Sorafenib Tosylate and Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia
This phase II clinical trial is studying the side effects and how well giving sorafenib tosylate together with chemotherapy works in treating older patients with acute myeloid leukemia (AML). Sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. 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. Giving sorafenib tosylate together with combination chemotherapy may kill more cancer cells.
Adult Acute Megakaryoblastic Leukemia (M7)
Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
Adult Acute Myeloblastic Leukemia Without Maturation (M1)
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Adult Erythroleukemia (M6a)
Adult Pure Erythroid Leukemia (M6b)
Secondary Acute Myeloid Leukemia
Untreated Adult Acute Myeloid Leukemia
Drug: daunorubicin hydrochloride
Drug: sorafenib tosylate
Procedure: bone marrow aspiration
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study Incorporating Sorafenib (IND 69896, NSC 724772) Into the Therapy of Patients >/= 60 Years of Age With FLT3 Mutated Acute Myeloid Leukemia|
- Overall survival (OS) rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Frequency and severity of adverse events assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||April 2011|
|Estimated Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
Experimental: Treatment (combination chemotherapy)
See detailed description.
Drug: daunorubicin hydrochloride
Other Names:Drug: sorafenib tosylate
Other Names:Drug: cytarabine
Other Names:Procedure: bone marrow aspiration
Undergo bone marrow aspirateProcedure: biopsy
Other Name: biopsiesOther: laboratory biomarker analysis
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I. To determine if the 1-year overall survival rate of patients age >= 60 with internal tandem duplications of fms-like tyrosine kinase (FLT3-ITD) AML treated with a sorafenib (sorafenib tosylate) containing induction and post-remission therapy is significantly higher than the historical 1-year overall survival rate of similar patients who were not treated with sorafenib.
I. To determine the rates of complete remission (CR), CR with incomplete count recovery (CRi), and cytogenetic complete remission (CCyR) to induction chemotherapy.
II. To determine the overall survival, event-free survival, and remission duration in patients treated on this study.
III. To describe the frequency and severity of adverse events for patients treated on this study.
IV. To describe the interaction of pre-treatment disease and patient characteristics including morphology, cytogenetics, immunophenotype, molecular genetic features, white blood cell (WBC) count and hemogram, and performance status on clinical outcomes.
V. To assess FLT3 ligand concentrations and FLT3 plasma inhibitory activity during treatment and determine the relationship to clinical outcomes.
VI. To describe the interaction of FLT3 mutation type (tyrosine kinase domain [TKD] vs. ITD) and allelic ratio on clinical outcomes.
VII. To characterize geriatric assessment measures in the context of a treatment trial for AML defined by: the observed distribution and number of missing values for each measurement.
VIII. To identify specific geriatric assessment measures which are independently associated with overall survival (OS), 30-day treatment-related mortality and key quality of life outcomes (number of days hospitalized, number of oncology clinic visits, admission to a nursing facility) in patients receiving induction chemotherapy for AML.
IX. To explore the impact of induction chemotherapy on physical, cognitive, psychosocial factors.
OUTLINE: This is a multicenter study.
INDUCTION THERAPY: Patients receive daunorubicin hydrochloride intravenously (IV) on days 1-3, cytarabine IV continuously on days 1-7, and sorafenib tosylate orally (PO) twice daily on days 1-7. Patients then undergo a bone marrow aspirate or biopsy on day 14.
Patients with persistent disease undergo a second remission induction therapy comprising daunorubicin hydrochloride IV on days 1-2, cytarabine IV continuously on days 1-5, and sorafenib tosylate PO twice daily on days 1-7. Patients who achieve complete response (CR)* proceed to consolidation therapy.
CONSOLIDATION THERAPY: Patients** receive cytarabine IV over 3 hours on days 1-5 and sorafenib tosylate PO twice daily on days 1-28. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with continued CR proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive sorafenib tosylate PO twice daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
NOTE: *Patients who achieve CR and who are eligible for hematopoietic stem cell transplantation (HSCT) are encouraged to enroll in CALGB 100103. Patients in CR who are unable or unwilling to undergo HSCT receive two courses of remission consolidation therapy.
NOTE: ** Patients in CR/complete remission with incomplete count recovery (CRi) who are unable or unwilling to complete remission consolidation therapy may proceed directly to maintenance therapy after consulting with the CALGB study chair.
Patients may undergo bone marrow aspirate, tumor biopsy, and/or blood sampling at baseline and periodically during study for cytogenetic, biomarker, and mutation analysis.
After completion of study therapy, patients are followed up every 2 months for 2 years, every 3 months for 2 years, and then yearly for at least 10 years.