5676

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2012
• First Posted: September 12, 2012
• Study Start: September 1, 2012
• Primary Completion: November 1, 2015
• Study Completion: February 1, 2016
• Last Updated: March 26, 2024

Record last verified: 2024-03

Locations

NL (1); US (6); DE (1)