Combination Chemotherapy and Dasatinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
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Purpose
This phase II trial is studying 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
| Condition | Intervention | Phase |
|---|---|---|
|
Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Secondary Acute Myeloid Leukemia Untreated Adult Acute Myeloid Leukemia |
Drug: daunorubicin hydrochloride Drug: cytarabine Drug: dasatinib |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase II Study of Induction (Daunorubicin/Cytarabine) and Consolidation (High-Dose Cytarabine) Chemotherapy Plus Dasatinib (NSC #732517, IND #73969) and Continuation Therapy With Dasatinib Alone in Newly Diagnosed Patients With Core Binding Factor Acute Myeloid Leukemia (AML) |
- Survival rate during induction therapy [ Time Frame: 30 days ] [ Designated as safety issue: No ]
- Absence of pleural or pericardial effusion [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]The frequency and severity of adverse events for patients treated on this study during induction, consolidation and continuation therapy will be tabulated.
- Absence of liver toxicity that exceeds grade 2 [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]The frequency and severity of adverse events for patients treated on this study during induction, consolidation and continuation therapy will be tabulated.
- Rate of early/hypoplastic death [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]The frequency and severity of adverse events for patients treated on this study during induction, consolidation and continuation therapy will be tabulated.
- Event-free survival [ Time Frame: From registration to failure to achieve CR, relapse after CR is attained, or death whichever comes first, assessed up to 10 years ] [ Designated as safety issue: No ]
- Complete response rate [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
- Cumulative incidence of relapse [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
- Cumulative incidence of death [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
- Disease-free survival [ Time Frame: From achievement of CR to relapse or death whichever comes first, assessed up to 10 years ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: From registration to death, assessed up to 10 years ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 59 |
| Study Start Date: | December 2010 |
| Estimated Primary Completion Date: | July 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment (daunorubicin hydrochloride, cytarabine, dasatinib)
INDUCTION THERAPY (course 1): Patients receive daunorubicin hydrochloride IV on days 1-3, cytarabine IV continuously over 168 hours on days 1-7, and dasatinib PO once daily 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 hydrochloride IV on days 1-3, cytarabine IV continuously over 120 hours on days 1-5, and dasatinib PO once a day on days 6-19. Patients achieving complete response receive consolidation therapy. CONSOLIDATION THERAPY: Patients receive high-dose cytarabine IV over 3 hours on days 1, 3, and 5, and dasatinib PO once daily on days 6-26. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients in complete remission receive continuation therapy. |
Drug: daunorubicin hydrochloride
Given IV
Other Names:
Drug: cytarabine
Given IV
Other Names:
Drug: dasatinib
Given PO
Other Names:
|
Detailed Description:
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 rate (CR), 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 count and hemogram, and performance status on clinical outcomes.
OUTLINE: This is a multicenter study.
INDUCTION THERAPY (course 1): Patients receive daunorubicin hydrochloride IV on days 1-3, cytarabine IV continuously over 168 hours on days 1-7, and dasatinib orally (PO) once daily 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 hydrochloride IV on days 1-3, cytarabine IV continuously over 120 hours on days 1-5, and dasatinib PO once a day on days 6-19. Patients achieving complete response receive consolidation therapy.
CONSOLIDATION THERAPY: Patients receive high-dose cytarabine IV over 3 hours on days 1, 3, and 5, and dasatinib PO once daily on days 6-26. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients in complete remission receive continuation therapy.
CONTINUATION THERAPY: Patients receive dasatinib PO on days 1-28. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up every 2 months for 2 years, every 3 months for 2 years, and then every year for a up to 10 years.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Newly diagnosed acute myeloid leukemia (AML)
Molecular diagnosis of core-binding factor (CBF) AML by RT-PCR positive for any of the following:
- RUNX1-RUNX1T1 fusion transcript resulting from t(8;21)(q22;q22) or a variant form
- CBFB-MYH11 fusion transcript resulting from inv(16)(p13.1q22) ort(16;16)(p13.1;q22) (any % bone marrow or blood blasts render the diagnosis of CBFAML based on the WHO classification)
- AML with a history of antecedent myelodysplasia (MDS) allowed
- Patients who have developed therapy-related myeloid neoplasm (t-MN) after prior radiotherapy or chemotherapy for another cancer or disorder allowed
- Must be registered on CALGB-8461 and CALGB-20202 protocols
- May also be registered on CALGB-9665
- Bilirubin < 2.5 times upper limit of normal
- Not pregnant or nursing
- Negative pregnancy test
Fertile patients must agree to use two acceptable methods of birth control before, during, and for ≥ 12 weeks after treatment is complete:
- One highly effective method (e.g., IUD, hormonal, tubal ligation, or partner's vasectomy)
- One additional effective method (e.g., latex condom, diaphragm, or cervical cap)
- Left ventricular ejection fraction >= lower limit of institutional normal by MUGA or ECHO scan
- No myocardial infarction within 6 months
- No ventricular tachyarrhythmia within 6 months
- No major conduction abnormality (unless a cardiac pacemaker is present)
- No patients with congenital QT syndrome or non-congenital QTc prolongation (≥ 480 msecs) that cannot be corrected by infusion of electrolytes and/or discontinuation of other medications prior to start of treatment
- No concurrent proton pump inhibitors
No prior chemotherapy for leukemia or myelodysplasia except the following:
- Emergency leukapheresis
- Emergency treatment for hyperleukocytosis with hydroxyurea
- Cranial radiotherapy for CNS leukostasis (one dose only)
- Growth factor and/or cytokine support and/or non-cytotoxic molecular-targeted agents
Contacts and Locations
Show 64 Study Locations| Principal Investigator: | Guido Marcucci | Cancer and Leukemia Group B |
More Information
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT01238211 History of Changes |
| Other Study ID Numbers: | NCI-2011-02615, CALGB 10801, U10CA031946 |
| Study First Received: | November 9, 2010 |
| Last Updated: | February 25, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Myeloid, Acute Leukemia, Myeloid Myelodysplastic Syndromes Preleukemia Neoplasms by Histologic Type Neoplasms Bone Marrow Diseases Hematologic Diseases Precancerous Conditions Cytarabine Daunorubicin 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 Antibiotics, Antineoplastic Protein Kinase Inhibitors Enzyme Inhibitors |
ClinicalTrials.gov processed this record on May 16, 2013