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

Phase 1

Completed

• Conditions: Acute Myelogenous Leukemia; Myelodysplastic Syndrome; Acute Myeloid Leukemia
• Interventions: Drug: FT-2102 (olutasidenib); Drug: Azacitidine; Drug: Cytarabine

• Registration Number: NCT02719574
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-03-21
• Study First Submitted QC: 2016-03-21
• Study First Posted: 2016-03-25
• Study Start: 2016-04
• Primary Completion: 2023-12-28
• Study Completion: 2024-01-24
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-04
• Last Update Posted: 2024-11-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 336

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PH1 Dose Escalation & Expansion FT-2102 (olutasidenib)	FT-2102 (olutasidenib)	-
PH2 Cohort 6 FT-2102 (olutasidenib)+Azacitidine	FT-2102 (olutasidenib)	R/R AML/MDS that have been previously treated with single-agent FT-2102 as their last therapy prior to study enrollment
PH1 Esc. and Exp. FT-2102 (olutasidenib)+Azacitidine	FT-2102 (olutasidenib)	-
PH1 Esc. and Exp. FT-2102 (olutasidenib)+Cytarabine	FT-2102 (olutasidenib)	-
PH2 Cohort 1 FT-2102 (olutasidenib) Single Agent	FT-2102 (olutasidenib)	Relapsed or Refractory (R/R) AML
PH2 Cohort 2 FT-2102 (olutasidenib) Single Agent	FT-2102 (olutasidenib)	AML in morphologic complete remission or complete remission with incomplete blood count recovery (CR/CRi) after prior therapy with residual IDH1-R132 mutation
PH2 Cohort 3 FT-2102 (olutasidenib) Single Agent	FT-2102 (olutasidenib)	R/R AML/MDS, previously treated with FT-2102
PH2 Cohort 4 FT-2102 (olutasidenib)+Azacitidine	FT-2102 (olutasidenib)	R/R AML/MDS that are naïve to prior hypomethylating therapy and IDH1 inhibitor therapy
PH2 Cohort 5 FT-2102 (olutasidenib)+Azacitidine	FT-2102 (olutasidenib)	R/R AML/MDS that have inadequately responded to or have progressed on prior hypomethylating therapy
PH2 Cohort 7 FT-2102 (olutasidenib) Single Agent	FT-2102 (olutasidenib)	Treatment naïve AML for whom standard treatments are contraindicated
PH2 Cohort 8 FT-2102 (olutasidenib)+Azacitidine	FT-2102 (olutasidenib)	Treatment naïve AML who are candidates for azacitidine first line treatment
PH1 Esc. and Exp. FT-2102 (olutasidenib)+Azacitidine	Azacitidine	-
PH1 Esc. and Exp. FT-2102 (olutasidenib)+Cytarabine	Cytarabine	-
PH2 Cohort 4 FT-2102 (olutasidenib)+Azacitidine	Azacitidine	R/R AML/MDS that are naïve to prior hypomethylating therapy and IDH1 inhibitor therapy
PH2 Cohort 6 FT-2102 (olutasidenib)+Azacitidine	Azacitidine	R/R AML/MDS that have been previously treated with single-agent FT-2102 as their last therapy prior to study enrollment
PH2 Cohort 5 FT-2102 (olutasidenib)+Azacitidine	Azacitidine	R/R AML/MDS that have inadequately responded to or have progressed on prior hypomethylating therapy
PH2 Cohort 8 FT-2102 (olutasidenib)+Azacitidine	Azacitidine	Treatment naïve AML who are candidates for azacitidine first line treatment

Primary Outcome Measures

Name	Time	Method
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
Maximum Tolerated Doses (MTDs) or Maximum Evaluated Doses (MEDs) [Phase 1]	Within first 4 weeks of treatment
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

Name	Time	Method
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
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
Duration of Response (DOR) [Phase 2]	From time of first response by blood recovery count through relapse, 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
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
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
Event-Free Survival (EFS) [Phase 2]	From time of entry on study through progression, 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

Trial Locations

Locations (60)

UCLA Medical Center; 🇺🇸 Los Angeles, California, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Box Hill Hospital, Monash University and Eastern Health Clinical School; 🇦🇺 Box Hill, Australia

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States

Emory Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

New York Medical College; 🇺🇸 Hawthorne, New York, United States

The Alfred Hospital; 🇦🇺 Melbourne, Victoria, Australia

Sir Charles Gairdner Hospital; 🇦🇺 Nedlands, Western Australia, Australia

Landeszentrum fuer Zell- und Gentherapie; 🇩🇪 Halle (Saale), Germany

Institut Universitaire du Cancer Toulouse - Oncopole; 🇫🇷 Toulouse, France

AOU S. Luigi Gonzaga - Orbassano; 🇮🇹 Orbassano, Turin, Italy

Seoul National University Bundang Hospital; 🇰🇷 Gumi, Korea, Republic of

U.O. Ematologia Ravenna; 🇮🇹 Ravenna, Italy

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Hospital Clínico Universitario de Salamanca; 🇪🇸 Salamanca, Spain

Southampton General Hospital; 🇬🇧 Southampton, United Kingdom

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

UC Davis Comprehensive Cancer Center; 🇺🇸 Sacramento, California, United States

Assistance Publique Hopitaux de Marseille (AP-HM) - Hopital Nord; 🇫🇷 Marseille, France

The Ohio State University; 🇺🇸 Columbus, Ohio, United States

Victoria Cancer Care Center; 🇦🇺 Parkville, Victoria, Australia

Staedtisches Klinikum Braunschweig gGmbH; 🇩🇪 Braunschweig, Germany

University of Maryland Greenebaum Cancer Center; 🇺🇸 Baltimore, Maryland, United States

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

Princess Margaret Hospital; 🇨🇦 Toronto, Ontario, Canada

University College London Hospitals NHS Foundation Trust; 🇬🇧 London, United Kingdom

Hospital Universitario 12 De Octubre; 🇪🇸 Madrid, Spain

Centre Hospitalier Universitaire Nantes; 🇫🇷 Nantes, France

Universitaetsklinikum Giessen und Marburg GmbH - Klinik fuer Innere Medizin; 🇩🇪 Gießen, Germany

Institut Català d'Oncologia-Hospital Duran i Reynals; 🇪🇸 Barcelona, Spain

Hospital La Fe; 🇪🇸 Valencia, Spain

Churchill Hospital; 🇬🇧 Oxford, United Kingdom

Ospedale Mazzoni - UOC Ematologia Ascoli Piceno; 🇮🇹 Ascoli Piceno, Italy

Universita di Bologna; 🇮🇹 Bologna, Italy

Dipartimento di Oncologia Medica - IRST IRCC; 🇮🇹 Meldola, Italy

University of Miami; 🇺🇸 Miami, Florida, United States

Northwestern University Feinberg School of Medicine; 🇺🇸 Chicago, Illinois, United States

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Sarah Cannon Research Institute - Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Service d'Hématologie Clinique, Hôpital Avicenne-APHP-Université Paris; 🇫🇷 Bobigny, France

Hôpital Saint-Louis; 🇫🇷 Paris, France

Centre Hospitalier Universitaire (CHU) Bordeaux - Hospitaux du Haut Leveque; 🇫🇷 Pessac, France

Centre Hospitalier Lyon Sud; 🇫🇷 Pierre-Bénite, France

Centre Hospitalier Universitaire de Nancy - Hopital Brabois; 🇫🇷 Vandœuvre-lès-Nancy, France

Institut de Cancérologie Gustave Roussy; 🇫🇷 Villejuif, France

University Hospital of Rennes; 🇫🇷 Rennes, France

Royal Marsden Hospital; 🇬🇧 Sutton, United Kingdom

Universitätsklinikum Münster Medizinische Klinik A, Hämatologie, Hämostaseologi; 🇩🇪 Münster, Germany

Cornell University Weill Medical College; 🇺🇸 New York, New York, United States

St. George's University Hospital; 🇬🇧 London, United Kingdom

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Hopitaux Universitaires Est Parisien Hopital Saint-Antoine; 🇫🇷 Paris, France

Università degli Studi di Parma; 🇮🇹 Parma, Italy

Hospital Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Clinic de Barcelona; 🇪🇸 Barcelona, Spain

Hospital Rimini Hematology, Department of Oncology and Hematoloy; 🇮🇹 Rimini, Italy