Phase II Study of Combination of Hyper-CVAD and Dasatinib With or Without Allogeneic Stem Cell Transplant in Patients With Philadelphia (Ph) Chromosome Positive and/or Bcr-Abl Positive Acute Lymphoblastic Leukemia (ALL) (A BMT Study).
PRIMARY OBJECTIVES:
I. To test whether the relapse-free survival after allogeneic stem cell transplantation
among Philadelphia chromosome positive and/or BCR/ABL positive acute lymphoblastic leukemia
(ALL) patients given an intensive short-term chemotherapy regimen of hyper-CVAD in
combination with the tyrosine kinase inhibitor dasatinib is sufficiently high to warrant
further investigation.
SECONDARY OBJECTIVES:
I. To test whether the continuous complete remission rate for previously untreated
Philadelphia chromosome positive and/or BCR/ABL positive acute lymphoblastic leukemia (ALL)
patients given an intensive short-term chemotherapy regimen of hyper-CVAD in combination
with the tyrosine kinase inhibitor dasatinib is sufficiently high to warrant phase III
investigation.
II. To investigate in a preliminary manner the relative effectiveness of minimal residual
disease (MRD) detection using real-time quantitative polymerase chain reaction (PCR) for
BCR/ABL versus flow cytometry to predict the outcome of patients treated by the hyper-CVAD +
dasatinib regimen and/or allogeneic stem cell transplant.
TERTIARY OBJECTIVES:
I. To estimate the frequency and severity of toxicities of the intensive short-term
chemotherapy regimen in these patients.
II. To estimate the overall survival of all patients on this study.
OUTLINE: This is a multicenter study.
Patients are stratified according to prior treatment and response (untreated vs achieved
complete remission [CR] with or without [CRi] hematopoietic recovery vs treated, refractory,
and no CR or CRi).
INDUCTION/CONSOLIDATION THERAPY: All patients receive both of the following regimens in
alternating courses:
COURSES 1, 3, 5, 7 or 3, 5, 7, 9: Patients receive cyclophosphamide intravenously (IV) over
3 hours twice daily (BID) on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4;
vincristine sulfate IV over 30 minutes on days 4 and 11; dexamethasone IV or orally (PO)
once daily (QD) on days 1-4 and 11-14; dasatinib PO QD on days 1-14; cytarabine
intrathecally (IT) on day 7; methotrexate IT on day 2; and filgrastim (G-CSF) subcutaneously
(SC) QD or BID.
COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 24 hours on day 1;
methylprednisolone IV over 30 minutes BID on days 1-3; dasatinib PO QD on days 1-14;
high-dose cytarabine IV over 2 hours BID on days 2-3; leucovorin calcium IV on days 2 or 3;
methotrexate IT on day 2; cytarabine IT on day 7; and G-CSF SC QD or BID.
Treatment repeats every 14-21 days for 8 courses in the absence of disease progression,
unacceptable toxicity, or if patient achieves CR or CRi.
MAINTENANCE THERAPY*: Patients receive vincristine sulfate IV over 30 minutes on day 1,
prednisone PO QD on days 1-5, and dasatinib PO QD on days 1-28.
Treatment repeats every month for 24 courses in the absence of disease progression or
unacceptable toxicity or until the transplant is ready.
INTENSIFICATION: For courses 6 and 13, patients receive cyclophosphamide IV over 3 hours BID
on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV
over 30 minutes on days 4 and 11; dexamethasone IV or PO QD on days 1-4 and 11-14; dasatinib
PO QD on days 1-14; and G-CSF SC QD or BID.
NOTE: *Only if transplantation is not ready after induction/consolidation therapy or
patients are not undergoing a transplant.
ALLOGENEIC STEM CELL TRANSPLANTATION (FOR PATIENTS ACHIEVING CR OR CRi):
CONDITIONING REGIMEN: Patients receive 1 of the following regimens:
REGIMEN A: Patients receive total-body irradiation (TBI) QD on days -7 to -4 and
cyclophosphamide IV on days -3 and -2.
REGIMEN B: Patients receive TBI BID on days -6 to -4 and cyclophosphamide IV on days -3 and
-2.
REGIMEN C: Patients receive cyclophosphamide IV on days -7 and -6 and TBI QD on days -4 to
-1.
