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

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02238522
• Other study ID #: ZEN-ONC3365-101
• Status: Withdrawn
• Phase: Phase 1
• First received: August 28, 2014
• Last updated: November 12, 2014
• Start date: October 2014
• Est. completion date: January 2017

Study information

• Verified date: November 2014
• Source: Zenith Epigenetics Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2017
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphoproliferative Malignancies
• Neoplasms

Intervention

Drug:
• ZEN003365

Locations

Country	Name	City	State
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Willamette Valley Cancer Institute and Research Center	Springfield	Oregon
United States	Washington University School of Medicine	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Zenith Epigenetics Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Yes
Primary	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	Yes
Primary	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)	No
Primary	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)	Yes
Secondary	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)	No
Secondary	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)	No