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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

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ClinicalTrials.gov Identifier: NCT02719574
Recruitment Status : Recruiting
First Posted : March 25, 2016
Last Update Posted : December 5, 2019
Sponsor:
Information provided by (Responsible Party):
Forma Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE March 21, 2016
First Posted Date  ICMJE March 25, 2016
Last Update Posted Date December 5, 2019
Study Start Date  ICMJE April 2016
Estimated Primary Completion Date April 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 3, 2019)
  • Maximum Tolerated Doses (MTDs) or Maximum Evaluated Doses (MEDs) [Phase 1] [ Time Frame: Within first 4 weeks of treatment ]
  • Number of Participants with a Dose Limiting Toxicity (DLT) [Phase 1] [ Time Frame: Within first 4 weeks of treatment ]
  • Doses recommended for future studies [Phase 1] [ Time Frame: Within first 4 weeks of treatment ]
  • Complete Response (CR and CRh) Rate of FT-2102 (olutasidenib) single-agent or in combination with Azacitidine in patients with AML/MDS [Phase 2 Cohorts 1, 3-8] [ Time Frame: As per modified IWG Response Assessment Guidelines for AML and MDS based on investigator's assessment on day 1 of each cycle through study completion ]
  • 4-Month Relapse Free Survival (RFS) of FT-2102 (olutasidenib) single-agent [Phase 2 Cohort 2] [ Time Frame: From time of entry on study through progression, up to 30 weeks, on average ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 21, 2016)
  • Maximum Tolerated Doses (MTDs) [ Time Frame: Within first 4 weeks of treatment ]
  • Dose LImiting Toxicities (DLTs) [ Time Frame: Within first 4 weeks of treatment ]
  • Doses recommended for future studies [ Time Frame: Within first 4 weeks of treatment ]
Change History Complete list of historical versions of study NCT02719574 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 3, 2019)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • Evidence of antileukemic or antimyelodysplastic activity of FT-2102 (olutasidenib) as determined by CR, CRh, CRi, MLFS, Marrow CR, PR, and SD as a single-agent or in combination with azacitidine or cytarabine [Phase 1] [ Time Frame: As per modified IWG Response Assessment Guidelines for AML and MDS based on investigator's assessment on day 1 of each cycle through study completion ]
  • 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. ]
  • Additional measures of antileukemic or antimyelodysplastic activity as determined by CRi, MLFS, Marrow CR, PR, Overall Response (OR), and Stable Disease (SD) of FT-2102 (olutasidenib) alone or in combination with azacitidine [Phase 2] [ Time Frame: As per modified IWG Response Assessment Guidelines for AML and MDS based on investigator's assessment on day 1 of each cycle through study completion ]
  • 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 ]
  • 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 ]
  • Event-Free Survival (EFS) [Phase 2] [ Time Frame: From time of entry on study through progression, up to 30 weeks, on average ]
  • 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 ]
  • Relapse Free Survival (RFS) [Phase 2] [ Time Frame: From time of entry on study through progression, up to 30 weeks, on average ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2016)
  • Area under the plasma concentration versus time curve (AUC) [ Time Frame: PK collected at multiple visits during the first 30 days of treatment ]
  • Peak Plasma Concentration (Cmax) [ Time Frame: PK collected at multiple visits during the first 30 days of treatment ]
  • Time of peak plasma concentration (TMax) [ Time Frame: 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) [ Time Frame: PK collected at multiple visits during the first 30 days of treatment ]
  • 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 ]
  • Rate of drug distribution within the blood stream (Vd/F) [ Time Frame: PK collected at multiple visits during the first 30 days of treatment ]
  • Observe patients for any evidence of anti-leukemic or anti-myelodysplastic activity of FT-2102 as single agent or in combination with azacitidine [ Time Frame: PK collected at multiple visits during the first 30 days of treatment ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: March 21, 2016)
  • Assessment of on-target activity of FT-2102, as determined by changes in a pharmacodynamic (PD) biomarker in plasma [ Time Frame: Assessed for duration of participation, an expected average of 12 weeks ]
  • To determine cancer-associated mutations and/or genetic alterations in responding and nonresponding patients [ Time Frame: Assessed for duration of participation, an expected average of 12 weeks ]
 
Descriptive Information
Brief Title  ICMJE Open-label Study of FT-2102 With or Without Azacitidine or Cytarabine in Patients With AML or MDS With an IDH1 Mutation
Official Title  ICMJE 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
Brief Summary This Phase 1/2 study will evaluate the safety, efficacy, PK, and PD of FT-2102 (olutasidenib) 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 (olutasidenib) (single agent) and FT-2102 (olutasidenib) + 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 (olutasidenib) 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 8 different cohorts, examining the effect of FT-2102 (olutasidenib) (as a single agent) and FT-2102 (olutasidenib) + azacitidine (combination) on various AML/MDS disease states.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myeloid Leukemia
  • Acute Myelogenous Leukemia
  • Myelodysplastic Syndrome
Intervention  ICMJE
  • Drug: FT-2102 (olutasidenib)
    FT-2102 (olutasidenib) will be supplied as 50 mg or 150 mg capsules and will be administered per the protocol defined frequency and dose level
  • Drug: Azacitidine
    azacitidine will be administered per site's standard of care
    Other Name: Vidaza
  • Drug: Cytarabine
    low-dose cytarabine will be administered per site's standard of care
Study Arms  ICMJE
  • Experimental: PH1 Dose Escalation & Expansion FT-2102 (olutasidenib)
    Intervention: Drug: FT-2102 (olutasidenib)
  • Experimental: PH1 Esc. and Exp. FT-2102 (olutasidenib)+Azacitidine
    Interventions:
    • Drug: FT-2102 (olutasidenib)
    • Drug: Azacitidine
  • Experimental: PH1 Esc. and Exp. FT-2102 (olutasidenib)+Cytarabine
    Interventions:
    • Drug: FT-2102 (olutasidenib)
    • Drug: Cytarabine
  • Experimental: PH2 Cohort 1 FT-2102 (olutasidenib) Single Agent
    Relapsed or Refractory (R/R) AML
    Intervention: Drug: FT-2102 (olutasidenib)
  • Experimental: PH2 Cohort 2 FT-2102 (olutasidenib) Single Agent
    AML in morphologic complete remission or complete remission with incomplete blood count recovery (CR/CRi) after prior therapy with residual IDH1-R132 mutation
    Intervention: Drug: FT-2102 (olutasidenib)
  • Experimental: PH2 Cohort 3 FT-2102 (olutasidenib) Single Agent
    R/R AML/MDS, previously treated with an IDH1 inhibitor
    Intervention: Drug: FT-2102 (olutasidenib)
  • Experimental: PH2 Cohort 4 FT-2102 (olutasidenib)+Azacitidine
    R/R AML/MDS that are naïve to prior hypomethylating therapy and IDH1 inhibitor therapy
    Interventions:
    • Drug: FT-2102 (olutasidenib)
    • Drug: Azacitidine
  • Experimental: PH2 Cohort 5 FT-2102 (olutasidenib)+Azacitidine
    R/R AML/MDS that have inadequately responded to or have progressed on prior hypomethylating therapy
    Interventions:
    • Drug: FT-2102 (olutasidenib)
    • Drug: Azacitidine
  • Experimental: PH2 Cohort 6 FT-2102 (olutasidenib)+Azacitidine
    R/R AML/MDS that have been previously treated with single-agent IDH1 inhibitor therapy as their last therapy prior to study enrollment
    Interventions:
    • Drug: FT-2102 (olutasidenib)
    • Drug: Azacitidine
  • Experimental: PH2 Cohort 7 FT-2102 (olutasidenib) Single Agent
    Treatment naïve AML for whom standard treatments are contraindicated
    Intervention: Drug: FT-2102 (olutasidenib)
  • Experimental: PH2 Cohort 8 FT-2102 (olutasidenib)+Azacitidine
    Treatment naïve AML who are candidates for azacitidine first line treatment
    Interventions:
    • Drug: FT-2102 (olutasidenib)
    • Drug: Azacitidine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 13, 2019)
500
Original Estimated Enrollment  ICMJE
 (submitted: March 21, 2016)
76
Estimated Study Completion Date  ICMJE September 2020
Estimated Primary Completion Date April 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Pathologically proven acute myeloid leukemia (AML) (except acute promyelocytic leukemia [APL] with the t(15;17) translocation) 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE Australia,   Canada,   France,   Germany,   Italy,   Korea, Republic of,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02719574
Other Study ID Numbers  ICMJE 2102-HEM-101
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Forma Therapeutics, Inc.
Study Sponsor  ICMJE Forma Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Forma Therapeutics, Inc.
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP