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

NCT ID: NCT02719574

Last Updated: 2025-06-26

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

336 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-04-30

Study Completion Date

2024-01-24

Brief Summary

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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

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Conditions

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Acute Myeloid Leukemia Acute Myelogenous Leukemia Myelodysplastic Syndrome

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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PH1 Dose Escalation & Expansion FT-2102 (olutasidenib)

Group Type EXPERIMENTAL

FT-2102 (olutasidenib)

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

FT-2102 (olutasidenib)

Intervention Type DRUG

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

Azacitidine

Intervention Type DRUG

azacitidine will be administered per site's standard of care

PH1 Esc. and Exp. FT-2102 (olutasidenib)+Cytarabine

Group Type EXPERIMENTAL

FT-2102 (olutasidenib)

Intervention Type DRUG

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

Cytarabine

Intervention Type DRUG

low-dose cytarabine will be administered per site's standard of care

PH2 Cohort 1 FT-2102 (olutasidenib) Single Agent

Relapsed or Refractory (R/R) AML

Group Type EXPERIMENTAL

FT-2102 (olutasidenib)

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

FT-2102 (olutasidenib)

Intervention Type DRUG

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

PH2 Cohort 3 FT-2102 (olutasidenib) Single Agent

R/R AML/MDS, previously treated with FT-2102

Group Type EXPERIMENTAL

FT-2102 (olutasidenib)

Intervention Type DRUG

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

PH2 Cohort 4 FT-2102 (olutasidenib)+Azacitidine

R/R AML/MDS that are naïve to prior hypomethylating therapy and IDH1 inhibitor therapy

Group Type EXPERIMENTAL

FT-2102 (olutasidenib)

Intervention Type DRUG

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

Azacitidine

Intervention Type DRUG

azacitidine will be administered per site's standard of care

PH2 Cohort 5 FT-2102 (olutasidenib)+Azacitidine

R/R AML/MDS that have inadequately responded to or have progressed on prior hypomethylating therapy

Group Type EXPERIMENTAL

FT-2102 (olutasidenib)

Intervention Type DRUG

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

Azacitidine

Intervention Type DRUG

azacitidine will be administered per site's standard of care

PH2 Cohort 6 FT-2102 (olutasidenib)+Azacitidine

R/R AML/MDS that have been previously treated with single-agent FT-2102 as their last therapy prior to study enrollment

Group Type EXPERIMENTAL

FT-2102 (olutasidenib)

Intervention Type DRUG

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

Azacitidine

Intervention Type DRUG

azacitidine will be administered per site's standard of care

PH2 Cohort 7 FT-2102 (olutasidenib) Single Agent

Treatment naïve AML for whom standard treatments are contraindicated

Group Type EXPERIMENTAL

FT-2102 (olutasidenib)

Intervention Type DRUG

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

PH2 Cohort 8 FT-2102 (olutasidenib)+Azacitidine

Treatment naïve AML who are candidates for azacitidine first line treatment

Group Type EXPERIMENTAL

FT-2102 (olutasidenib)

Intervention Type DRUG

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

Azacitidine

Intervention Type DRUG

azacitidine will be administered per site's standard of care

Interventions

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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

Intervention Type DRUG

Azacitidine

azacitidine will be administered per site's standard of care

Intervention Type DRUG

Cytarabine

low-dose cytarabine will be administered per site's standard of care

Intervention Type DRUG

Other Intervention Names

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Vidaza

Eligibility Criteria

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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
* Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Forma Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Transparency (dept. 2834)

Role: STUDY_DIRECTOR

Novo Nordisk A/S

Locations

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UCLA Medical Center

Los Angeles, California, United States

Site Status

UC Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

Emory Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

Site Status

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, United States

Site Status

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

New York Medical College

Hawthorne, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Cornell University Weill Medical College

