Study of a Novel BET Inhibitor FT-1101 in Patients With Relapsed or Refractory Hematologic Malignancies

Sponsor
Forma Therapeutics, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02543879
Collaborator
(none)
94
8
4
42
11.8
0.3

Study Details

Study Description

Brief Summary

This is an open-label, multicenter, dose-escalation Phase 1/1b study in patients with acute myelogenous leukemia (AML)/MDS or non-Hodgkin Lymphoma (NHL), intended to investigate safety, pharmacokinetics, and the pharmacodynamic effects of FT-1101 administered via one or more intermittent dosing schedules alone and in combination with azacitidine. Once the MTD has been established for a treatment cohort, up to 20 additional patients may be enrolled in up to 4 expansion cohorts each of select populations of patients with either AML/MDS or NHL at the recommended dose for future studies to confirm safety.

Study Design

Study Type:
Interventional
Actual Enrollment :
94 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/1b Dose Escalation, Multicenter, Open-label, Safety, Pharmacokinetic and Pharmacodynamic Study of FT-1101 as a Single Agent and in Combination With Azacitidine in Patients With Relapsed or Refractory Hematologic Malignancies
Study Start Date :
Sep 1, 2015
Actual Primary Completion Date :
Mar 1, 2019
Actual Study Completion Date :
Mar 1, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose Escalation FT-1101

Following a 3+3 dose escalation strategy, the first cohort of patients will be administered FT-1101 at 10 mg, oral capsules, once weekly on a continuous basis. Subsequent cohorts dose and frequency will be determined by investigators and sponsor following observations of previous cohorts. Dose escalation will continue until the MTD is determined.

Drug: FT-1101
FT-1101 will be supplied as 5 mg, 20 mg or 100 mg capsules and will be administered per the protocol defined frequency and dose level
Other Names:
  • FT1101
  • Experimental: Dose Expansion FT-1101

    Once the MTD is determined, the Recommended Phase 2 Dose (RP2D) will be identified. 3 Expansion cohorts of up to 20 patients each will be treated with the RP2D of FT-1101

    Drug: FT-1101
    FT-1101 will be supplied as 5 mg, 20 mg or 100 mg capsules and will be administered per the protocol defined frequency and dose level
    Other Names:
  • FT1101
  • Experimental: Dose Escalation FT-1101 + azacitidine

    Following a 3+3 dose escalation strategy, the first cohort of AML/MDS patients will be administered FT-1101 at approximately 50% or lower than the MTD identified for the single agent FT-1101. Subsequent cohorts dose will be determined by investigators and sponsor following observations of previous cohorts. Dose escalation will not exceed the dose determined to be the single agent MTD for that schedule.

    Drug: FT-1101
    FT-1101 will be supplied as 5 mg, 20 mg or 100 mg capsules and will be administered per the protocol defined frequency and dose level
    Other Names:
  • FT1101
  • Drug: Azacitidine
    Azacitidine will be administered per site's standard of care

    Experimental: Dose Expansion FT-1101 + azacitidine

    Once the MTD is determined, the Recommended Phase 2 Dose (RP2D) will be identified. 1 Expansion cohorts of up to 20 AML/MDS patients each will be treated with the RP2D of FT-1101 in combination with azacitidine.

    Drug: FT-1101
    FT-1101 will be supplied as 5 mg, 20 mg or 100 mg capsules and will be administered per the protocol defined frequency and dose level
    Other Names:
  • FT1101
  • Drug: Azacitidine
    Azacitidine will be administered per site's standard of care

    Outcome Measures

    Primary Outcome Measures

    1. Maximum Tolerated Dose (MTD) [Within first 4 weeks of treatment]

    2. Dose Limiting Toxicities (DLT) [Within first 4 weeks of treatment]

    3. Recommended Phase 2 Dose (RP2D) [Participants to be followed for duration of participation, an expected average of 12 weeks]

    Secondary Outcome Measures

    1. Area under the plasma concentration versus time curve (AUC) [PK collected at multiple visits during the first 30 days of treatment]

    2. Peak Plasma Concentration (Cmax) [PK collected at multiple visits during the first 30 days of treatment]

    3. Time of peak plasma concentration (TMax) [PK collected at multiple visits during the first 30 days of treatment]

    4. Time for half of the drug to be absent in blood stream following dose (T 1/2) [PK collected at multiple visits during the first 30 days of treatment]

    5. Rate at which drug is removed from blood stream (CL/F) [PK collected at multiple visits during the first 30 days of treatment]