REGIMEN D: Patients receive cyclophosphamide IV on days -6 and -5 and TBI BID on days -3 to
-1.
REGIMEN E: Patients receive TBI QD on days -7 to -4 and etoposide IV on day -3.
REGIMEN F: Patients receive TBI BID on days -6 to -4 and etoposide IV on day -3.
ALLOGENEIC STEM CALL TRANSPLANTATION: Patients undergo allogeneic stem cell transplantation
on day 0.
GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive 1 of the following regimens:
REGIMEN A: Patients receive sirolimus PO and tacrolimus IV continuously (changing to PO BID)
beginning on day -3 and continuing for 6 months.
REGIMEN B: Patients receive tacrolimus IV continuously (changing to PO BID) and continuing
for 6 months, and methotrexate IV on days 1, 3, 6, and 11.
SINGLE-AGENT THERAPY: After completion of maintenance therapy or beginning on day 100
post-transplantation, patients receive dasatinib PO QD for up to 5 years.
Bone marrow and blood samples are collected periodically for cytogenetic analysis by PCR and
flow cytometry.
After completion of study therapy, patients are followed every 6 months for up to 5 years.
Interventional
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Probability of relapse-free survival (RFS)
Will be estimated using the method of Kaplan-Meier.
12 months
No
Farhad Ravandi-Kashani
Principal Investigator
Southwest Oncology Group
United States: Food and Drug Administration
NCI-2009-00800
NCT00792948
September 2009
Name | Location |
---|---|
Albert Einstein College of Medicine | Bronx, New York 10461 |
Louisiana State University | New Orleans, Louisiana 70112-2282 |
Johns Hopkins University | Baltimore, Maryland 21205 |
Cleveland Clinic Foundation | Cleveland, Ohio 44195 |
Roswell Park Cancer Institute | Buffalo, New York 14263 |
Mayo Clinic | Rochester, Minnesota 55905 |
Washington University School of Medicine | Saint Louis, Missouri 63110 |
Medical University of South Carolina | Charleston, South Carolina 29425-0721 |
University of Washington Medical Center | Seattle, Washington 98195-6043 |
Abramson Cancer Center of the University of Pennsylvania | Philadelphia, Pennsylvania 19104-4283 |
Avera Cancer Institute | Sioux Falls, South Dakota 57105 |
Vanderbilt-Ingram Cancer Center | Nashville, Tennessee 37232-6838 |
Loyola University Medical Center | Maywood, Illinois 60153 |
LDS Hospital | Salt Lake City, Utah 84143 |
Via Christi Regional Medical Center | Wichita, Kansas 67214 |
Wesley Medical Center | Wichita, Kansas 67214 |
University of Oklahoma Health Sciences Center | Oklahoma City, Oklahoma 73104 |
Group Health Cooperative | Seattle, Washington 98112 |
Great Falls Clinic | Great Falls, Montana 59405 |
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle, Washington 98109 |
Montefiore Medical Center | Bronx, New York 10467-2490 |
Lewistown Hospital | Lewistown, Pennsylvania 17044 |
Mount Nittany Medical Center | State College, Pennsylvania 16803 |
Cancer Center of Kansas - Chanute | Chanute, Kansas 66720 |
Cancer Center of Kansas - Dodge City | Dodge City, Kansas 67801 |
Cancer Center of Kansas - Newton | Newton, Kansas 67114 |
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 |
Munson Medical Center | Traverse City, Michigan 49684 |
Bozeman Deaconess Hospital | Bozeman, Montana 59715 |
Kalispell Regional Medical Center | Kalispell, Montana 59901 |
Avera McKennan Hospital and University Health Center | Sioux Falls, South Dakota 57105 |
American Fork Hospital | American Fork, Utah 84003 |
Logan Regional Hospital | Logan, Utah 84321 |
McKay-Dee Hospital Center | Ogden, Utah 84403 |
Harborview Medical Center | Seattle, Washington 98104 |
