A Phase 3 Multicenter, Open-label, Randomized Study of ASP2215 (Gilteritinib), Combination of ASP2215 Plus Azacitidine and Azacitidine Alone in the Treatment of Newly Diagnosed Acute Myeloid Leukemia with FLT3 Mutation in Patients Not Eligible for Intensive Induction Chemotherapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Astellas Pharma Global Development Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

7 Nov 2016 → 18 Dec 2024

Decision date (initial)

2024-06-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Astellas Pharma Global Development Inc.

External identifiers

EU CT number

2024-512474-98-00

EudraCT number

2015-001790-41

ClinicalTrials.gov

NCT02752035

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Pharmacogenomic, Therapy, Efficacy, Pharmacodynamic

The primary objective is to determine the efficacy superiority of ASP2215 plus azacitidine versus azacitidine as measured by overal survival (OS).

Secondary objectives 2

1. The key secondary objective is to determine the efficacy superiority of ASP2215 plus azacitidine versus azacitidine as measured by event-free survival (EFS)
2. The additional secondary objectives are to evaluate the safety and efficacy of ASP2215 plus azacitidine versus azacitidine in terms of: ● Best response, ● Complete remission (CR) rate, ● CRc rate, ●,CRh rate, ● CR/CRh rate, ● Transfusion conversion rate; transfusion maintenance rate, ● Leukemia-free survival (LFS), ● Duration of remission, ● Patient-reported fatigue (Brief Fatigue Inventory [BFI]), ● Adverse events (AEs), clinical laboratory results, physical examinations, vital signs, ECGs) and Eastern Cooperative Oncology Group (ECOG) performance scores

Conditions and MedDRA coding

Newly Diagnosed Acute Myeloid Leukemia with FLT3 Mutation in Patients Not Eligible for Intensive Induction Chemotherapy

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. 3. Subject has a diagnosis of previously-untreated AML according to World Health Organization (WHO) classification [Swerdlow et al, 2008] as determined by pathology review at the treating institution.
2. 4. Subject is positive for FLT3 mutation (ITD or TKD [D835/I836] mutation). NOTE: Requirement of FLT3 mutation assessment by central laboratory is only applicable to the randomization portion of the study.
3. 5. Subject is ineligible for intensive induction chemotherapy by meeting at least 1 of the following criteria: a. Subject is ≥ 65 years of age and ineligible for intensive induction chemotherapy per investigator’s discretion. b. Subject is ≥ 18 to 64 years of age and has any of the following comorbidities: i. Congestive heart failure (New York Heart Association (NYHA) class ≤ 3) or ejection fraction (EF) ≤ 50%; ii. Creatinine > 2 mg/dL (177 µmol/L), dialysis or prior renal transplant; iii. ECOG performance status ≥ 2; iv. Prior or current malignancy that does not require concurrent treatment; v. Subject has received a cumulative anthracycline dose above 400 mg/m2 of doxorubicin (or cumulative maximum dose of other another anthracycline vi. Known pulmonary disease with decreased diffusion capacity of lung for carbon monoxide (DLCO > 50%) and/or requiring oxygen ≤ 2 liters per minute vii. Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the Medical Monitor during screening and before randomization.

Exclusion criteria 7

1. 1. Subject was diagnosed with acute promyelocytic leukemia (APL).
2. 2. Subject has BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
3. 3. Subject has received previous therapy for AML, with the exception of the following: ● Emergency leukapheresis, ● Hydroxyurea, ● Preemptive treatment with retinoic acid prior to exclusion of APL ≤ 7 days, ● Growth factor or cytokine support, ● Steroids
4. 4. Subject has clinically active central nervous system leukemia.
5. 9. Subject requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP)3A/ P-glycoprotein (P-gp).
6. 13. Subject with mean Fridericia-corrected QT interval (QTcF) > 480 ms at screening based on central reading.
7. 14. Subject with a history of Long QT Syndrome at screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary Efficacy Endpoint: ● Overall Survival (OS)

Secondary endpoints 3

1. Key Secondary Efficacy Endpoint: ● Event-free survival (EFS)
2. Secondary Efficacy Endpoints: ● Best Response ● CR, CRc, CRh, CR/CRh ● Transfusion conversion rate; transfusion maintenance rate ● Leukemia-free survival (LFS) ● Duration of remission ● Patient-reported fatigue from BFI
3. Safety Endpoints: ● AEs ● Clinical laboratory (serum chemistry, hematology, coagulation and urinalysis) results ● Physical examinations ● Vital sign measurements ● ECGs ● ECOG performance scores

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Astellas Pharma Global Development Inc.

Sponsor organisation

Astellas Pharma Global Development Inc.

Address

2375 Waterview Drive

City

Northbrook

Postcode

60062-6111

Country

United States

Scientific contact point

Organisation

Astellas Pharma Global Development Inc.

Contact name

Clinical Trial Unit Head

Public contact point

Organisation

Astellas Pharma Global Development Inc.

Contact name

Clinical Trial Unit Head

Third parties 3

Locations

2 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications