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

NCT02543879

Description:

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.

Related Conditions:
  • Acute Leukemia
  • Acute Myeloid Leukemia
  • B-Cell Non-Hodgkin Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Mature B-Cell Lymphoma/Leukemia
  • Mediastinal Large B-Cell Lymphoma
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 1101-HEM-101
  • NCT ID: NCT02543879

Conditions

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

Interventions

DrugSynonymsArms
FT-1101FT1101Dose Escalation FT-1101
AzacitidineDose Escalation FT-1101 + azacitidine

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation FT-1101ExperimentalFollowing 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.
  • FT-1101
Dose Expansion FT-1101ExperimentalOnce 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
  • FT-1101
Dose Escalation FT-1101 + azacitidineExperimentalFollowing 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.
  • FT-1101
  • Azacitidine
Dose Expansion FT-1101 + azacitidineExperimentalOnce 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.
  • FT-1101
  • Azacitidine

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD)
Time Frame:Within first 4 weeks of treatment
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Area under the plasma concentration versus time curve (AUC)
Time Frame:PK collected at multiple visits during the first 30 days of treatment
Safety Issue:
Description:
Measure:Peak Plasma Concentration (Cmax)
Time Frame:PK collected at multiple visits during the first 30 days of treatment
Safety Issue:
Description:
Measure:Time of peak plasma concentration (TMax)
Time Frame:PK collected at multiple visits during the first 30 days of treatment
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Rate of drug distribution within the blood stream (Vd/F)
Time Frame:PK collected at multiple visits during the first 30 days of treatment
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Forma Therapeutics, Inc.

Trial Keywords

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

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