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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndrome; Acute Myelogenous Leukemia
• Intervention / Treatment: Drug: FT-2102 (olutasidenib); Drug: Azacitidine; Drug: Cytarabine

• Study Type: Interventional
• Enrollment (Actual): 336
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Box Hill, Australia, 3128
    • Box Hill Hospital, Monash University and Eastern Health Clinical School
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
    • Parkville, Victoria, Australia, 3000
      • Victoria Cancer Care Center
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
• France
  • Bobigny, France, 93000
    • Service d'Hématologie Clinique, Hôpital Avicenne-APHP-Université Paris
  • Marseille, France, 13005
    • Assistance Publique Hopitaux de Marseille (AP-HM) - Hopital Nord
  • Nantes, France, 44093
    • Centre Hospitalier Universitaire Nantes
  • Paris, France, 75010
    • Hôpital Saint-Louis
  • Paris, France, 75012
    • Hopitaux Universitaires Est Parisien Hopital Saint-Antoine
  • Pessac, France, 33604
    • Centre Hospitalier Universitaire (CHU) Bordeaux - Hospitaux du Haut Leveque
  • Pierre-Bénite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Rennes, France, 35033
    • University Hospital of Rennes
  • Toulouse, France, 31059
    • Institut Universitaire du Cancer Toulouse - Oncopole
  • Vandœuvre-lès-Nancy, France, 54511
    • Centre Hospitalier Universitaire de Nancy - Hopital Brabois
  • Villejuif, France, 94805
    • Institut de Cancerologie Gustave Roussy
• Germany
  • Braunschweig, Germany
    • Staedtisches Klinikum Braunschweig gGmbH
  • Gießen, Germany
    • Universitaetsklinikum Giessen und Marburg GmbH - Klinik fuer Innere Medizin
  • Halle (Saale), Germany
    • Landeszentrum fuer Zell- und Gentherapie
  • Münster, Germany
    • Universitätsklinikum Münster Medizinische Klinik A, Hämatologie, Hämostaseologi
• Italy
  • Ascoli Piceno, Italy
    • Ospedale Mazzoni - UOC Ematologia Ascoli Piceno
  • Bologna, Italy
    • Universita di Bologna
  • Meldola, Italy
    • Dipartimento di Oncologia Medica - IRST IRCC
  • Parma, Italy
    • Università degli Studi di Parma
  • Ravenna, Italy
    • U.O. Ematologia Ravenna
  • Rimini, Italy
    • Hospital Rimini Hematology, Department of Oncology and Hematoloy
  • Turin
    • Orbassano, Turin, Italy
      • AOU S. Luigi Gonzaga - Orbassano
• Korea, Republic of
  • Gumi, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Barcelona, Spain, 8036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 8908
    • Institut Català d'Oncologia-Hospital Duran i Reynals
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Salamanca, Spain, 37007
    • Hospital Clínico Universitario de Salamanca
  • Valencia, Spain, 46026
    • Hospital La Fe
• United Kingdom
  • London, United Kingdom, NW1 2PG
    • University College London Hospitals NHS Foundation Trust
  • London, United Kingdom
    • St. George's University Hospital
  • Oxford, United Kingdom
    • Churchill Hospital
  • Southampton, United Kingdom
    • Southampton General Hospital
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital
• United States
  • California
    • Los Angeles, California, United States, 90024
      • UCLA Medical Center
    • Sacramento, California, United States, 95817
      • UC Davis Comprehensive Cancer Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Winship Cancer Institute
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Greenebaum Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Hawthorne, New York, United States, 10532
      • New York Medical College
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Cornell University Weill Medical College
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97229
      • Oregon Health & Science University
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute - Tennessee Oncology
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

11

Arms and Interventions

Participant Group / 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 Names: 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 FT-2102	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 Names: 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 Names: Vidaza
Experimental: 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	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 Names: 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 Names: Vidaza

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Tolerated Doses (MTDs) or Maximum Evaluated Doses (MEDs) [Phase 1]	Within first 4 weeks of treatment
Number of Participants with a Dose Limiting Toxicity (DLT) [Phase 1]	Within first 4 weeks of treatment
Doses recommended for future studies [Phase 1]	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]	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]	From time of entry on study through progression, up to 30 weeks, on average

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under the plasma concentration versus time curve (AUC) [Phase 1 and Phase 2]	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]	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]	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]	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]	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]	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]	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]	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]	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]	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]	From time of first response by blood recovery count through relapse, up to 30 weeks, on average
Event-Free Survival (EFS) [Phase 2]	From time of entry on study through progression, up to 30 weeks, on average
Overall Survival (OS) [Phase 2]	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]	From time of entry on study through progression, up to 30 weeks, on average

Collaborators and Investigators

• Sponsor: Forma Therapeutics, Inc.
• Investigators: Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S

Publications and helpful links

General Publications

• 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. Erratum In: Lancet Haematol. 2023 Jan;10(1):e9.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): December 28, 2023
• Study Completion (Actual): January 24, 2024

Study Registration Dates

• First Submitted: March 21, 2016
• First Submitted That Met QC Criteria: March 21, 2016
• First Posted (Estimated): March 25, 2016

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: AML; MDS; IDH; IDH1
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Azacitidine; Cytarabine
• Other Study ID Numbers: 2102-HEM-101