NCT02238522

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).

Trial Health

30
At Risk

Trial Health Score

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

Trial has exceeded expected completion date
Timeline
Completed

Started Oct 2014

Typical duration for phase_1

Geographic Reach
1 country

4 active sites

Status
withdrawn

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

First Submitted

Initial submission to the registry

August 28, 2014

Completed
15 days until next milestone

First Posted

Study publicly available on registry

September 12, 2014

Completed
19 days until next milestone

Study Start

First participant enrolled

October 1, 2014

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2016

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2017

Completed
Last Updated

November 13, 2014

Status Verified

November 1, 2014

Enrollment Period

1.7 years

First QC Date

August 28, 2014

Last Update Submit

November 12, 2014

Conditions

Lymphoproliferative MalignanciesAcute Myeloid Leukemia

Keywords

Chronic lymphocytic leukemiaB-prolymphocytic leukemiaNon-Hodgkin's lymphomafollicular lymphomamantle cell lymphomamarginal zone lymphomasmall lymphocytic lymphomadiffuse large B-cell lymphomaunclassifiable lymphomaT-cell lymphomaRichter's syndromeWaldenström's macroglobulinemia

Outcome Measures

Primary Outcomes (4)

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

    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

    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

    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

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

Secondary Outcomes (2)

  • 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

    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

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

Study Arms (2)

Dose Escalation Stage - ZEN003365

EXPERIMENTAL

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

Drug: ZEN003365

Dose Expansion Stage - ZEN003365

EXPERIMENTAL

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

Drug: ZEN003365

Interventions

ZEN003365DRUG
Dose Escalation Stage - ZEN003365Dose Expansion Stage - ZEN003365

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • +1 more criteria

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Willamette Valley Cancer Institute and Research Center

Springfield, Oregon, 97477, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, AcuteLeukemia, Lymphocytic, Chronic, B-CellLeukemia, Prolymphocytic, B-CellLymphoma, Non-HodgkinLymphoma, FollicularLymphoma, Mantle-CellLymphoma, B-Cell, Marginal ZoneLymphoma, Large B-Cell, DiffuseLymphoma, T-CellWaldenstrom Macroglobulinemia

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLeukemia, B-CellLeukemia, LymphoidLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLeukemia, ProlymphocyticLymphomaLymphoma, B-CellNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic Disorders
0

Study Design

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

Study Record Dates

First Submitted

August 28, 2014

First Posted

September 12, 2014

Study Start

October 1, 2014

Primary Completion

June 1, 2016

Study Completion

January 1, 2017

Last Updated

November 13, 2014

Record last verified: 2014-11

Locations

US(4)