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Open-label Study of FT-2102 With or Without Azacitidine or Cytarabine in Patients With AML or MDS With an IDH1 Mutation

NCT02719574

Description:

This Phase 1/2 study will evaluate the safety, efficacy, PK, and PD of FT-2102 as a single agent or in combination with azacitidine or cytarabine. The Phase 1 stage of the study is split into 2 distinct parts: a dose escalation part, which will utilize an open-label design of FT-2102 (single agent) and FT-2102 + azacitidine (combination agent) administered via one or more intermittent dosing schedules followed by a dose expansion part. The dose expansion part will enroll patients in up to 5 expansion cohorts, exploring single-agent FT-2102 activity as well as combination activity with azacitidine or cytarabine. Following the completion of the relevant Phase 1 cohorts, Phase 2 will begin enrollment. Patients will be enrolled across 6 different cohorts, examining the effect of FT-2102 (as a single agent) and FT-2102 + azacitidine (combination) on various AML/MDS disease states.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Open-label Study of FT-2102 With or Without Azacitidine or Cytarabine in Patients With AML or MDS With an IDH1 Mutation
  • Official Title: A Phase 1/2, Multicenter, Open-label Study of FT-2102 as a Single Agent and in Combination With Azacitidine or Cytarabine in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome With an IDH1 Mutation

Clinical Trial IDs

  • ORG STUDY ID: 2102-HEM-101
  • NCT ID: NCT02719574

Conditions

  • Acute Myeloid Leukemia
  • Acute Myelogenous Leukemia
  • Myelodysplastic Syndrome

Interventions

DrugSynonymsArms
FT-2102PH1 Dose Escalation & Expansion FT-2102
AzacitidineVidazaPH1 Esc. and Exp. FT-2102+Azacitidine
CytarabinePH1 Esc. and Exp. FT-2102+Cytarabine

Purpose

This Phase 1/2 study will evaluate the safety, efficacy, PK, and PD of FT-2102 as a single agent or in combination with azacitidine or cytarabine. The Phase 1 stage of the study is split into 2 distinct parts: a dose escalation part, which will utilize an open-label design of FT-2102 (single agent) and FT-2102 + azacitidine (combination agent) administered via one or more intermittent dosing schedules followed by a dose expansion part. The dose expansion part will enroll patients in up to 5 expansion cohorts, exploring single-agent FT-2102 activity as well as combination activity with azacitidine or cytarabine. Following the completion of Phase 1, Phase 2 will begin enrollment. Patients will be enrolled across 6 different cohorts, examining the effect of FT-2102 (as a single agent) and FT-2102 + azacitidine (combination) on various AML/MDS disease states.

Trial Arms

NameTypeDescriptionInterventions
PH1 Dose Escalation & Expansion FT-2102Experimental
  • FT-2102
PH1 Esc. and Exp. FT-2102+AzacitidineExperimental
  • FT-2102
  • Azacitidine
PH1 Esc. and Exp. FT-2102+CytarabineExperimental
  • FT-2102
  • Cytarabine
PH2 Cohort 1 FT-2102 Single AgentExperimentalAt the completion of Phase 1, Phase 2 Cohort 1 will commence enrollment wherein patients with relapsed or refractory (R/R) AML will be treated with the RP2D of FT-2102 as a single-agent.
  • FT-2102
PH2 Cohort 2 FT-2102 Single AgentExperimentalIn Phase 2 Cohort 2, patients with AML/ MDS in morphologic complete remission or complete remission with incomplete blood count recovery (CR/CRi) after cytotoxic-containing induction therapy with residual IDH-R132 mutation will be treated at the RP2D of FT-2102 as a single-agent.
  • FT-2102
PH2 Cohort 3 FT-2102 Single AgentExperimentalIn Phase 2 Cohort 3, patients with R/R AML/MDS, previously treated with an IDH1 inhibitor will be treated at the RP2D of FT-2102 as a single-agent.
  • FT-2102
PH2 Cohort 4 FT-2102+AzacitidineExperimentalIn Phase 2 Cohort 4, patients with R/R AML/MDS that are naïve to prior hypomethylating therapy and IDH1 inhibitor therapy will be treated with the RP2D of FT-2102 in combination with azacitidine.
  • FT-2102
  • Azacitidine
PH2 Cohort 5 FT-2102+AzacitidineExperimentalIn Phase 2 Cohort 5, patients with R/R AML/MDS that have inadequately responded or have progressed immediately proceeding hypomethylating therapy will be treated with the RP2D of FT-2102 in combination with azacitidine.
  • FT-2102
  • Azacitidine
PH2 Cohort 6 FT-2102+AzacitidineExperimentalIn Phase 2 Cohort 6, patients with R/R AML/MDS that have been previously treated with single-agent IDH1 inhibitor therapy as their last therapy prior to study enrollment will be treated with the RP2D of FT-2102 in combination with azacitidine.
  • FT-2102
  • Azacitidine

