Clinical trial NCT02238522: 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
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: 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
Lead sponsor: Zenith Epigenetics
Sponsor class: INDUSTRY
First posted: 2014-09-12
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Dose escalation stage - The safety of orally administered ZEN003365, assessed by frequency of adverse events, including worsening of medical conditions/diseases
timeFrame: From Day 1 Cycle 1 through the last day of treatment with ZEN003365 (12 weeks, average)
measure: Dose escalation stage - To characterize the DLTs of orally administered ZEN003365, using NCI CTCAE v4.03
timeFrame: The first 25 days of at least 12 doses of ZEN003365
measure: 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
timeFrame: From Day 1 Cycle 1 through the last day of treatment with ZEN003365 (12 weeks, average)
measure: 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
timeFrame: From Day 1 Cycle 1 through the last day of treatment with ZEN003365 (12 weeks, average)
Secondary outcomes:
measure: 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
timeFrame: From Day 1 Cycle 1 through the last day of treatment with ZEN003365 (12 weeks, average)
measure: 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
timeFrame: From Screening Visit through 40 days after the last day of treatment with ZEN003365 (19 weeks, average)
Other outcomes:
Locations:
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Springfield
country: United States
facility: Willamette Valley Cancer Institute and Research Center
state: Oregon
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
Study officials:
References: