Dasatinib, Cytarabine, and Idarubicin in Treating Patients With High-Risk Acute Myeloid Leukemia

NCT ID: NCT01876953

Last Updated: 2022-03-31

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-13
• Study Completion Date: 2018-04-25

Brief Summary

This phase I/II trial studies the side effects and best dose of dasatinib when given together with cytarabine and idarubicin hydrochloride and to see how well they work in treating patients with acute myeloid leukemia that is likely to come back or spread. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine and idarubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving dasatinib together with cytarabine and idarubicin hydrochloride may be a better treatment for acute myeloid leukemia.

Detailed Description

PRIMARY OBJECTIVES:

I. Of the dose levels studied, to determine the maximum tolerated dose of dasatinib when given in combination with cytarabine and idarubicin for treatment of high risk acute myeloid leukemia (AML). (Phase I)

II. To determine the anti-tumor activity of dasatinib when given in combination with cytarabine and idarubicin, as assessed by complete remission rate (CR) and remission duration. (Phase II)

SECONDARY OBJECTIVES:

I. To document CR and survival outcomes (overall, event-free). (Phase I)

II. To estimate the survival probabilities (overall and event-free) and cumulative incidence of relapse/progression. (Phase II)

III. To describe and summarize all toxicities by organ and severity. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of dasatinib, followed by a phase II study.

Patients receive cytarabine intravenously (IV) continuously over 168 hours on days 1-7, dasatinib orally (PO) once daily (QD) on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and then every 2 months for up to 2 years.

Conditions

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dasatinib 100mg/day + Cytarabine 200mg/m2/day + Idarubicin 12mg/m2/day

Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity.

Group Type: EXPERIMENTAL

cytarabine

Intervention Type: DRUG

Given IV

idarubicin

Intervention Type: DRUG

Given IV

dasatinib

Intervention Type: DRUG

Given PO

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Dasatinib 140mg/day + Cytarabine 200mg/m2/day + Idarubicin 12mg/m2/day

Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity.

Group Type: EXPERIMENTAL

cytarabine

Intervention Type: DRUG

Given IV

idarubicin

Intervention Type: DRUG

Given IV

dasatinib

Intervention Type: DRUG

Given PO

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

cytarabine

Given IV

Intervention Type: DRUG

idarubicin

Given IV

Intervention Type: DRUG

dasatinib

Given PO

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

ARA-C; arabinofuranosylcytosine; arabinosylcytosine; Cytosar-U; cytosine arabinoside; 4-demethoxydaunorubicin; 4-DMDR; DMDR; IDA; BMS-354825; Sprycel

Eligibility Criteria

Inclusion Criteria

• Patients diagnosed with AML meeting one of the following criteria:

• Newly diagnosed, age 60 and older
• High risk cytogenetics and molecular abnormalities (National Comprehensive Cancer Network [NCCN] criteria)
• Relapsed or refractory to prior chemotherapy
• Secondary AML
• Any prior chemotherapy must have been completed >= 2 weeks prior to day 1 of study treatment and the participant must have recovered to eligibility levels from prior toxicity

• Only one prior regimen is allowed for relapsed AML patients; note one prior regimen is defined as follows:

• Induction chemotherapy followed by consolidation is considered one regimen
• Induction chemotherapy followed by re-induction in case of persistent disease followed by consolidation is considered one regimen
• Hydroxyurea is allowed prior to day 1 of study treatment to keep white blood cell (WBC) below 20 K
• Karnofsky performance status >= 60%
• Total bilirubin < 1.5 x institutional upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
• Creatinine < 1.5 x institutional upper limit or normal OR creatinine clearance >= 60 mL/min for patients with creatinine levels above 1.5 x institutional upper limit of normal
• Ejection fraction (EF) >= 45%
• Ability to understand and sign a written informed consent document
• Patients should not be receiving any other investigational agents

Exclusion Criteria

• Patients with clinically significant illness which would compromise participation in the study, including, but not limited to: active or uncontrolled infection, immune deficiencies or confirmed diagnosis of human immunodeficiency virus (HIV) infection, active hepatitis B, active hepatitis C, or uncontrolled diabetes, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmias; or psychiatric illness/social situations that would limit compliance with study requirements
• Patients with additional (other than AML) currently active primary malignancy other than curatively treated carcinoma in situ (CIS) of the cervix, or basal or squamous cell carcinoma of the skin; patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy and disease free from prior malignancies for > 2 years
• Patients with active central nervous system (CNS) disease
• Patients with Chronic Myelogenous Leukemia (CML) in Myeloid blasts crisis
• Active infections, including opportunistic infections
• Women of childbearing potential (WOCBP) who have a positive serum pregnancy test within 14 days of the first administration of oral dasatinib

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ahmed Aribi

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

City of Hope Medical Center

Duarte, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2013-01141

Identifier Type: REGISTRY

Identifier Source: secondary_id

12393

Identifier Type: -

Identifier Source: org_study_id