Eligibility Criteria

        Inclusion Criteria:

          -  Pathologically proven acute myeloid leukemia (AML) or intermediate, high-risk, or very
             high risk Myelodysplastic Syndrome (MDS) as defined by the World Health Organization
             (WHO) criteria or Revised International Prognostic Scoring System (IPSS-R) which is
             relapsed or refractory (R/R) to standard therapy and/or for which standard therapy is
             contraindicated or which has not adequately responded to standard therapy.

          -  Patients must have documented IDH1-R132 gene-mutated disease as evaluated by the site

          -  Good performance status

          -  Good kidney and liver function

        Exclusion Criteria:

          -  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

          -  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

          -  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 Doses (MTDs) or Maximum Evaluated Doses (MEDs) [Phase 1]
Time Frame:Within first 4 weeks of treatment
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Area under the plasma concentration versus time curve (AUC) [Phase 1 and Phase 2]
Time Frame:Blood samples for PK analysis collected at multiple visits during the first 60 days of treatment and on day 1 of all cycles following the first 30 days
Safety Issue:
Description:
Measure:Peak Plasma Concentration (Cmax) [Phase 1 and Phase 2]
Time Frame:Blood samples for PK analysis collected at multiple visits during the first 60 days of treatment and on day 1 of all cycles following the first 30 days
Safety Issue:
Description:
Measure:Time of peak plasma concentration Tmax [Phase 1 and Phase 2]
Time Frame:Blood samples for PK analysis collected at multiple visits during the first 60 days of treatment and on day 1 of all cycles following the first 30 days
Safety Issue:
Description:
Measure:Time for half of the drug to be absent in blood stream following dose (T 1/2) [Phase 1 and Phase 2]
Time Frame:Blood samples for PK analysis collected at multiple visits during the first 60 days of treatment and on day 1 of all cycles following the first 30 days
Safety Issue:
Description:
Measure:Rate at which drug is removed from blood stream (CL/F) [Phase 1 and Phase 2]
Time Frame:Blood samples for PK analysis collected at multiple visits during the first 60 days of treatment and on day 1 of all cycles following the first 30 days
Safety Issue:
Description:
Measure:Rate of drug distribution within the blood stream (Vd/F) [Phase 1 and Phase 2]
Time Frame:Blood samples for PK analysis collected at multiple visits during the first 60 days of treatment and on day 1 of all cycles following the first 30 days
Safety Issue:
Description:
Measure:Evidence of antileukemic or antimyelodysplastic activity of FT-2102 as determined by CR, CRi, MLFS, Marrow CR, PR, and SD as a single-agent or in combination with azacitidine or cytarabine [Phase 1]
Time Frame:As per IWG Response Assessment Guidelines for AML and MDS based on investigator's assessment on day 1 of each cycle through study completion
Safety Issue:
Description:
Measure:Incidence and severity of adverse events, clinical laboratory abnormalities, and changes in ECG parameters as assessed by CTCAE v4.0 as a single-agent or in combination with azacitidine [Phase 2]
Time Frame:Safety will be assessed from time of first dose through 28 days post last dose.
Safety Issue:
Description:
Measure:Additional measures of antileukemic or antimyelodysplastic activity as determined by CRh, Overall Response (OR), and Stable Disease of FT-2102 alone or in combination with azacitidine [Phase 2]
Time Frame:As per IWG Response Assessment Guidelines for AML and MDS based on investigator's assessment on day 1 of each cycle through study completion
Safety Issue:
Description:
Measure:Time to Response (TTR) [Phase 2]
Time Frame:From first dose of study drug through time of first response by blood recovery count, up to 30 weeks, on average
Safety Issue:
Description:
Measure:Duration of Response (DOR) [Phase 2]
Time Frame:From time of first response by blood recovery count through relapse, up to 30 weeks, on average
Safety Issue:
Description:
Measure:Event-Free Survival (EFS) [Phase 2]
Time Frame:From time of entry on study through progression, up to 30 weeks, on average
Safety Issue:
Description:
Measure:Overall Survival (OS) [Phase 2]
Time Frame:From time of entry on study through death or date last known alive at end of follow-up, up to 30 weeks, on average
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Forma Therapeutics, Inc.

Trial Keywords

  • AML
  • MDS
  • IDH1
  • IDH

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