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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02719574




Registration number
NCT02719574
Ethics application status
Date submitted
21/03/2016
Date registered
25/03/2016
Date last updated
10/04/2024

Titles & IDs
Public title
Open-label Study of FT-2102 With or Without Azacitidine or Cytarabine in Patients With AML or MDS With an IDH1 Mutation
Scientific 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
Secondary ID [1] 0 0
2102-HEM-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia 0 0
Acute Myelogenous Leukemia 0 0
Myelodysplastic Syndrome 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - FT-2102 (olutasidenib)
Treatment: Drugs - Azacitidine
Treatment: Drugs - Cytarabine

Experimental: PH1 Dose Escalation & Expansion FT-2102 (olutasidenib) -

Experimental: PH1 Esc. and Exp. FT-2102 (olutasidenib)+Azacitidine -

Experimental: PH1 Esc. and Exp. FT-2102 (olutasidenib)+Cytarabine -

Experimental: PH2 Cohort 1 FT-2102 (olutasidenib) Single Agent - Relapsed or Refractory (R/R) AML

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

Experimental: PH2 Cohort 3 FT-2102 (olutasidenib) Single Agent - R/R AML/MDS, previously treated with FT-2102

Experimental: PH2 Cohort 4 FT-2102 (olutasidenib)+Azacitidine - R/R AML/MDS that are naïve to prior hypomethylating therapy and IDH1 inhibitor therapy

Experimental: PH2 Cohort 5 FT-2102 (olutasidenib)+Azacitidine - R/R AML/MDS that have inadequately responded to or have progressed on prior hypomethylating therapy

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

Experimental: PH2 Cohort 7 FT-2102 (olutasidenib) Single Agent - Treatment naïve AML for whom standard treatments are contraindicated

Experimental: PH2 Cohort 8 FT-2102 (olutasidenib)+Azacitidine - Treatment naïve AML who are candidates for azacitidine first line treatment


Treatment: Drugs: 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

Treatment: Drugs: Azacitidine
azacitidine will be administered per site's standard of care

Treatment: Drugs: Cytarabine
low-dose cytarabine will be administered per site's standard of care
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum Tolerated Doses (MTDs) or Maximum Evaluated Doses (MEDs) [Phase 1]
Timepoint [1] 0 0
Within first 4 weeks of treatment
Primary outcome [2] 0 0
Number of Participants with a Dose Limiting Toxicity (DLT) [Phase 1]
Timepoint [2] 0 0
Within first 4 weeks of treatment
Primary outcome [3] 0 0
Doses recommended for future studies [Phase 1]
Timepoint [3] 0 0
Within first 4 weeks of treatment
Primary outcome [4] 0 0
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]
Timepoint [4] 0 0
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 outcome [5] 0 0
4-Month Relapse Free Survival (RFS) of FT-2102 (olutasidenib) single-agent [Phase 2 Cohort 2]
Timepoint [5] 0 0
From time of entry on study through progression, up to 30 weeks, on average
Secondary outcome [1] 0 0
Area under the plasma concentration versus time curve (AUC) [Phase 1 and Phase 2]
Timepoint [1] 0 0
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 outcome [2] 0 0
Peak Plasma Concentration (Cmax) [Phase 1 and Phase 2]
Timepoint [2] 0 0
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 outcome [3] 0 0
Time of peak plasma concentration Tmax [Phase 1 and Phase 2]
Timepoint [3] 0 0
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 outcome [4] 0 0
Time for half of the drug to be absent in blood stream following dose (T 1/2) [Phase 1 and Phase 2]
Timepoint [4] 0 0
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 outcome [5] 0 0
Rate at which drug is removed from blood stream (CL/F) [Phase 1 and Phase 2]
Timepoint [5] 0 0
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 outcome [6] 0 0
Rate of drug distribution within the blood stream (Vd/F) [Phase 1 and Phase 2]
Timepoint [6] 0 0
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 outcome [7] 0 0
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]
Timepoint [7] 0 0
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 outcome [8] 0 0
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]
Timepoint [8] 0 0
Safety will be assessed from time of first dose through 28 days post last dose.
Secondary outcome [9] 0 0
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]
Timepoint [9] 0 0
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 outcome [10] 0 0
Time to Response (TTR) [Phase 2]
Timepoint [10] 0 0
From first dose of study drug through time of first response by blood recovery count, up to 30 weeks, on average
Secondary outcome [11] 0 0
Duration of Response (DOR) [Phase 2]
Timepoint [11] 0 0
From time of first response by blood recovery count through relapse, up to 30 weeks, on average
Secondary outcome [12] 0 0
Event-Free Survival (EFS) [Phase 2]
Timepoint [12] 0 0
From time of entry on study through progression, up to 30 weeks, on average
Secondary outcome [13] 0 0
Overall Survival (OS) [Phase 2]
Timepoint [13] 0 0
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 outcome [14] 0 0
Relapse Free Survival (RFS) [Phase 2]
Timepoint [14] 0 0
From time of entry on study through progression, up to 30 weeks, on average

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/04/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/01/2024
Sample size
Target
Accrual to date
Final
336
Recruitment in Australia
Recruitment state(s)
SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [3] 0 0
Victoria Cancer Care Center - Parkville
Recruitment hospital [4] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [5] 0 0
Box Hill Hospital, Monash University and Eastern Health Clinical School - Box Hill
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
3000 - Parkville
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment postcode(s) [5] 0 0
3128 - Box Hill
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Oregon
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
Canada
State/province [14] 0 0
Ontario
Country [15] 0 0
France
State/province [15] 0 0
Bobigny
Country [16] 0 0
France
State/province [16] 0 0
Marseille
Country [17] 0 0
France
State/province [17] 0 0
Nantes
Country [18] 0 0
France
State/province [18] 0 0
Paris
Country [19] 0 0
France
State/province [19] 0 0
Pessac
Country [20] 0 0
France
State/province [20] 0 0
Pierre-Bénite
Country [21] 0 0
France
State/province [21] 0 0
Rennes
Country [22] 0 0
France
State/province [22] 0 0
Toulouse
Country [23] 0 0
France
State/province [23] 0 0
Vandœuvre-lès-Nancy
Country [24] 0 0
France
State/province [24] 0 0
Villejuif
Country [25] 0 0
Germany
State/province [25] 0 0
Braunschweig
Country [26] 0 0
Germany
State/province [26] 0 0
Gießen
Country [27] 0 0
Germany
State/province [27] 0 0
Halle (Saale)
Country [28] 0 0
Germany
State/province [28] 0 0
Münster
Country [29] 0 0
Italy
State/province [29] 0 0
Turin
Country [30] 0 0
Italy
State/province [30] 0 0
Ascoli Piceno
Country [31] 0 0
Italy
State/province [31] 0 0
Bologna
Country [32] 0 0
Italy
State/province [32] 0 0
Meldola
Country [33] 0 0
Italy
State/province [33] 0 0
Parma
Country [34] 0 0
Italy
State/province [34] 0 0
Ravenna
Country [35] 0 0
Italy
State/province [35] 0 0
Rimini
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Gumi
Country [37] 0 0
Korea, Republic of
State/province [37] 0 0
Seoul
Country [38] 0 0
Spain
State/province [38] 0 0
Barcelona
Country [39] 0 0
Spain
State/province [39] 0 0
Madrid
Country [40] 0 0
Spain
State/province [40] 0 0
Salamanca
Country [41] 0 0
Spain
State/province [41] 0 0
Valencia
Country [42] 0 0
United Kingdom
State/province [42] 0 0
London
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Oxford
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Southampton
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Forma Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02719574
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Transparency (dept. 2834)
Address 0 0
Novo Nordisk A/S
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02719574