A Study of ASP2215 (Gilteritinib) Combined With Atezolizumab in Patients With Relapsed or Treatment Refractory FMS-like Tyrosine Kinase (FLT3) Mutated Acute Myeloid Leukemia (AML)

NCT03730012 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 2215-CL-1101
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 12

Brief Summary

The purpose of this study was to determine the safety and tolerability of gilteritinib given in combination with atezolizumab in participants with relapsed or treatment refractory FMS-like tyrosine kinase 3 (FLT3) mutated AML and to determine the composite complete remission (CRc) rate for participants who either discontinued the study or completed 2 cycles of gilteritinib given in combination with atezolizumab. This study also evaluated pharmacokinetics (PK), response to treatment, remission and survival. Adverse events (AEs), clinical laboratory results, vital signs, electrocardiograms (ECGs), and Eastern Cooperative Oncology Group (ECOG) performance status scores were also assessed.

Conditions

Acute Myeloid Leukemia (AML); Acute Myeloid Leukemia With FMS-like Tyrosine Kinase (FLT3) Mutation

Keywords

AML; gilteritinib; ASP2215; Acute Myeloid Leukemia; FLT3

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose Limiting Toxicities (DLT)

  DLTs were defined as: * Confirmed Hy's Law case * Any Grade ≥ 3 non-hematologic or extramedullary toxicity with the following exceptions: * Anorexia or fatigue * Grade 3 nausea and/or vomiting if participant did not require tube feeding or total parenteral nutrition, or diarrhea if the events did not require or prolong hospitalization that could be managed to grade ≤ 2 with standard antiemetic or antidiarrheal medications used at prescribed dose within 7 days of onset. * Grade 3 mucositis that resolved to Grade ≤ 2 within 7 days of onset * Grade 3 fever with neutropenia, with or without infection * Grade 3 infection * Grade 3 infusion-related toxicity, if successfully managed and resolved within 72 hours.

  Day 1 up to 28 days

Secondary Outcomes (10)

• Composite Complete Remission (CRc) Rate

  From the date of first dose up to end of treatment (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab)

• Plasma Ctrough Concentration of Gilteritinib

  Pre-dose on C1D1, C1D8, C1D15, C2D1,C2D15, C3D1, C3D15, C4D1, C4D15, C5D1, C5D15, C6D1, C6D15

• Complete Remission (CR) Rate

  From the date of first dose up to end of treatment (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab)

• Complete Remission With Partial Hematologic Recovery (CRh) Rate

  From the date of first dose up to end of treatment (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab)

• Best Response Rate

  From the date of first dose up to end of treatment (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab)

Study Arms (2)

Gilteritinib 120 mg + Atezolizumab 420 mg

EXPERIMENTAL

Participants received 120 milligrams (mg) giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 420 mg adminstered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 535 days for gilteritinib and 112 days for atezolizumab).

Drug: gilteritinib; Drug: atezolizumab

Gilteritinib 120 mg + Atezolizumab 840 mg

EXPERIMENTAL

Participants received 120 mg giltertinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles in combination with atezolizumab 840 mg administered by intravenous infusion (over 60 minutes) once every 2 weeks of 28-day cycle until the participant no longer received clinical benefit from therapy, unacceptable toxicity occurred or the participant met a treatment discontinuation criterion (Maximum treatment duration was 126 days for gilteritinib and 70 days for atezolizumab).

Drug: gilteritinib; Drug: atezolizumab

Interventions

gilteritinib DRUG

Oral tablet

Also known as: ASP2215

Gilteritinib 120 mg + Atezolizumab 420 mg; Gilteritinib 120 mg + Atezolizumab 840 mg

atezolizumab DRUG

Intravenous infusion

Gilteritinib 120 mg + Atezolizumab 420 mg; Gilteritinib 120 mg + Atezolizumab 840 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is considered an adult according to local regulation at the time of signing informed consent form (ICF).
• Subject has defined AML by the World Health Organization (WHO) criteria (2017) and fulfills one of the following:
• Refractory to at least 1 cycle of induction chemotherapy
• Relapsed after achieving remission with a prior therapy
• Subject is positive for FLT3 mutation in bone marrow or blood after completion of the subject's last interventional treatment.
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at screening.
• Subject must meet the following criteria as indicated on the clinical laboratory tests:
• Serum Aspartate aminotransferase (AST) and Alanine Aminotransferease (ALT) ≤ 2.5 x upper limit of normal (ULN)
• Serum total bilirubin (TBL) ≤ 1.5 x ULN
• Serum creatinine ≤ 1.5 x ULN or an estimated glomerular filtration rate of \> 50 mL/min as calculated by the Modification of Diet in Renal Disease equation.
• Subject is suitable for oral administration of study drug.
• A female subject is eligible to participate if she is not pregnant and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 180 days after the final study drug administration.
• Female subject must agree not to breastfeed starting at screening and throughout the study period, and for at least 180 days after the final study drug administration.

You may not qualify if:

• Subject was diagnosed as acute promyelocytic leukemia.
• Subject has BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
• Subject has AML secondary to prior chemotherapy for other neoplasms (except for myelodysplastic syndrome).
• Subject has clinically active central nervous system leukemia.
• Subject has uncontrolled or significant cardiovascular disease, including:
• A myocardial infarction within 12 months
• Uncontrolled angina within 6 months
• History of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, torsades de pointes) or any history of arrhythmia
• Uncontrolled hypertension
• Subject has baseline left ventricular ejection fraction that is ≥ 45%.
• Subject has mean triplicate Fridericia-corrected QT interval (QTcF) \> 450 ms at Screening based on central reading.
• Subject has congenital or acquired Long QT Syndrome at screening.
• Subject has hypokalemia and/or hypomagnesemia at screening.
• Subject has been diagnosed with another malignancy that requires concurrent treatment or hepatic malignancy regardless of the need for treatment.
• Subject has clinically significant coagulation abnormality unless secondary to AML.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (12)

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

University of Chicago

Chicago, Illinois, 60037, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Roswell Park Cancer Institute (RPCI)

Buffalo, New York, 14263, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

The Ohio State University Comprehensive Cancer Center (OSUCCC)

Columbus, Ohio, 43210, United States

Location

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Simmons Comprehensive Cancer Center

Dallas, Texas, 75390, United States

Location

University of Texas MD Anderson

Houston, Texas, 77030, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Links

• Link to results on the Astellas Clinical Study Results website.
• Link to plain language summary of the study on the Trial Results Summaries website

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

gilteritinib; atezolizumab

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Clinical trial Disclosure
• Organization: Astellas Pharma Global Development, Inc

astellas.resultsdisclosure@astellas.com

800-888-7704

Study Officials

• Executive Medical Director

  Astellas Pharma Global Development

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: November 1, 2018
• First Posted: November 5, 2018
• Study Start: June 19, 2019
• Primary Completion: May 14, 2021
• Study Completion: June 15, 2021
• Last Updated: November 29, 2024
• Results First Posted: June 24, 2022

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)