A Study of ASP2215 in Combination With Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia

NCT02236013 | Completed Phase 1

• 1 other identifier: 2215-CL-0103
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 10

Brief Summary

The purpose of this study is to describe the dose limiting toxicities (DLT) and define the maximum tolerated dose (MTD) of ASP2215 when combined with cytarabine/idarubicin or daunorubicin remission induction in a 7+3 schedule. Safety and tolerability of ASP2215 will also be evaluated. This study will also characterize the pharmacokinetics (PK) of ASP2215 when given in combination with cytarabine/idarubicin or cytarabine/daunorubicin remission induction and high-dose cytarabine (HiDAC) consolidation therapy in newly diagnosed acute myeloid leukemia as well as evaluate the effect of ASP2215 on the PK of cytarabine.

Conditions

Acute Myeloid Leukemia

Keywords

ASP2215; Daunorubicin; Gilteritinib; Acute Myeloid Leukemia; Idarubicin; Cytarabine

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability assessed by development of dose limiting toxicities, adverse events, and define maximum tolerated dose (MTD)

  up to 2.5 years after start of the treatment

Secondary Outcomes (2)

• Pharmacokinetics profile of ASP2215: AUC24, Cmax, Ctrough and tmax

  Days 8, 11, 17, and 28 for remission induction and Days 1, 2, and 15 for consolidation

• Pharmacokinetics of cytarabine: Css

  Days 3 and 8

Study Arms (4)

ASP2215 Dose Escalation (Part 1)

EXPERIMENTAL

Successive dose escalation cohorts will determine the maximum tolerated dose (MTD)

Drug: Gilteritinib; Drug: Idarubicin; Drug: Cytarabine

ASP2215 Dose Expansion (Part 2)

EXPERIMENTAL

Once the MTD has been established in Part 1, up to 20 subjects will be enrolled into an expansion cohort

Drug: Gilteritinib; Drug: Idarubicin; Drug: Cytarabine

Alternative Anthracycline and Schedule (Part 3)

EXPERIMENTAL

In Part 3, two cohorts will be enrolled to evaluate an alternative anthracycline and ASP2215 schedule

Drug: Gilteritinib; Drug: Idarubicin; Drug: Cytarabine; Drug: Daunorubicin

Continuous ASP2215 Exposure during Consolidation (Part 4)

EXPERIMENTAL

During Consolidation, ASP2215 will be given daily on day 1 up to day 56.

Drug: Gilteritinib; Drug: Idarubicin; Drug: Cytarabine; Drug: Daunorubicin

Interventions

Gilteritinib DRUG

Oral

Also known as: ASP2215

ASP2215 Dose Escalation (Part 1); ASP2215 Dose Expansion (Part 2); Alternative Anthracycline and Schedule (Part 3); Continuous ASP2215 Exposure during Consolidation (Part 4)

Idarubicin DRUG

lyophilized powder administered intravenously

ASP2215 Dose Escalation (Part 1); ASP2215 Dose Expansion (Part 2); Alternative Anthracycline and Schedule (Part 3); Continuous ASP2215 Exposure during Consolidation (Part 4)

Cytarabine DRUG

solution administered intravenously

ASP2215 Dose Escalation (Part 1); ASP2215 Dose Expansion (Part 2); Alternative Anthracycline and Schedule (Part 3); Continuous ASP2215 Exposure during Consolidation (Part 4)

Daunorubicin DRUG

solution administered intravenously

Alternative Anthracycline and Schedule (Part 3); Continuous ASP2215 Exposure during Consolidation (Part 4)

Eligibility Criteria

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

You may qualify if:

• Subject has a diagnosis of previously-untreated de novo acute myeloid leukemia (AML) according to WHO classification (2008) documented within 28 days prior to enrollment.
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Subject must meet the following criteria as indicated on the clinical laboratory tests.
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x institutional upper limit normal (ULN)
• Total serum bilirubin ≤ 1.5 x institutional ULN
• Serum creatinine ≤ 1.5 x institutional ULN or an estimated glomerular filtration rate (eGFR) of \> 50 ml/min as calculated by the Modification of Diet in Renal Disease (MDRD) equation.
• Subject is suitable for oral administration of study drug.
• Female subject must be either:
• Of non-child bearing potential:
• post-menopausal (defined as at least 1 year without any menses) prior to Screening, or
• documented surgically sterile or status post hysterectomy (at least 1 month prior to Screening)
• Or, if of childbearing potential,
• must agree not to try to become pregnant during the study and for 180 days after the final study drug administration, and
• must have a negative urine pregnancy test at Screening, and
• must use two forms of birth control\* (at least one of which must be a barrier method) starting at Screening and throughout the study period and for 180 days after the final study drug administration. \*Acceptable forms of birth control include:

You may not qualify if:

• Subject was diagnosed as acute promyelocytic leukemia (APL) or AML with good risk cytogenetics; t(8;21), inv(16) or t(16;16). (Subjects with pending cytogenetics that require treatment may enroll. Any subject that is found to have good risk cytogenetics after initiation of treatment will discontinue ASP2215 and be taken off trial).
• Subject has BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
• Subject has active malignant tumors other than AML or myelodysplastic syndrome (MDS).
• Subject has received previous therapy for AML, with the exception of the following:
• Emergency leukapheresis;
• Emergency treatment for hyperleukocytosis with hydroxyurea for ≤ 10 days;
• Growth factor or cytokine support;
• Steroids for the treatment of hypersensitivity or transfusion reactions.
• Subject has clinically active central nervous system leukemia.
• Subject has disseminated intravascular coagulation abnormality (DIC).
• Subject has had major surgery within 4 weeks prior to the first study dose.
• Subject has radiation therapy within 4 weeks prior to the first study dose.
• Subject has congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subject with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram performed within 3 months prior to study entry results in a left ventricular ejection fraction that is ≥ 45%.
• Subject requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP)3A.
• Subject requires treatment with concomitant drugs that are strong inhibitors or inducers of P glycoprotein (P-gp) with the exception of drugs that are considered absolutely essential for the care of the subject.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (10)

Site US10003

Los Angeles, California, 90095, United States

Location

Site US10013

New Haven, Connecticut, 06520, United States

Location

Site US10004

Chicago, Illinois, 60611, United States

Location

Site US10009

Westwood, Kansas, 66205, United States

Location

Site US10001

Baltimore, Maryland, 21231, United States

Location

Site US10002

New York, New York, 10032, United States

Location

Site US10014

Cleveland, Ohio, 44106, United States

Location

Site US10019

Oklahoma City, Oklahoma, 73104, United States

Location

Site US10006

Philadelphia, Pennsylvania, 19104, United States

Location

Site US10010

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• Pratz KW, Cherry M, Altman JK, Cooper BW, Podoltsev NA, Cruz JC, Lin TL, Schiller GJ, Jurcic JG, Asch A, Wu R, Hill JE, Gill SC, James AJ, Rich ES, Hasabou N, Perl AE, Levis MJ. Gilteritinib in Combination With Induction and Consolidation Chemotherapy and as Maintenance Therapy: A Phase IB Study in Patients With Newly Diagnosed AML. J Clin Oncol. 2023 Sep 10;41(26):4236-4246. doi: 10.1200/JCO.22.02721. Epub 2023 Jun 28.

  PMID: 37379495 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

gilteritinib; Idarubicin; Cytarabine; Daunorubicin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Executive Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

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: September 8, 2014
• First Posted: September 10, 2014
• Study Start: January 7, 2015
• Primary Completion: July 26, 2021
• Study Completion: July 26, 2021
• Last Updated: November 5, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

Locations

US (10)