Phase 1 Study Evaluating ZEN003365 in Relapsed/Refractory Lymphoproliferative Malignancies or Relapsed/Refractory AML
Phase 1
Withdrawn
- Conditions
- Lymphoproliferative MalignanciesAcute Myeloid Leukemia
- Interventions
- Registration Number
- NCT02238522
- Lead Sponsor
- Zenith Epigenetics
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
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
Exclusion Criteria
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Dose Escalation Stage - ZEN003365 ZEN003365 ZEN003365 will be administered orally as a single agent, enrolling LPM patients and AML patients Dose Expansion Stage - ZEN003365 ZEN003365 ZEN003365 will be administered orally as a single agent, enrolling LPM patients and AML patients
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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)
Trial Locations
- Locations (4)
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Washington University School of Medicine
🇺🇸St. Louis, Missouri, United States
Willamette Valley Cancer Institute and Research Center
🇺🇸Springfield, Oregon, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States