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

NCT02543879 | Completed Phase 1

• 1 other identifier: 1101-HEM-101
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 8

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.

Conditions

Acute Myeloid Leukemia; Acute Myelogenous Leukemia; Myelodysplastic Syndrome; Non-Hodgkin Lymphoma

Keywords

AML; BET Inhibitor; FT-1101; Acute Leukemia; Myelodysplastic Syndrome; NHL; Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose (MTD)

  Within first 4 weeks of treatment

• Dose Limiting Toxicities (DLT)

  Within first 4 weeks of treatment

• Recommended Phase 2 Dose (RP2D)

  Participants to be followed for duration of participation, an expected average of 12 weeks

Secondary Outcomes (7)

• Area under the plasma concentration versus time curve (AUC)

  PK collected at multiple visits during the first 30 days of treatment

• Peak Plasma Concentration (Cmax)

  PK collected at multiple visits during the first 30 days of treatment

• Time of peak plasma concentration (TMax)

  PK collected at multiple visits during the first 30 days of treatment

• 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

• Rate at which drug is removed from blood stream (CL/F)

  PK collected at multiple visits during the first 30 days of treatment

Other Outcomes (3)

• 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

• 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

• To evaluate PK/PD relationships in dose-escalation and dose-expansion cohorts

  Assessed for duration of participation, an expected average of 12 weeks

Study Arms (4)

Dose Escalation FT-1101

EXPERIMENTAL

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

Dose Expansion FT-1101

EXPERIMENTAL

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

Dose Escalation FT-1101 + azacitidine

EXPERIMENTAL

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; Drug: Azacitidine

Dose Expansion FT-1101 + azacitidine

EXPERIMENTAL

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; Drug: Azacitidine

Interventions

FT-1101 DRUG

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

Also known as: FT1101

Dose Escalation FT-1101; Dose Escalation FT-1101 + azacitidine; Dose Expansion FT-1101; Dose Expansion FT-1101 + azacitidine

Azacitidine DRUG

Azacitidine will be administered per site's standard of care

Dose Escalation FT-1101 + azacitidine; Dose Expansion FT-1101 + azacitidine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Forma Therapeutics, Inc.: lead

Study Sites (8)

Cedars Sinai

Los Angeles, California, 90048, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Moffitt Cancer Center

Tampa, Florida, 23985, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Maryland, Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Crymes A, Evans MG, Jeyakumar D, Lou JJ, Zhao X, Rezk SA. Acute Myeloid Leukemia (AML) With T-Cell Differentiation Arising From Chronic Myelomonocytic Leukemia (CMML). Case Rep Hematol. 2024 Dec 14;2024:5584297. doi: 10.1155/crh/5584297. eCollection 2024.

  PMID: 39734743 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Lymphoma, Non-Hodgkin

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Patrick Kelly, MD

  Forma Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: September 1, 2015
• First Posted: September 7, 2015
• Study Start: September 1, 2015
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2019
• Last Updated: November 21, 2023

Record last verified: 2023-11

Locations

US (8)