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

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02719574
• Other study ID #: 2102-HEM-101
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 2016
• Est. completion date: January 24, 2024

Study information

• Verified date: April 2024
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 336
• Est. completion date: January 24, 2024
• Est. primary completion date: December 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myelogenous Leukemia
• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia

Intervention

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
• Azacitidine
azacitidine will be administered per site's standard of care
• Cytarabine
low-dose cytarabine will be administered per site's standard of care

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Forma Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Italy,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Doses (MTDs) or Maximum Evaluated Doses (MEDs) [Phase 1]		Within first 4 weeks of treatment
Primary	Number of Participants with a Dose Limiting Toxicity (DLT) [Phase 1]		Within first 4 weeks of treatment
Primary	Doses recommended for future studies [Phase 1]		Within first 4 weeks of treatment
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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.
Secondary	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
Secondary	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
Secondary	Duration of Response (DOR) [Phase 2]		From time of first response by blood recovery count through relapse, up to 30 weeks, on average
Secondary	Event-Free Survival (EFS) [Phase 2]		From time of entry on study through progression, up to 30 weeks, on average
Secondary	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
Secondary	Relapse Free Survival (RFS) [Phase 2]		From time of entry on study through progression, up to 30 weeks, on average