    6. Rate of drug distribution within the blood stream (Vd/F) [PK collected at multiple visits during the first 30 days of treatment]

    7. Observe patients for any evidence of anti-leukemic or anti-myelodysplastic activity of FT-1101 [Assessed for duration of participation, an expected average of 12 weeks]

    Other Outcome Measures

    1. Assessment of on-target activity of FT-1101, as determined by changes in PD biomarkers in bone marrow aspirates and/or peripheral blood [Assessed for duration of participation, an expected average of 12 weeks]

    2. To determine if there is any correlation between cancer-associated genetic alterations with response [Assessed for duration of participation, an expected average of 12 weeks]

    3. To evaluate PK/PD relationships in dose-escalation and dose-expansion cohorts [Assessed for duration of participation, an expected average of 12 weeks]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:
    • Single agent (SA) Dose Escalation: Histologically or cytologically proven acute leukemia or high-risk MDS as defined by the World Health Organization (WHO) criteria and IPSS-R, respectively, that is relapsed or refractory (R/R) to standard therapy or for whom standard treatments are contraindicated, OR

    • Mature B-Cell non-Hodgkin Lymphoma that is Relapsed/Refractory to standard therapy

    • AML SA expansion group 1: histologically or cytologically proven AML with a FLT3 ITD or TKD mutation previously determined by local testing that is R/R to standard therapy or for whom standard treatments are contraindicated

    • AML SA expansion group 2: histologically or cytologically proven AML with intermediate or unfavorable risk cytogenetics in the absence of a detectable FLT3 ITD or TKD mutation as previously determined by local testing that is R/R to standard therapy or for whom standard treatments are contraindicated

    • NHL SA expansion: Mature B-cell NHL with the following histologies: primary mediastinal lymphoma, DLBCL, and B-cell lymphoma not specified that is R/R to standard therapy and for whom standard treatments are contraindicated or unavailable

    • AML/MDS combination treatment (dose escalation and expansion): histologically or cytologically proven AML or MDS as defined by WHO criteria and IPSS-R, respectively, that is: R/R to standard therapy, or AML: who are unfit for, or unwilling to receive standard induction therapy, or MDS: eligible to receive azacitidine

    • Patients ≥ 18 years old

    • Good kidney and liver function

    • No prior organ allograft

    • For fertile men and women, agreement to use effective contraceptive methods duration of study participation and 90 days after

    Key Exclusion Criteria:
    • History of prior malignancy unless disease free for > or equal to 12 months or considered surgically cured.

    • Patients with symptomatic central nervous system (CNS) metastases or other tumor location (such as spinal cord compression, other compressive mass, uncontrolled painful lesion, bone fracture, etc.) necessitating an urgent therapeutic intervention, palliative care, surgery or radiation therapy

    • Treatment with major surgery (requiring general anesthesia) within one month prior to study entry

    • Previous treatment with any prior BET inhibitor therapy

    • Patients unable to swallow oral medications, or patients with gastrointestinal conditions (e.g. malabsorption, gastric or small bowel resection, etc.) deemed to jeopardize intestinal absorption

    • Congestive heart failure (New York Heart Association Class III or IV) or unstable angina pectoris. Previous history of myocardial infarction within 1 year prior to study entry, uncontrolled hypertension or uncontrolled arrhythmias

    • Pulmonary disease (e.g. COPD, asthma, etc) that is not controlled (moderate to severe symptoms) with current medication

    • Known HIV positivity

    • Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Cedars Sinai Los Angeles California United States 90048
    2 Florida Cancer Specialists Sarasota Florida United States 34232
    3 Moffitt Cancer Center Tampa Florida United States 23985
    4 Northwestern University Chicago Illinois United States 60611
    5 University of Maryland, Greenebaum Comprehensive Cancer Center Baltimore Maryland United States 21201
    6 Levine Cancer Institute Charlotte North Carolina United States 28204
    7 Sarah Cannon Research Institute Nashville Tennessee United States 37203
    8 MD Anderson Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • Forma Therapeutics, Inc.

    Investigators

    • Study Director: Patrick Kelly, MD, Forma Therapeutics, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Forma Therapeutics, Inc.
    ClinicalTrials.gov Identifier:
    NCT02543879
    Other Study ID Numbers:
    • 1101-HEM-101
    First Posted:
    Sep 7, 2015
    Last Update Posted:
    Jun 26, 2019
    Last Verified:
    Jun 1, 2019

    Study Results

    No Results Posted as of Jun 26, 2019