Cancer Care Northwest - Spokane South | Spokane, Washington 99202 |
Welch Cancer Center | Sheridan, Wyoming 82801 |
Baylor University Medical Center | Dallas, Texas 75246 |
City of Hope Medical Center | Duarte, California 91010 |
Hematology and Oncology Associates | Chicago, Illinois 60611 |
Salina Regional Health Center | Salina, Kansas 67401 |
Mecosta County Medical Center | Big Rapids, Michigan 49307 |
Grandview Hospital | Dayton, Ohio 45405 |
Hematology Oncology Associates of Illinois-Highland Park | Highland Park, Illinois 60035 |
Miami Valley Hospital | Dayton, Ohio 45409 |
Cancer Center of Kansas - Fort Scott | Fort Scott, Kansas 66701 |
Cancer Center of Kansas-Independence | Independence, Kansas 67301 |
Lawrence Memorial Hospital | Lawrence, Kansas 66044 |
Bozeman Deaconess Cancer Center | Bozeman, Montana 59715 |
Wayne Hospital | Greenville, Ohio 45331 |
Clinton Memorial Hospital | Wilmington, Ohio 45177 |
Wenatchee Valley Medical Center | Wenatchee, Washington 98801-2028 |
Rocky Mountain Oncology | Casper, Wyoming 82609 |
Greene Memorial Hospital | Xenia, Ohio 45385 |
Memorial Medical Center | Springfield, Illinois 62781 |
Metro Health Hospital | Grand Rapids, Michigan 49506 |
University of North Carolina | Chapel Hill, North Carolina 27599 |
Northwestern University | Chicago, Illinois 60611 |
University of Florida | Gainesville, Florida 32610-0277 |
Saint Louis University Hospital | St. Louis, Missouri 63110-0250 |
University of Rochester | Rochester, New York 14642 |
Emory University | Atlanta, Georgia 30322 |
Wayne State University | Detroit, Michigan 48202 |
University of Arizona Health Sciences Center | Tucson, Arizona 85724 |
University of Kentucky | Lexington, Kentucky 40536-0098 |
Wichita CCOP | Wichita, Kansas 67214-3882 |
Montana Cancer Consortium CCOP | Billings, Montana 59101 |
Huntsman Cancer Institute/University of Utah | Salt Lake City, Utah 84112 |
UC Davis Comprehensive Cancer Center | Sacramento, California 95817 |
Tulane University Health Sciences Center | New Orleans, Louisiana 70112 |
Montana Cancer Specialists | Missoula, Montana 59807-7877 |
Florida Hospital | Orlando, Florida 32803 |
University of Chicago Comprehensive Cancer Center | Chicago, Illinois 60637-1470 |
M D Anderson Cancer Center | Houston, Texas 77030 |
Penn State Milton S Hershey Medical Center | Hershey, Pennsylvania 17033 |
Hays Medical Center | Hays, Kansas 67601 |
Froedtert and the Medical College of Wisconsin | Milwaukee, Wisconsin 53226 |
North Shore Hematology Oncology | Libertyville, Illinois 60048 |
Hematology Oncology Associates of Illinois - Skokie | Skokie, Illinois 60076 |
Saint Francis Hospital and Health Centers | Beech Grove, Indiana 46107 |
Fort Wayne Medical Oncology and Hematology Inc - State Boulevard | Fort Wayne, Indiana 46845 |
Reid Hospital and Health Care Services | Richmond, Indiana 47374 |
Mercy Medical Center-Sioux City | Sioux City, Iowa 51104 |
Saint Luke's Regional Medical Center | Sioux City, Iowa 51104 |
Cancer Center of Kansas - El Dorado | El Dorado, Kansas 67042 |
Cancer Center of Kansas-Kingman | Kingman, Kansas 67068 |
Cancer Center of Kansas - Parsons | Parsons, Kansas 67357 |
Cancer Center of Kansas - Pratt | Pratt, Kansas 67124 |
Saint Francis Hospital and Medical Center - Topeka | Topeka, Kansas 66606 |
Cancer Center of Kansas-Wichita Medical Arts Tower | Wichita, Kansas 67208 |
Cancer Center of Kansas - Main Office | Wichita, Kansas 67214 |
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 |
Truman Medical Center | Kansas City, Missouri 64108 |
