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

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ClinicalTrials.gov Identifier: NCT02543879
Recruitment Status : Completed
First Posted : September 7, 2015
Last Update Posted : June 26, 2019
Sponsor:
Information provided by (Responsible Party):
Forma Therapeutics, Inc.

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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Acute Myelogenous Leukemia Myelodysplastic Syndrome Non-Hodgkin Lymphoma Drug: FT-1101 Drug: Azacitidine Phase 1

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Study Type : Interventional  (Clinical Trial)
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 : September 2015
Actual Primary Completion Date : March 2019
Actual Study Completion Date : March 2019


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 Name: 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 Name: 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 Name: 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 Name: FT1101

Drug: Azacitidine
Azacitidine will be administered per site's standard of care




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) [ Time Frame: Within first 4 weeks of treatment ]
  2. Dose Limiting Toxicities (DLT) [ Time Frame: Within first 4 weeks of treatment ]
  3. Recommended Phase 2 Dose (RP2D) [ Time Frame: 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) [ Time Frame: PK collected at multiple visits during the first 30 days of treatment ]
  2. Peak Plasma Concentration (Cmax) [ Time Frame: PK collected at multiple visits during the first 30 days of treatment ]
  3. Time of peak plasma concentration (TMax) [ Time Frame: 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) [ Time Frame: PK collected at multiple visits during the first 30 days of treatment ]
  5. Rate at which drug is removed from blood stream (CL/F) [ Time Frame: PK collected at multiple visits during the first 30 days of treatment ]
  6. Rate of drug distribution within the blood stream (Vd/F) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Assessed for duration of participation, an expected average of 12 weeks ]
  3. To evaluate PK/PD relationships in dose-escalation and dose-expansion cohorts [ Time Frame: Assessed for duration of participation, an expected average of 12 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02543879


Locations
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United States, California
Cedars Sinai
Los Angeles, California, United States, 90048
United States, Florida
Florida Cancer Specialists
Sarasota, Florida, United States, 34232
Moffitt Cancer Center
Tampa, Florida, United States, 23985
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Maryland
University of Maryland, Greenebaum Comprehensive Cancer Center
Baltimore, Maryland, United States, 21201
United States, North Carolina
Levine Cancer Institute
Charlotte, North Carolina, United States, 28204
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Forma Therapeutics, Inc.
Investigators
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Study Director: Patrick Kelly, MD Forma Therapeutics, Inc.

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Responsible Party: Forma Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02543879     History of Changes
Other Study ID Numbers: 1101-HEM-101
First Posted: September 7, 2015    Key Record Dates
Last Update Posted: June 26, 2019
Last Verified: June 2019

Keywords provided by Forma Therapeutics, Inc.:
AML
BET Inhibitor
FT-1101
Acute Leukemia
Myelodysplastic Syndrome
NHL
Non-Hodgkin Lymphoma

Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Lymphoma, Non-Hodgkin
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Lymphoma
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors