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

Sponsor

Forma Therapeutics, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02719574

Collaborator

(none)

336

Enrollment

Locations

Arms

Anticipated Duration (Months)

5.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Acute Myelogenous Leukemia Myelodysplastic Syndrome	Drug: FT-2102 (olutasidenib) Drug: Azacitidine Drug: Cytarabine	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

336 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 1, 2016

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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