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

NCT01876953 | Terminated Phase 1 Results DMC

• 2 other identifiers: 12393NCI-2013-01141
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (2)

• 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)

  From the first dose of Dasatinib through the DLT observation period (Day +28)

• 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.

  From the first cycle up to two years

Secondary Outcomes (2)

• Overall Survival (Phase II)

  Time from start of study therapy until death, or last contact, whichever comes first, assessed up to 2 years

• Event-free Survival (Phase II)

  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.

Study Arms (2)

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

EXPERIMENTAL

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.

Drug: cytarabine; Drug: idarubicin; Drug: dasatinib; Other: laboratory biomarker analysis

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

EXPERIMENTAL

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.

Drug: cytarabine; Drug: idarubicin; Drug: dasatinib; Other: laboratory biomarker analysis

Interventions

cytarabine DRUG

Given IV

Also known as: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside

Dasatinib 100mg/day + Cytarabine 200mg/m2/day + Idarubicin 12mg/m2/day; Dasatinib 140mg/day + Cytarabine 200mg/m2/day + Idarubicin 12mg/m2/day

idarubicin DRUG

Given IV

Also known as: 4-demethoxydaunorubicin, 4-DMDR, DMDR, IDA

Dasatinib 100mg/day + Cytarabine 200mg/m2/day + Idarubicin 12mg/m2/day; Dasatinib 140mg/day + Cytarabine 200mg/m2/day + Idarubicin 12mg/m2/day

dasatinib DRUG

Given PO

Also known as: BMS-354825, Sprycel

Dasatinib 100mg/day + Cytarabine 200mg/m2/day + Idarubicin 12mg/m2/day; Dasatinib 140mg/day + Cytarabine 200mg/m2/day + Idarubicin 12mg/m2/day

laboratory biomarker analysis OTHER

Correlative studies

Dasatinib 100mg/day + Cytarabine 200mg/m2/day + Idarubicin 12mg/m2/day; Dasatinib 140mg/day + Cytarabine 200mg/m2/day + Idarubicin 12mg/m2/day

Eligibility Criteria

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

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Congenital Abnormalities; Leukemia, Myeloid, Acute

Interventions

Cytarabine; Idarubicin; Dasatinib

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Ahmed Aribi
• Organization: City of Hope Medical Center

aaribi@coh.org

626-359-8111

Study Officials

• Ahmed Aribi

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2013
• First Posted: June 13, 2013
• Study Start: September 13, 2013
• Primary Completion: April 25, 2018
• Study Completion: April 25, 2018
• Last Updated: March 31, 2022
• Results First Posted: September 16, 2021

Record last verified: 2022-03

Locations

US (1)