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

This study has suspended participant recruitment.
(Pending DSMB approval)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT01876953
First received: June 11, 2013
Last updated: July 2, 2014
Last verified: July 2014
  Purpose

This phase I/II trial studies the side effects and best dose of dasatinib when given together with cytarabine and idarubicin and to see how well they work in treating patients with high-risk acute myeloid leukemia. 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, 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 may be an effective treatment for acute myeloid leukemia.


Condition Intervention Phase
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
Drug: cytarabine
Drug: idarubicin
Drug: dasatinib
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of the Combination of Dasatinib With Chemotherapy for High Risk Acute Myeloid Leukemia (AML) Patients

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Maximum tolerated dose of dasatinib, determined according to incidence of dose limiting toxicity (DLT), graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I) [ Time Frame: Up to 42 days ] [ Designated as safety issue: Yes ]
  • CR rate (Phase II) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Remission rates will be calculated as the percent of evaluable patients that have a confirmed CR, and exact 95% confidence intervals will be calculated for these estimates.


Secondary Outcome Measures:
  • Remission duration (Phase II) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Will be estimated using the product-limit method of Kaplan and Meier.

  • Overall survival (Phase II) [ Time Frame: Time from start of study therapy until death, or last contact, whichever comes first, assessed up to 2 years ] [ Designated as safety issue: No ]
    Will be estimated using the product-limit method of Kaplan and Meier.

  • Event-free survival (Phase II) [ Time Frame: Time from start of study therapy until death, relapse/progression, receipt of anti-leukemia therapy, or last contact, whichever comes first, assessed up to 2 years ] [ Designated as safety issue: No ]
    Will be estimated using the product-limit method of Kaplan and Meier.

  • Cumulative incidence of relapse/progression (Phase II) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Incidence of toxicities, graded according to NCI CTCAE version 4.0(Phase II) [ Time Frame: Up to 30 days ] [ Designated as safety issue: Yes ]
    Observed toxicities will be summarized in terms of type (organ affected or laboratory determination) severity (by NCI CTCAE v4.0), date of onset, duration, reversibility, and attribution. Tables will be created to summarize these toxicities and side effects.


Estimated Enrollment: 52
Study Start Date: September 2013
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (cytarabine, idarubicin, and dasatinib)
Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy in the absence of unacceptable toxicity.
Drug: cytarabine
Given IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: idarubicin
Given IV
Other Names:
  • 4-demethoxydaunorubicin
  • 4-DMDR
  • DMDR
  • IDA
Drug: dasatinib
Given PO
Other Names:
  • BMS-354825
  • Sprycel
Other: laboratory biomarker analysis
Correlative studies

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 IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01876953

Locations
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Ahmed Aribi City of Hope Medical Center
  More Information

No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT01876953     History of Changes
Other Study ID Numbers: 12393, NCI-2013-01141
Study First Received: June 11, 2013
Last Updated: July 2, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Idarubicin
Dasatinib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014