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AzTrials

Acute Myeloid LeukemiaPhase 1NCT01684150

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

A Phase 1 study testing EPZ-5676 in people with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by Epizyme, Inc. at 8 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 90 years
What is being tested?
EPZ-5676
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
8 sitesin 3 countries
Study dates
Sep 2012to Feb 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • > 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
  • Able and willing to give written informed consent.
  • Life expectancy of at least 3 months

Who cannot join

  • 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.
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  • Known, active (symptomatic) involvement of the central nervous system by leukemia.
  • On immunosuppressive therapy.
  • Known active infection.
  • Pregnant or nursing females.

Trial locations and contacts

8 sites in 3 countries.

8 sites in 3 countries

United States6 sites

  • Northwestern University

    Chicago, Illinois, 60611

  • Duke University Health System

    Durham, North Carolina, 27710

  • UT MD Anderson Cancer

    Houston, Texas, 77030

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Mayo Clinic Scottsdale-Phoenix

    Scottsdale, Arizona, 85259

Other trials in United States

Germany1 site

  • Universitätsklinikum Ulm

    Ulm, 89081

Other trials in Germany

Netherlands1 site

  • Erasmus University Medical Center

    Rotterdam

Other trials in Netherlands

About this study

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

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).

Read the 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).

Being tested
EPZ-5676
Keywords
Leukemia, Advanced hematologic malignancies, Epizyme, Phase 1, Mixed Lineage Leukemia (MLL)
Medical subject headings
Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Myelodysplastic Syndromes, Myeloproliferative Disorders, Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EPZ-5676Drug

    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.

Study groups in NCT01684150
Study groupRoleWhat they receive
EPZ-5676 Extension cohortExperimentalNot described
Receives: Drug: EPZ-5676

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: up to 12 months

Secondary outcomes (5)

  1. Pharmacokinetic profile of EPZ-5676

    analysis of Cmax, AUC and steady state concentration

    Measured: up to 24 months

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

    Evaluation of adverse events, vital signs, physical examination, 12-lead ECG, and laboratory assessments

    Measured: up to 24 months

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

    Evaluation of response by standard criteria for AML or ALL

    Measured: up to 24 months

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

    Measured: up to 24 months

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

    Measured: up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Sep 2012 (estimated)
  2. Study startSep 2012
  3. Primary completionNov 2015
  4. Study completionFeb 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01684150
Sponsor's protocol ID
EPZ-5676-12-001
Other IDs
2013-002355-15
Status last verified
Mar 2024
First submitted
6 Sep 2012
Last updated
26 Mar 2024
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 29724899

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing EPZ-5676 in people with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by Epizyme, Inc. at 8 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States, Germany, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01684150, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2024.

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