NCT02141828

Brief 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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
18

participants targeted

Target at P25-P50 for phase_1 leukemia

Timeline
Completed

Started May 2014

Shorter than P25 for phase_1 leukemia

Geographic Reach
2 countries

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2014

Completed
10 days until next milestone

First Submitted

Initial submission to the registry

May 11, 2014

Completed
9 days until next milestone

First Posted

Study publicly available on registry

May 20, 2014

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2016

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2016

Completed
Last Updated

June 18, 2023

Status Verified

May 1, 2020

Enrollment Period

2 years

First QC Date

May 11, 2014

Last Update Submit

June 15, 2023

Conditions

LeukemiaAcute Myeloid LeukemiaAcute Lymphocytic LeukemiaAcute Leukemias

Keywords

LeukemiaAdvanced hematologic malignanciesEpizymePhase 1bMLL gene11q23Ambiguous lineageALLAMLAcute leukemiasMLL-r

Outcome Measures

Primary Outcomes (2)

  • Determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of EPZ-5676.

    To determine 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.

    12 months

  • To assess the safety and tolerability of EPZ-5676 administered as a continuous intravenous (CIV) infusion

    Safety and tolerability will be assessed by the incidence of adverse events in patients treated with EPZ-5676 and the evaluation of adverse events, vital signs, physical examination, 12-lead ECG, and laboratory assessments.

    22 months

Secondary Outcomes (2)

  • Determine the pharmacokinetic (PK) and pharmacodynamic (PD) profile of EPZ-5676

    18 months

  • Evaluate early evidence of anti-tumor activity

    18 months

Other Outcomes (2)

  • To determine cerebrospinal fluid (CSF) concentrations EPZ-5676 in pediatric patients receiving EPZ-5676 by CIV infusion

    18 months

  • Analysis of tumor cells for somatic mutations as potential predictors of response

    18 months

Study Arms (1)

EPZ-5676

EXPERIMENTAL

EPZ-5676 Dose escalation and expansion cohorts

Drug: EPZ-5676

Interventions

EPZ-5676DRUG

28-day continuous IV infusion of each 28-day cycle, given until disease progression or unacceptable toxicity develops.

Also known as: EPZ5676, DOT1L
EPZ-5676

Eligibility Criteria

Age3 Months - 18 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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:
  • 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)
  • +6 more criteria

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Childrens Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

University of California San Francisco Medical Center-Parnassus

San Francisco, California, 94143, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Emory Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

The Hospital for Sick Kids

Toronto, Ontario, Canada

Location

MeSH Terms

Conditions

LeukemiaLeukemia, Myeloid, AcutePrecursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

EPZ-5676

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLeukemia, MyeloidLeukemia, LymphoidLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Study Officials

  • Neal Shukla, MD

    Memorial Sloan Kettering Cancer Center

    PRINCIPAL INVESTIGATOR

  • Lia Gore, MD

    Children's Hospital Colorado

    PRINCIPAL INVESTIGATOR

  • Pat Brown, MD

    Johns Hopkins University

    PRINCIPAL INVESTIGATOR

  • Lewis Silverman, MD

    Dana Farber

    PRINCIPAL INVESTIGATOR

  • Maureen O'Brien, MD

    Children's Hospital Medical Center, Cincinnati

    PRINCIPAL INVESTIGATOR

  • Jim A Whitlock, MD

    Hospital of Sick Kids

    PRINCIPAL INVESTIGATOR

  • Cynthia Wetmore, MD PhD

    Emory Children's Healthcare of Atlanta

    PRINCIPAL INVESTIGATOR

  • Mignon Loh, MD

    University of California, San Francisco

    PRINCIPAL INVESTIGATOR

  • Paul Gaynon, MD

    Children's Hospital Los Angeles

    PRINCIPAL INVESTIGATOR

  • Todd Cooper, MD

    Seattle Children's Hospital

    PRINCIPAL INVESTIGATOR

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

May 11, 2014

First Posted

May 20, 2014

Study Start

May 1, 2014

Primary Completion

May 1, 2016

Study Completion

June 1, 2016

Last Updated

June 18, 2023

Record last verified: 2020-05

Locations

US(8)CA(1)