Clinical Trial: Combination Chemotherapy and Dasatinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Phase II Study of Induction (Daunorubicin/Cytarabine) and Consolidation (High-Dose Cytarabine) Chemotherapy Plus Dasatinib (NSC #732517) and Continuation Therapy With Dasatinib Alone in Newly Diagnose

Brief Summary: This phase II trial studies the side effects and how well giving combination chemotherapy together with dasatinib works in treating patients with newly diagnosed acute myeloid leukemia. Drugs used in chemotherapy, such as daunorubicin hydrochloride and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with dasatinib may kill more cancer cells.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To assess the safety and tolerability of dasatinib with intensive induction therapy (daunorubicin hydrochloride and cytarabine), consolidation chemotherapy (high-dose cytarabine), and as single agent in maintenance therapy in patients with newly diagnosed core-binding factor acute myeloid leukemia (AML).

SECONDARY OBJECTIVES:

I. To assess clinical outcomes such as event-free survival (EFS), complete response (CR) rate, cumulative incidence of relapse (CIR), cumulative incidence of death (CID), disease-free survival (DFS), and overall survival (OS) of patients treated with these regimens.

II. To describe the frequency and severity of adverse events of patients treated on this study during induction, consolidation, and continuation therapy.

III. To describe the interaction of pretreatment disease and patient characteristics including morphology, cytogenetics, immunophenotype, molecular genetic features, white blood cell (WBC) count and hemogram, and performance status on clinical outcomes.

OUTLINE:

INDUCTION THERAPY (course 1): Patients receive daunorubicin hydrochloride intravenously (IV) on days 1-3, cytarabine IV continuously over 168 hours on days 1-7, and dasatinib orally (PO) once daily (QD) on days 8-21. Patients with responsive disease on day 21 undergo consolidation therapy, and patients with non-responsive disease on day 21 (bone marrow cellularity >= 20 % and leukemia blasts >= 5%) receive a second course of induction therapy.

INDUCTION THERAPY (course 2): Patients receive daunorubicin hydro
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: 30 Day Survival Rate [ Time Frame: 30 days ]

Percentage of participants who were alive 30 days after starting induction treatment.


Original Primary Outcome:

  • 30-day survival rate during induction therapy
  • Absence of pleural or pericardial effusion
  • Absence of liver toxicity that exceeds grade 2


Current Secondary Outcome:

  • Event-free Survival [ Time Frame: Up to 10 years ]

    Event free survival (EFS) is defined as the time from registration to failure to achieve complete remission (CR), relapse after CR is attained or death, whichever comes first. The median EFS with 95% CI was estimated using the Kaplan-Meier method,

    Complete remission (CR) is defined as: disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count > 1.0 x 10^9/L and platelet count > 100 x 10^9/L, and normal bone marrow differential (< 5% blasts).

  • Complete Response Rate [ Time Frame: Up to 10 years ]

    Percentage of participants who achieve a CR.

    CR is defined in the above outcome measure.

  • Cumulative Incidence of Relapse [ Time Frame: Up to 10 years ]
  • Cumulative Incidence of Death [ Time Frame: Up to 10 years ]
  • Disease-free Survival [ Time Frame: Up to 10 years ]
    Disease free survival (DFS) is defined as the time from achievement of CR to relapse or death, whichever comes first. The median DFS with 95% CI was estimated using the Kaplan-Meier method.
  • Overall Survival [ Time Frame: Up to 10 years ]
    Overall survival (OS) is defined as time from registration to death. The median OS with 95% CI was estimated using the Kaplan-Meier method.


Original Secondary Outcome:

  • Rate of early/hypoplastic death
  • Event-free survival
  • Complete Response Rate
  • Disease-free Survival
  • Overall Survival
  • Cumulative Incidence of Relapse


Information By: National Cancer Institute (NCI)

Dates:
Date Received: November 9, 2010
Date Started: December 2010
Date Completion:
Last Updated: April 4, 2017
Last Verified: February 2017