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

Primary Purpose

Lymphoproliferative Malignancies, Acute Myeloid Leukemia

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

ZEN003365

About this trial

This is an interventional treatment trial for Lymphoproliferative Malignancies focused on measuring Chronic lymphocytic leukemia, B-prolymphocytic leukemia, Non-Hodgkin's lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, small lymphocytic lymphoma, diffuse large B-cell lymphoma, unclassifiable lymphoma, T-cell lymphoma, Richter's syndrome, Waldenström's macroglobulinemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Washington University School of Medicine
Memorial Sloan Kettering Cancer Center
Willamette Valley Cancer Institute and Research Center
Sarah Cannon Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Dose Escalation Stage - ZEN003365

Dose Expansion Stage - ZEN003365

Arm Description

ZEN003365 will be administered orally as a single agent, enrolling LPM patients and AML patients

Outcomes

Primary Outcome Measures

Dose escalation stage - The safety of orally administered ZEN003365, assessed by frequency of adverse events, including worsening of medical conditions/diseases

Dose escalation stage - To characterize the DLTs of orally administered ZEN003365, using NCI CTCAE v4.03

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

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

Secondary Outcome Measures

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

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

Full Information

NCT ID

NCT02238522

First Posted

August 28, 2014

Last Updated

November 12, 2014

Sponsor

Zenith Epigenetics

1. Study Identification

Unique Protocol Identification Number

NCT02238522

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2014

Overall Recruitment Status

Withdrawn

Study Start Date

October 2014 (undefined)

Primary Completion Date

June 2016 (Anticipated)

Study Completion Date

January 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Zenith Epigenetics

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lymphoproliferative Malignancies, Acute Myeloid Leukemia

Keywords

Chronic lymphocytic leukemia, B-prolymphocytic leukemia, Non-Hodgkin's lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, small lymphocytic lymphoma, diffuse large B-cell lymphoma, unclassifiable lymphoma, T-cell lymphoma, Richter's syndrome, Waldenström's macroglobulinemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dose Escalation Stage - ZEN003365

Arm Type

Experimental

Arm Description

ZEN003365 will be administered orally as a single agent, enrolling LPM patients and AML patients

Arm Title

Dose Expansion Stage - ZEN003365

Arm Type

Experimental

Arm Description

ZEN003365 will be administered orally as a single agent, enrolling LPM patients and AML patients

Intervention Type

Drug

Intervention Name(s)

ZEN003365

Primary Outcome Measure Information:

Title

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)

Title

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

Title

Time Frame

From Day 1 Cycle 1 through the last day of treatment with ZEN003365 (12 weeks, average)

Title

Time Frame

From Day 1 Cycle 1 through the last day of treatment with ZEN003365 (12 weeks, average)

Secondary Outcome Measure Information:

Title

Time Frame

From Day 1 Cycle 1 through the last day of treatment with ZEN003365 (12 weeks, average)

Title

Time Frame

From Screening Visit through 40 days after the last day of treatment with ZEN003365 (19 weeks, average)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Facility Information:

Facility Name

Washington University School of Medicine

City

St. Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

Memorial Sloan Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

Willamette Valley Cancer Institute and Research Center

City

Springfield

State/Province

Oregon

ZIP/Postal Code

97477

Country

United States

Facility Name

Sarah Cannon Research Institute

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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