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

Primary Purpose

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
cytarabine
idarubicin
dasatinib
laboratory biomarker analysis
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • City of Hope Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

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

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

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose of Dasatinib (Phase I)
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)
Complete Remission Rate (Phase II)
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

Overall Survival (Phase II)
Overall survival was measured from the first dose of Dasatinib to death from any cause or last contact, whichever comes first. It was estimated using the product-limit method of Kaplan and Meier.
Event-free Survival (Phase II)
Event-free survival was defined as time from the first dose of Dasatinib to relapse/progression, receipt of anti-leukemia therapy, death, or last contact, whichever comes first. It was estimated using the product-limit method of Kaplan and Meier.

Full Information

First Posted
June 11, 2013
Last Updated
March 28, 2022
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01876953
Brief Title
Dasatinib, Cytarabine, and Idarubicin in Treating Patients With High-Risk Acute Myeloid Leukemia
Official Title
Phase I/II Study of the Combination of Dasatinib With Chemotherapy for High Risk Acute Myeloid Leukemia (AML) Patients
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Terminated
Why Stopped
Due to the budget issues, the study discontinued at Phase II.
Study Start Date
September 13, 2013 (Actual)
Primary Completion Date
April 25, 2018 (Actual)
Study Completion Date
April 25, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dasatinib 100mg/day + Cytarabine 200mg/m2/day + Idarubicin 12mg/m2/day
Arm Type
Experimental
Arm Description
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.
Arm Title
Dasatinib 140mg/day + Cytarabine 200mg/m2/day + Idarubicin 12mg/m2/day
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
cytarabine
Other Intervention Name(s)
ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
idarubicin
Other Intervention Name(s)
4-demethoxydaunorubicin, 4-DMDR, DMDR, IDA
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
dasatinib
Other Intervention Name(s)
BMS-354825, Sprycel
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose of Dasatinib (Phase I)
Description
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
From the first dose of Dasatinib through the DLT observation period (Day +28)
Title
Complete Remission Rate (Phase II)
Description
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.
Time Frame
From the first cycle up to two years
Secondary Outcome Measure Information:
Title
Overall Survival (Phase II)
Description
Overall survival was measured from the first dose of Dasatinib to death from any cause or last contact, whichever comes first. It was estimated using the product-limit method of Kaplan and Meier.
Time Frame
Time from start of study therapy until death, or last contact, whichever comes first, assessed up to 2 years
Title
Event-free Survival (Phase II)
Description
Event-free survival was defined as time from the first dose of Dasatinib to relapse/progression, receipt of anti-leukemia therapy, death, or last contact, whichever comes first. It was estimated using the product-limit method of Kaplan and Meier.
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 two years.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ahmed Aribi
Organizational Affiliation
City of Hope Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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