A Phase II Study of Dasatinib (Sprycel®) (IND #73969, NSC #732517) as Primary Therapy Followed by Transplantation for Adults >/= 18 Years With Newly Diagnosed Ph+ Acute Lymphoblastic Leukemia by CALGB, ECOG and SWOG
I. Estimate the disease-free survival (DFS) and overall survival (OS) profiles in newly
diagnosed patients 18 years or older who have Ph+ (BCR/ABL+) ALL receiving sequential
dasatinib followed by allogeneic or autologous HCT or chemotherapy followed by dasatinib
I. Compare the OS and DFS profiles for each of the three cohorts to those from similar
populations from other studies.
II. Determine the ability of dasatinib to produce or maintain a BCR/ABL-negative status, as
judged by Q-PCR following sequential dasatinib, chemotherapy, and HCT.
III. Determine the feasibility of collecting adequate peripheral blood stem cells for
autologous HCT following dasatinib therapy and assess for residual Ph+ (BCR/ABL+) cells by
Q-PCR.Study the safety and efficacy of autologous HCT following therapy with dasatinib.
IV. Study the safety and efficacy of reduced-intensity preparatory regimen followed by an
allogeneic HCT following induction therapy with dasatinib.
V. Study the safety and efficacy of dasatinib maintenance administered after allogeneic or
autologous HCT or chemotherapy.
VI. Correlate plasma and CSF levels of dasatinib when given orally during induction.
REMISSION INDUCTION THERAPY (RIT): Patients receive dasatinib orally (PO) daily continuously
and dexamethasone PO or intravenously (IV) on days 1-7.
EARLY INTENSIFICATION THERAPY: Patients with bone marrow =< 20% blasts are assigned to
cohort A and patients with bone marrow > 20% blasts are assigned to cohort B.
COHORT A: Patients receive dasatinib and dexamethasone as in RIT.
COHORT B: Patients receive dasatinib and dexamethasone as in RIT, and vincristine sulfate IV
and daunorubicin hydrochloride IV on days 1, 8, and 15. Patients who do NOT achieve a
complete response (CR) or CR with incomplete hematologic recovery based on bone marrow
continue on to second induction therapy; patients who achieve a hematologic and morphologic
CR continue on to CNS prophylaxis therapy.
SECOND INDUCTION THERAPY: Patients receive dasatinib and dexamethasone as in RIT,
cyclophosphamide IV on day 1, daunorubicin hydrochloride IV and vincristine sulfate IV on
days 1 and 8, and filgrastim subcutaneously (SC) beginning on day 9 and continuing for >= 7
days or one dose of pegfilgrastim on day 9.
CNS PROPHYLAXIS THERAPY: Patients receive dasatinib PO daily continuously during CNS
prophylaxis therapy; methotrexate intrathecally (IT), vincristine sulfate IV, and
methotrexate IV over 3 hours on days 1, 15, and 29; methotrexate PO every 6 hours for a
total of 4 doses each on days 1-2, 15-16, and 29-30; leucovorin calcium IV on days 2, 16,
and 30; and leucovorin PO calcium every 6 hours for a total of 8 doses each on days 3-4,
17-18, and 31-32.
TRANSPLANTATION OR ALTERNATIVE CHEMOTHERAPY AND MAINTENANCE THERAPY: Patients aged 50-70
years with an HLA-matched related or unrelated donor are assigned to allogeneic
transplantation, patients aged 50-70 years without an HLA-matched related or unrelated donor
are assigned to autologous transplantation, and patients aged > 70 years or who are not
transplantation candidates are assigned to alternative chemotherapy.
ALLOGENEIC TRANSPLANTATION: Patients receive fludarabine phosphate IV over 30 minutes and
alemtuzumab IV over 30 minutes on days -7 through -3 and melphalan IV over 30 minutes on day
-2. Patients undergo allogeneic peripheral blood stem cell transplantation (PBSCT) on day 0.
Patients then receive filgrastim SC beginning on day 1 and continuing until count recovery
and tacrolimus IV or PO beginning on day -2 and beginning to taper on day 100 (for matched
related donors) or day 180 (for mismatched related or unrelated donors). Beginning on day
30, patients receive dasatinib PO daily as maintenance therapy. Treatment continues for >=
12 months in the absence of disease progression.
MOBILIZATION: Patients receive etoposide phosphate IV continuously on days 1-4, high-dose
cytarabine IV over 2 hours every 12 hours for a total of 8 doses on days 1-4, and filgrastim
SC once or twice daily beginning on day 14 and continuing until peripheral blood stem cell
collection is complete or WBC > 50,000/μL.
LEUKAPHERESIS: Patients undergo leukapheresis beginning when WBC > 10,000/μL for a target
collection of >= 5 x 10^6 CD34+ cells/kg. After completion of stem cell collection, patients
receive dasatinib PO twice daily until 3 days before transplantation.
TRANSPLANTATION: Beginning >= 4 weeks after recovery from toxicity related to previous
treatment, patients receive melphalan IV over 30 minutes on days -2 and -1. Patients undergo
autologous PBSCT on day 0. Patients then receive filgrastim SC beginning on day 0 and
continuing until count recovery.
MAINTENANCE THERAPY: Beginning on day 30, patients receive dasatinib PO once daily.
Treatment continues for >= 12 months in the absence of disease progression.
