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
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
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
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
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.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall survival (OS) rate
Cancer and Leukemia Group B
United States: Food and Drug Administration
|University of Iowa Hospitals and Clinics||Iowa City, Iowa 52242|
|Washington University School of Medicine||Saint Louis, Missouri 63110|
|Massachusetts General Hospital Cancer Center||Boston, Massachusetts 02114|
|Western Pennsylvania Hospital||Pittsburgh, Pennsylvania 15224|
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|North Shore University Hospital||Manhasset, New York 11030|
|Eastern Maine Medical Center||Bangor, Maine 04401|
|Weill Medical College of Cornell University||New York, New York 10021|
|Long Island Jewish Medical Center||New Hyde Park, New York 11040|
|Munson Medical Center||Traverse City, Michigan 49684|
|Brigham and Women's Hospital||Boston, Massachusetts 02115|
|Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center||Columbus, Ohio 43210-1240|
|Beebe Medical Center||Lewes, Delaware 19958|
|Mecosta County Medical Center||Big Rapids, Michigan 49307|
|Mountainview Medical||Berlin, Vermont 05602|
|Harold Alfond Center for Cancer Care||Augusta, Maine 04330|
|Union Hospital of Cecil County||Elkton MD, Maryland 21921|
|Dartmouth Hitchcock Medical Center||Lebanon, New Hampshire 03756|
|University Of Vermont||Burlington,, Vermont 05403|
|Virginia Commonwealth University||Richmond, Virginia|
|Florida Hospital||Orlando, Florida 32803|
|University of Chicago Comprehensive Cancer Center||Chicago, Illinois 60637-1470|
|Wake Forest University Health Sciences||Winston-Salem, North Carolina 27157|
|Evanston CCOP-NorthShore University HealthSystem||Evanston, Illinois 60201|
|Fort Wayne Medical Oncology and Hematology Inc - State Boulevard||Fort Wayne, Indiana 46845|
|Grand Rapids Clinical Oncology Program||Grand Rapids, Michigan 49503|
|Saint Mary's Health Care||Grand Rapids, Michigan 49503|
|Spectrum Health at Butterworth Campus||Grand Rapids, Michigan 49503|
|Mercy Health Partners-Mercy Campus||Muskegon, Michigan 49443|
|Cooper Hospital University Medical Center||Camden, New Jersey 08103|
|State University of New York Upstate Medical University||Syracuse, New York 13210|
|Wayne Memorial Hospital||Goldsboro, North Carolina 27534|
|Kinston Medical Specialists PA||Kinston, North Carolina 28501|
|University of Maryland Greenebaum Cancer Center||Baltimore, Maryland 21201|
|University of Missouri - Ellis Fischel||Columbia, Missouri 65203|
|Monter Cancer Center||Lake Success, New York 11042|
|Spectrum Health Reed City Hospital||Reed City, Michigan 49677|
|Cancer Care Associates-Mercy||Oklahoma City, Oklahoma 73120|
|Cancer and Leukemia Group B||Chicago, Illinois 60606|
|North Shore-LIJ Health System CCOP||Manhasset, New York 11030|
|Christiana Care Health System-Christiana Hospital||Newark, Delaware 19718|
|Bronson Battle Creek||Battle Creek, Michigan 49017|
|Cancer Care Associates-Norman||Norman, Oklahoma 73071|