Hematology-Oncology Centers of the Northern Rockies PC | Billings, Montana 59101 |
Saint Vincent Healthcare | Billings, Montana 59101 |
Billings Clinic | Billings, Montana 59107-7000 |
Saint James Community Hospital and Cancer Treatment Center | Butte, Montana 59701 |
Benefis Healthcare- Sletten Cancer Institute | Great Falls, Montana 59405 |
Saint Peter's Community Hospital | Helena, Montana 59601 |
Glacier Oncology PLLC | Kalispell, Montana 59901 |
Saint Patrick Hospital - Community Hospital | Missoula, Montana 59802 |
Good Samaritan Hospital - Dayton | Dayton, Ohio 45406 |
Dayton CCOP | Dayton, Ohio 45429 |
Samaritan North Health Center | Dayton, Ohio 45415 |
Blanchard Valley Hospital | Findlay, Ohio 45840 |
Atrium Medical Center-Middletown Regional Hospital | Franklin, Ohio 45005-1066 |
Kettering Medical Center | Kettering, Ohio 45429 |
Saint Rita's Medical Center | Lima, Ohio 45801 |
Upper Valley Medical Center | Troy, Ohio 45373 |
Harrison Bremerton Hematology and Oncology | Bremerton, Washington 98310 |
Columbia Basin Hematology and Oncology PLLC | Kennewick, Washington 99336 |
Minor and James Medical PLLC | Seattle, Washington 98104 |
The Polyclinic | Seattle, Washington 98122 |
Swedish Medical Center-First Hill | Seattle, Washington 98122-4307 |
West Virginia University | Morgantown, West Virginia 26506 |
University of Maryland Greenebaum Cancer Center | Baltimore, Maryland 21201 |
Kansas City Cancer Centers - North | Kansas City, Missouri 64154 |
Cancer Center of Kansas-Liberal | Liberal, Kansas 67901 |
University of Michigan University Hospital | Ann Arbor, Michigan 48109 |
Sandra L Maxwell Cancer Center | Cedar City, Utah 84720 |
Intermountain Medical Center | Murray, Utah 84157 |
Utah Valley Regional Medical Center | Provo, Utah 84603 |
Dixie Medical Center Regional Cancer Center | Saint George, Utah 84770 |
Utah Cancer Specialists-Salt Lake City | Salt Lake City, Utah 84106 |
Skagit Valley Hospital | Mt. Vernon, Washington 98273 |
Evergreen Hematology and Oncology PS | Spokane, Washington 99218 |
Kansas City Cancer Centers-Southwest | Overland Park, Kansas 66210 |
Arizona Cancer Center at University Medical Center North | Tucson, Arizona 85719 |
Kansas City Cancer Center-West | Kansas City, Kansas 66112 |
Kansas City Cancer Center-Shawnee Mission | Shawnee Mission, Kansas 66204 |
Kansas City Cancer Center - South | Kansas City, Missouri 64131 |
Kansas City Cancer Center-Lee's Summit | Lee's Summit, Missouri 64064 |
Cancer Care Center at Island Hospital | Anacortes, Washington 98221 |
Highline Medical Center-Main Campus | Burien, Washington 98166 |
United General Hospital | Sedro-Woolley, Washington 98284 |
The Jewish Hospital | Cincinnati, Ohio 45236 |
Stanford University Hospitals and Clinics | Stanford, California 94305 |
Siouxland Hematology Oncology Associates | Sioux City, Iowa 51101 |
Swedish Cancer Institute-Issaquah | Issaquah, Washington 98029 |
Southwest Oncology Group | San Antonio, Texas 78245 |
Southwest Oncology Group (SWOG) Research Base | San Antonio, Texas 78245 |
Via Christi Hospital-Pittsburg | Pittsburg, Kansas 66762 |
PeaceHealth Saint Joseph Medical Center | Bellingham, Washington 98225 |
Illinois Cancer Specialists-Niles | Niles, Illinois 60714 |
Bronson Battle Creek | Battle Creek, Michigan 49017 |
Promise Regional Medical Center-Hutchinson | Hutchinson, Kansas 65702 |
Harrison Poulsbo Hematology and Oncology | Poulsbo, Washington 98370 |
Presence Saint Mary's Hospital | Kankakee, Illinois 60901 |
Hematology/Oncology Clinic LLP | Baton Rouge, Louisiana 70809 |
Swedish Medical Center-Edmonds | Edmonds, Washington 98026 |