ALTERNATIVE CHEMOTHERAPY: Beginning 3-10 days after completion of CNS prophylaxis therapy,
patients receive etoposide phosphate IV continuously on days 1-4, high-dose cytarabine IV
over 2 hours every 12 hours for a total of 8 doses on days 1-4, and filgrastim SC once or
twice daily beginning on day 14 and continuing until count recovery.
MAINTENANCE THERAPY: Patients receive dasatinib PO once daily beginning on day 30. Patients
also receive vincristine sulfate IV every 4 weeks, dexamethasone for 5 days every 4 weeks,
mercaptopurine PO once daily, and methotrexate PO once weekly. Treatment continues for >= 12
months in the absence of disease progression.
NOTE: Patients with CNS leukemia or testicular disease may receive additional treatment.
After completion of study treatment, patients are followed up every month for 1 year, every
3 months for 2 years, every 6 months for 2 years, and every year for 5 years.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Disease-free survival (DFS)
Estimated using the Kaplan-Meier estimator. Proportions will be estimated using point as well as interval estimators. All interval estimators will be constructed using the finite sample size sampling distribution at the unadjusted two-sided level of 0.05.
Cancer and Leukemia Group B
United States: Food and Drug Administration
|Roswell Park Cancer Institute||Buffalo, New York 14263|
|Washington University School of Medicine||Saint Louis, Missouri 63110|
|Boulder Community Hospital||Boulder, Colorado 80301-9019|
|Swedish Medical Center||Englewood, Colorado 80110|
|Sky Ridge Medical Center||Lone Tree, Colorado 80124|
|North Shore University Hospital||Manhasset, New York 11030|
|Eastern Maine Medical Center||Bangor, Maine 04401|
|University of Nebraska Medical Center||Omaha, Nebraska 68198-3330|
|Via Christi Regional Medical Center||Wichita, Kansas 67214|
|Wesley Medical Center||Wichita, Kansas 67214|
|Weill Medical College of Cornell University||New York, New York 10021|
|Long Island Jewish Medical Center||New Hyde Park, New York 11040|
|North Colorado Medical Center||Greeley, Colorado 80631|
|McKee Medical Center||Loveland, Colorado 80539|
|Cancer Center of Kansas - Dodge City||Dodge City, Kansas 67801|
|Cancer Center of Kansas - Salina||Salina, Kansas 67042|
|Cancer Center of Kansas - Wellington||Wellington, Kansas 67152|
|Associates in Womens Health||Wichita, Kansas 67203|
|Cancer Center of Kansas - Winfield||Winfield, Kansas 67156|
|Beebe Medical Center||Lewes, Delaware 19958|
|Hematology and Oncology Associates||Chicago, Illinois 60611|
|Exempla Lutheran Medical Center||Wheat Ridge, Colorado 80033|
|Lawrence Memorial Hospital||Lawrence, Kansas 66044|
|Longmont United Hospital||Longmont, Colorado 80501|
|Harold Alfond Center for Cancer Care||Augusta, Maine 04330|
|Union Hospital of Cecil County||Elkton MD, Maryland 21921|
|Northwestern University||Chicago, Illinois 60611|
|University of Rochester||Rochester, New York 14642|
|Dartmouth Hitchcock Medical Center||Lebanon, New Hampshire 03756|
|Presbyterian - Saint Lukes Medical Center - Health One||Denver, Colorado 80218|
|Wichita CCOP||Wichita, Kansas 67214-3882|
|Florida Hospital||Orlando, Florida 32803|
|University of Chicago Comprehensive Cancer Center||Chicago, Illinois 60637-1470|
|Littleton Adventist Hospital||Littleton, Colorado 80122|
|Wake Forest University Health Sciences||Winston-Salem, North Carolina 27157|
|The Medical Center of Aurora||Aurora, Colorado 80012|
|Penrose-Saint Francis Healthcare||Colorado Springs, Colorado 80907|
|Saint Anthony Central Hospital||Denver, Colorado 80204|
|Exempla Saint Joseph Hospital||Denver, Colorado 80218|
|Saint Mary Corwin Medical Center||Pueblo, Colorado 81004|
|Provena Saint Mary's Hospital||Kankakee, Illinois 60901|
|North Shore Hematology Oncology||Libertyville, Illinois 60048|
|Hematology Oncology Associates of Illinois - Skokie||Skokie, Illinois 60076|
|Fort Wayne Medical Oncology and Hematology Inc - State Boulevard||Fort Wayne, Indiana 46845|
|Cancer Center of Kansas - El Dorado||El Dorado, Kansas 67042|
|Cancer Center of Kansas-Wichita Medical Arts Tower||Wichita, Kansas 67208|
|Cancer Center of Kansas - Main Office||Wichita, Kansas 67214|
|Cooper Hospital University Medical Center||Camden, New Jersey 08103|
|Monter Cancer Center||Lake Success, New York 11042|
|Gundersen Lutheran||La Crosse, Wisconsin 54601|
|The Jewish Hospital||Cincinnati, Ohio 45236|
|Stanford University Hospitals and Clinics||Stanford, California 94305|
|North Shore-LIJ Health System CCOP||Manhasset, New York 11030|
|Christiana Care Health System-Christiana Hospital||Newark, Delaware 19718|
|Illinois Cancer Specialists-Niles||Niles, Illinois 60714|