New York, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

The Ohio State University

Columbus, Ohio, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

Sarah Cannon Research Institute - Tennessee Oncology

Nashville, Tennessee, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

The Alfred Hospital

Melbourne, Victoria, Australia

Site Status

Victoria Cancer Care Center

Parkville, Victoria, Australia

Site Status

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Site Status

Box Hill Hospital, Monash University and Eastern Health Clinical School

Box Hill, , Australia

Site Status

Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

Service d'Hématologie Clinique, Hôpital Avicenne-APHP-Université Paris

Bobigny, , France

Site Status

Assistance Publique Hopitaux de Marseille (AP-HM) - Hopital Nord

Marseille, , France

Site Status

Centre Hospitalier Universitaire Nantes

Nantes, , France

Site Status

Hôpital Saint-Louis

Paris, , France

Site Status

Hopitaux Universitaires Est Parisien Hopital Saint-Antoine

Paris, , France

Site Status

Centre Hospitalier Universitaire (CHU) Bordeaux - Hospitaux du Haut Leveque

Pessac, , France

Site Status

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Site Status

University Hospital of Rennes

Rennes, , France

Site Status

Institut Universitaire du Cancer Toulouse - Oncopole

Toulouse, , France

Site Status

Centre Hospitalier Universitaire de Nancy - Hopital Brabois

Vandœuvre-lès-Nancy, , France

Site Status

Institut de Cancérologie Gustave Roussy

Villejuif, , France

Site Status

Staedtisches Klinikum Braunschweig gGmbH

Braunschweig, , Germany

Site Status

Universitaetsklinikum Giessen und Marburg GmbH - Klinik fuer Innere Medizin

Giessen, , Germany

Site Status

Landeszentrum fuer Zell- und Gentherapie

Halle, , Germany

Site Status

Universitätsklinikum Münster Medizinische Klinik A, Hämatologie, Hämostaseologi

Münster, , Germany

Site Status

AOU S. Luigi Gonzaga - Orbassano

Orbassano, Turin, Italy

Site Status

Ospedale Mazzoni - UOC Ematologia Ascoli Piceno

Ascoli Piceno, , Italy

Site Status

Universita di Bologna

Bologna, , Italy

Site Status

Dipartimento di Oncologia Medica - IRST IRCC

Meldola, , Italy

Site Status

Università degli Studi di Parma

Parma, , Italy

Site Status

U.O. Ematologia Ravenna

Ravenna, , Italy

Site Status

Hospital Rimini Hematology, Department of Oncology and Hematoloy

Rimini, , Italy

Site Status

Seoul National University Bundang Hospital

Gumi, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Hospital Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status

Institut Català d'Oncologia-Hospital Duran i Reynals

Barcelona, , Spain

Site Status

Hospital Universitario 12 De Octubre

Madrid, , Spain

Site Status

Hospital Clínico Universitario de Salamanca

Salamanca, , Spain

Site Status

Hospital La Fe

Valencia, , Spain

Site Status

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status

St. George's University Hospital

London, , United Kingdom

Site Status

Churchill Hospital

Oxford, , United Kingdom

Site Status

Southampton General Hospital

Southampton, , United Kingdom

Site Status

Royal Marsden Hospital

Sutton, , United Kingdom

Site Status

Countries

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United States Australia Canada France Germany Italy South Korea Spain United Kingdom

References

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Cortes JE, Yang J, Roboz GJ, Dinner SN, Wang ES, Wei AH, Tian H, di Trapani F, Baer MR, Donnellan WB, Watts JM. Olutasidenib alone or combined with azacitidine in patients with mutant IDH1 myelodysplastic syndrome. Blood Adv. 2025 Jul 16:bloodadvances.2025016718. doi: 10.1182/bloodadvances.2025016718. Online ahead of print.

Reference Type DERIVED
PMID: 40668616 (View on PubMed)

Cortes JE, Roboz GJ, Baer MR, Jonas BA, Schiller GJ, Yee K, Ferrell PB, Yang J, Wang ES, Blum WG, Mims A, Tian H, Sheppard A, de Botton S, Montesinos P, Curti A, Watts JM; Olutasidenib Combination Therapy Study Group. Olutasidenib in combination with azacitidine induces durable complete remissions in patients with relapsed or refractory mIDH1 acute myeloid leukemia: a multicohort open-label phase 1/2 trial. J Hematol Oncol. 2025 Jan 16;18(1):7. doi: 10.1186/s13045-024-01657-z.

Reference Type DERIVED
PMID: 39819505 (View on PubMed)

de Botton S, Fenaux P, Yee K, Recher C, Wei AH, Montesinos P, Taussig DC, Pigneux A, Braun T, Curti A, Grove C, Jonas BA, Khwaja A, Legrand O, Peterlin P, Arnan M, Blum W, Cilloni D, Hiwase DK, Jurcic JG, Krauter J, Thomas X, Watts JM, Yang J, Polyanskaya O, Brevard J, Sweeney J, Barrett E, Cortes J. Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed or refractory IDH1-mutated AML. Blood Adv. 2023 Jul 11;7(13):3117-3127. doi: 10.1182/bloodadvances.2022009411.

Reference Type DERIVED
PMID: 36724515 (View on PubMed)

Watts JM, Baer MR, Yang J, Prebet T, Lee S, Schiller GJ, Dinner SN, Pigneux A, Montesinos P, Wang ES, Seiter KP, Wei AH, De Botton S, Arnan M, Donnellan W, Schwarer AP, Recher C, Jonas BA, Ferrell PB Jr, Marzac C, Kelly P, Sweeney J, Forsyth S, Guichard SM, Brevard J, Henrick P, Mohamed H, Cortes JE. Olutasidenib alone or with azacitidine in IDH1-mutated acute myeloid leukaemia and myelodysplastic syndrome: phase 1 results of a phase 1/2 trial. Lancet Haematol. 2023 Jan;10(1):e46-e58. doi: 10.1016/S2352-3026(22)00292-7. Epub 2022 Nov 10.

Reference Type DERIVED
PMID: 36370742 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2102-HEM-101

Identifier Type: -

Identifier Source: org_study_id

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