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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.

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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Acute Myelogenous Leukemia Myelodysplastic Syndrome Drug: FT-2102 (olutasidenib) Drug: Azacitidine Drug: Cytarabine Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : April 2016
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : September 2020


Arm Intervention/treatment
Experimental: PH1 Dose Escalation & Expansion FT-2102 (olutasidenib) 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

Experimental: PH1 Esc. and Exp. FT-2102 (olutasidenib)+Azacitidine 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

Experimental: PH1 Esc. and Exp. FT-2102 (olutasidenib)+Cytarabine 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: Cytarabine
low-dose cytarabine will be administered per site's standard of care

Experimental: PH2 Cohort 1 FT-2102 (olutasidenib) Single Agent
Relapsed or Refractory (R/R) AML
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

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
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

Experimental: PH2 Cohort 3 FT-2102 (olutasidenib) Single Agent
R/R AML/MDS, previously treated with an IDH1 inhibitor
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

Experimental: PH2 Cohort 4 FT-2102 (olutasidenib)+Azacitidine
R/R AML/MDS that are naïve to prior hypomethylating therapy and IDH1 inhibitor therapy
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

Experimental: PH2 Cohort 5 FT-2102 (olutasidenib)+Azacitidine
R/R AML/MDS that have inadequately responded to or have progressed on prior hypomethylating therapy
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

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
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

Experimental: PH2 Cohort 7 FT-2102 (olutasidenib) Single Agent
Treatment naïve AML for whom standard treatments are contraindicated
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

Experimental: PH2 Cohort 8 FT-2102 (olutasidenib)+Azacitidine
Treatment naïve AML who are candidates for azacitidine first line treatment
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




Primary Outcome Measures :
  1. Maximum Tolerated Doses (MTDs) or Maximum Evaluated Doses (MEDs) [Phase 1] [ Time Frame: Within first 4 weeks of treatment ]
  2. Number of Participants with a Dose Limiting Toxicity (DLT) [Phase 1] [ Time Frame: Within first 4 weeks of treatment ]
  3. Doses recommended for future studies [Phase 1] [ Time Frame: Within first 4 weeks of treatment ]
  4. 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 ]
  5. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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. ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. Event-Free Survival (EFS) [Phase 2] [ Time Frame: From time of entry on study through progression, up to 30 weeks, on average ]
  13. 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 ]
  14. Relapse Free Survival (RFS) [Phase 2] [ Time Frame: From time of entry on study through progression, up to 30 weeks, on average ]


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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

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

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): NCT02719574


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Sponsors and Collaborators
Forma Therapeutics, Inc.

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Responsible Party: Forma Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02719574     History of Changes
Other Study ID Numbers: 2102-HEM-101
First Posted: March 25, 2016    Key Record Dates
Last Update Posted: December 5, 2019
Last Verified: December 2019
Keywords provided by Forma Therapeutics, Inc.:
AML
MDS
IDH1
IDH
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Cytarabine
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors