Clinical trial NCT02719574: Open-label Study of FT-2102 With or Without Azacitidine or Cytarabine in Patients With AML or MDS With an IDH1 Mutation
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia
Acute Myelogenous Leukemia
Myelodysplastic Syndrome
Keywords: AML
MDS
IDH1
IDH
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2016-03-25
Enrollment: 336
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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
* Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy

Primary outcomes:
measure: Maximum Tolerated Doses (MTDs) or Maximum Evaluated Doses (MEDs) [Phase 1]
timeFrame: Within first 4 weeks of treatment
measure: Number of Participants with a Dose Limiting Toxicity (DLT) [Phase 1]
timeFrame: Within first 4 weeks of treatment
measure: Doses recommended for future studies [Phase 1]
timeFrame: Within first 4 weeks of treatment
measure: 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]
timeFrame: 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
measure: 4-Month Relapse Free Survival (RFS) of FT-2102 (olutasidenib) single-agent [Phase 2 Cohort 2]
timeFrame: From time of entry on study through progression, up to 30 weeks, on average
Secondary outcomes:
measure: Area under the plasma concentration versus time curve (AUC) [Phase 1 and Phase 2]
timeFrame: 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
measure: Peak Plasma Concentration (Cmax) [Phase 1 and Phase 2]
timeFrame: 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
measure: Time of peak plasma concentration Tmax [Phase 1 and Phase 2]
timeFrame: 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
measure: Time for half of the drug to be absent in blood stream following dose (T 1/2) [Phase 1 and Phase 2]
timeFrame: 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
measure: Rate at which drug is removed from blood stream (CL/F) [Phase 1 and Phase 2]
timeFrame: 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
measure: Rate of drug distribution within the blood stream (Vd/F) [Phase 1 and Phase 2]
timeFrame: 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
measure: 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]
timeFrame: 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
measure: 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]
timeFrame: Safety will be assessed from time of first dose through 28 days post last dose.
measure: 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]
timeFrame: 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
measure: Time to Response (TTR) [Phase 2]
timeFrame: From first dose of study drug through time of first response by blood recovery count, up to 30 weeks, on average
measure: Duration of Response (DOR) [Phase 2]
timeFrame: From time of first response by blood recovery count through relapse, up to 30 weeks, on average
measure: Event-Free Survival (EFS) [Phase 2]
timeFrame: From time of entry on study through progression, up to 30 weeks, on average
measure: Overall Survival (OS) [Phase 2]
timeFrame: From time of entry on study through death or date last known alive at end of follow-up, up to 30 weeks, on average
measure: Relapse Free Survival (RFS) [Phase 2]
timeFrame: From time of entry on study through progression, up to 30 weeks, on average
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Cancer Center
state: Maryland
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Hawthorne
country: United States
facility: New York Medical College
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Cornell University Weill Medical College
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Nashville
country: United States
facility: Sarah Cannon Research Institute - Tennessee Oncology
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Parkville
country: Australia
facility: Victoria Cancer Care Center
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Box Hill
country: Australia
facility: Box Hill Hospital, Monash University and Eastern Health Clinical School
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Bobigny
country: France
facility: Service d'Hématologie Clinique, Hôpital Avicenne-APHP-Université Paris
city: Marseille
country: France
facility: Assistance Publique Hopitaux de Marseille (AP-HM) - Hopital Nord
city: Nantes
country: France
facility: Centre Hospitalier Universitaire Nantes
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Paris
country: France
facility: Hopitaux Universitaires Est Parisien Hopital Saint-Antoine
city: Pessac
country: France
facility: Centre Hospitalier Universitaire (CHU) Bordeaux - Hospitaux du Haut Leveque
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Rennes
country: France
facility: University Hospital of Rennes
city: Toulouse
country: France
facility: Institut Universitaire du Cancer Toulouse - Oncopole
city: Vandœuvre-lès-Nancy
country: France
facility: Centre Hospitalier Universitaire de Nancy - Hopital Brabois
city: Villejuif
country: France
facility: Institut de Cancérologie Gustave Roussy
city: Braunschweig
country: Germany
facility: Staedtisches Klinikum Braunschweig gGmbH
city: Gießen
country: Germany
facility: Universitaetsklinikum Giessen und Marburg GmbH - Klinik fuer Innere Medizin
city: Halle (Saale)
country: Germany
facility: Landeszentrum fuer Zell- und Gentherapie
city: Münster
country: Germany
facility: Universitätsklinikum Münster Medizinische Klinik A, Hämatologie, Hämostaseologi
city: Orbassano
country: Italy
facility: AOU S. Luigi Gonzaga - Orbassano
state: Turin
city: Ascoli Piceno
country: Italy
facility: Ospedale Mazzoni - UOC Ematologia Ascoli Piceno
city: Bologna
country: Italy
facility: Universita di Bologna
city: Meldola
country: Italy
facility: Dipartimento di Oncologia Medica - IRST IRCC
city: Parma
country: Italy
facility: Università degli Studi di Parma
city: Ravenna
country: Italy
facility: U.O. Ematologia Ravenna
city: Rimini
country: Italy
facility: Hospital Rimini Hematology, Department of Oncology and Hematoloy
city: Gumi
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Institut Català d'Oncologia-Hospital Duran i Reynals
city: Madrid
country: Spain
facility: Hospital Universitario 12 De Octubre
city: Salamanca
country: Spain
facility: Hospital Clínico Universitario de Salamanca
city: Valencia
country: Spain
facility: Hospital La Fe
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: St. George's University Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 2834)
role: STUDY_DIRECTOR
References:
citation: 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.