Phase 1 Study Evaluating ZEN003365 in Relapsed/Refractory Lymphoproliferative Malignancies or Relapsed/Refractory AML

November 12, 2014 updated by: Zenith Epigenetics

Phase 1 Open-label Dose Escalation and Expansion Study of ZEN003365 in Subjects With Relapsed or Refractory Lymphoproliferative Malignancies or Acute Myeloid Leukemia

The purpose of this study is to determine safety, tolerability, dose limiting toxicities (DLT) and maximum tolerated dose (MTD) of ZEN003365 in patients with relapsed/refractory lymphoproliferative malignancies (LPM) or relapsed/refractory acute myeloid leukemia (AML).

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Study Type

Interventional

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • Oregon
      • Springfield, Oregon, United States, 97477
        • Willamette Valley Cancer Institute and Research Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Dose Escalation and Expansion Stages:

  • ECOG performance status ≤ 1 for LPM patients, ≤ 2 for AML patients
  • Age 18 years or older
  • Adverse events (AEs), except for alopecia, from any previous treatments must have recovered to eligibility levels from prior toxicity
  • Adequate renal, hepatic and coagulation function, as specified per protocol
  • Written informed consent granted prior to any study-specific screening procedures

LPM Patients:

  • Histologically confirmed lymphoproliferative malignancy
  • Have received prior protocol-specified disease-dependent prior treatments
  • Have measurable disease
  • Platelets ≥ 75,000/µL (≥50,000/µL if bone marrow involvement), absolute neutrophil count (ANC) ≥ 1,000/ µL, and hemoglobin (Hgb) ≥ 8 g/dL
  • Patients must have been off previous anticancer therapy for at least 3 weeks or 5 half-lives, whichever is longer, and the subject must have recovered to eligibility levels from prior toxicity

AML:

  • Refractory or relapsed AML patients, without curative intent, e.g., not a stem cell transplant candidate
  • Any prior chemotherapy must have been completed ≥ 2 weeks, any therapy with biologics must have been completed ≥ 4 weeks prior to day 1 of study treatment, and the participant must have recovered to eligibility levels from prior toxicity
  • Blast count ≤ 10,000/µL prior to initiation of therapy

Exclusion Criteria

Dose Escalation and Expansion Stages:

  • Prior exposure to a BET inhibitor
  • Prior allogeneic hematopoietic cell transplant
  • Chronic graft versus host disease
  • Known, active fungal, bacterial, and/or viral infection
  • Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
  • Current subdural hematoma
  • CNS or leptomeningeal metastases
  • Requirement for medications or agents known to be sensitive CYP3A4 substrate drugs, CYP3A4 substrate drugs with a narrow therapeutic range or to be strong inhibitors/inducers of CYP3A4
  • Requirement for immunosuppressive agents
  • Evidence of significant cardiovascular disease or significant screening ECG abnormalities
  • Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient.

AML patients:

  • Acute promyelocytic leukemia (APL)
  • Chronic myeloid leukemia (CML) in blast crisis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Escalation Stage - ZEN003365
ZEN003365 will be administered orally as a single agent, enrolling LPM patients and AML patients
Drug: ZEN003365
Experimental: Dose Expansion Stage - ZEN003365
ZEN003365 will be administered orally as a single agent, enrolling LPM patients and AML patients
Drug: ZEN003365

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Dose escalation stage - The safety of orally administered ZEN003365, assessed by frequency of adverse events, including worsening of medical conditions/diseases
Time Frame: From Day 1 Cycle 1 through the last day of treatment with ZEN003365 (12 weeks, average)
From Day 1 Cycle 1 through the last day of treatment with ZEN003365 (12 weeks, average)
Dose escalation stage - To characterize the DLTs of orally administered ZEN003365, using NCI CTCAE v4.03
Time Frame: The first 25 days of at least 12 doses of ZEN003365
The first 25 days of at least 12 doses of ZEN003365
Dose expansion stage - Preliminary evidence of the antitumor activity of orally administered ZEN003365 in selected patients, assessed by objective response, duration of objective response and progression-free survival
Time Frame: From Day 1 Cycle 1 through the last day of treatment with ZEN003365 (12 weeks, average)
From Day 1 Cycle 1 through the last day of treatment with ZEN003365 (12 weeks, average)
Dose expansion stage - The safety of orally administered ZEN003365, at the dose chosen based upon the dose escalation stage, assessed by frequency of adverse events, including worsening of medical conditions/diseases
Time Frame: From Day 1 Cycle 1 through the last day of treatment with ZEN003365 (12 weeks, average)
From Day 1 Cycle 1 through the last day of treatment with ZEN003365 (12 weeks, average)

Secondary Outcome Measures

Outcome Measure
Time Frame
Dose escalation stage - To characterize the pharmacokinetics (PK) of orally administered ZEN003365 in patients, using the following parameters: AUC, Tmax, Cmax, Cmin, pre-dose concentration, and accumulation ratio
Time Frame: From Day 1 Cycle 1 through the last day of treatment with ZEN003365 (12 weeks, average)
From Day 1 Cycle 1 through the last day of treatment with ZEN003365 (12 weeks, average)
Dose expansion stage - To characterize the PK of orally administered ZEN003365, at the dose chosen based upon the dose escalation stage, using the following parameters: AUC, Tmax, Cmax, Cmin, pre-dose concentration, and accumulation ratio
Time Frame: From Screening Visit through 40 days after the last day of treatment with ZEN003365 (19 weeks, average)
From Screening Visit through 40 days after the last day of treatment with ZEN003365 (19 weeks, average)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Zenith Epigenetics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2014

Primary Completion (Anticipated)

June 1, 2016

Study Completion (Anticipated)

January 1, 2017

Study Registration Dates

First Submitted

August 28, 2014

First Submitted That Met QC Criteria

September 9, 2014

First Posted (Estimate)

September 12, 2014

Study Record Updates

Last Update Posted (Estimate)

November 13, 2014

Last Update Submitted That Met QC Criteria

November 12, 2014

Last Verified

November 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZEN-ONC3365-101

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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