Phase II Study in Adults With Untreated Acute Lymphoblastic Leukemia Testing Increased Doses of Daunorubicin During Induction, and Cytarabine During Consolidation, Followed by High-Dose Methotrexate and Intrathecal Methotrexate in Place of Cranial Irradiation
- Determine the complete response rate and toxicity of escalating doses of daunorubicin
in patients under 60 years old with untreated acute lymphoblastic leukemia (ALL).
- Determine the complete response rate and toxicity of a constant dose of daunorubicin in
patients at least 60 years old with untreated ALL.
- Determine the toxicity of high dose cytarabine during postremission therapy in these
- Determine the CNS relapse rate of ALL when prophylactic intrathecal methotrexate and
high-dose intravenous chemotherapy replace cranial irradiation.
- Course I: Patients are assigned to 1 of 2 induction treatment groups based on age.
- Group 1 (under age 60): Patients receive cyclophosphamide IV over 15-30 minutes on
day 1, escalating doses of daunorubicin IV over 5-10 minutes on days 1-3,
vincristine IV on days 1, 8, 15, and 22, oral prednisone on days 1-21,
asparaginase intramuscularly on days 5, 8, 11, 15, 18, and 22, and filgrastim
(G-CSF) subcutaneously (SC) beginning on day 4 and continuing for at least 7 days
and then until blood counts recover.
- Group 2 (age 60 and over): Patients receive vincristine, asparaginase,
cyclophosphamide, and G-CSF as in group 1, fixed dose daunorubicin IV over 5-10
minutes on days 1-3, and oral prednisone on days 1-7.
Patients are then evaluated for bone marrow cellularity on day 29. Those with M0, M1, or M2
cellularity proceed to course II. Patients with M3 cellularity may proceed to course II or
be removed from study.
- Course II (early intensification): Patients receive intrathecal methotrexate and
cyclophosphamide IV over 15-30 minutes on day 1, cytarabine IV over 3 hours on days
1-3, and G-CSF SC beginning on day 4.
Bone marrow is again examined on day 29. Patients with M0 or M1 cellularity after course I
and no sign of relapse after course II proceed to course III. Patients with M2 or M3
cellularity after course I must have M0 or M1 cellularity after course II to proceed to
course III. Patients with M2 or M3 cellularity after course II are removed from study.
- Course III: Patients receive intrathecal methotrexate, vincristine IV, and methotrexate
IV over 3 hours on days 1, 8, and 15 and oral methotrexate every 6 hours for 4 doses
beginning 6 hours after starting methotrexate IV on days 1, 2, 8, 9, 15, and 16.
Patients receive leucovorin calcium IV 6 hours after the last oral methotrexate dose on
days 2, 9, and 16 and oral leucovorin calcium beginning 12 hours after leucovorin
calcium IV for at least 4 doses on days 3, 4, 10, 11, 17, and 18.
Patients must be off leucovorin calcium for a minimum of 3 days before beginning days 8 and
15 of treatment. Patients who maintain M0 or M1 cellularity on day 29 of course III continue
therapy. Those with M2 or M3 cellularity after course III are removed from the study.
- Course IV (Late intensification): Repeat course I.
- Course V (Late intensification): Repeat course II.
- Course VI (CNS intensification): Repeat course III.
- Course VII (Prolonged maintenance): Patients receive oral mercaptopurine daily,
vincristine IV once every 4 weeks, oral prednisone on days 1-5, and oral methotrexate
on days 1, 8, 15, and 22. Courses repeat every 4 weeks for up to 18 months.
Patients with testicular disease receive gonadal radiotherapy anytime after course I.
Chemotherapy is not halted during radiotherapy.
Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then
annually for 10 years.
PROJECTED ACCRUAL: A total of 140 patients will be accrued for this study within 15 months.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
6 months post treatment
Wendy Stock, MD
University of Chicago
United States: Federal Government
|Roswell Park Cancer Institute||Buffalo, New York 14263|
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|
|Walter Reed Army Medical Center||Washington, District of Columbia 20307-5000|
|University of Chicago Cancer Research Center||Chicago, Illinois 60637|
|University of Iowa Hospitals and Clinics||Iowa City, Iowa 52242|
|University of Massachusetts Memorial Medical Center||Worcester, Massachusetts 01655|
|Lineberger Comprehensive Cancer Center, UNC||Chapel Hill, North Carolina 27599-7295|
|Duke Comprehensive Cancer Center||Durham, North Carolina 27710|
|Comprehensive Cancer Center of Wake Forest University Baptist Medical Center||Winston-Salem, North Carolina 27157-1082|
|Arthur G. James Cancer Hospital - Ohio State University||Columbus, Ohio 43210|
|Medical University of South Carolina||Charleston, South Carolina 29425-0721|
|Rhode Island Hospital||Providence, Rhode Island 02903|
|Vermont Cancer Center||Burlington, Vermont 05401-3498|
|CCOP - Southern Nevada Cancer Research Foundation||Las Vegas, Nevada 89106|
|University of California San Diego Cancer Center||La Jolla, California 92093-0658|
|UCSF Cancer Center and Cancer Research Institute||San Francisco, California 94115-0128|
|CCOP - Christiana Care Health Services||Wilmington, Delaware 19899|
|CCOP - Mount Sinai Medical Center||Miami Beach, Florida 33140|
|Marlene & Stewart Greenebaum Cancer Center, University of Maryland||Baltimore, Maryland 21201|
|Ellis Fischel Cancer Center - Columbia||Columbia, Missouri 65203|
|Barnes-Jewish Hospital||Saint Louis, Missouri 63110|
|Norris Cotton Cancer Center||Lebanon, New Hampshire 03756|
|CCOP - North Shore University Hospital||Manhasset, New York 11030|
|State University of New York - Upstate Medical University||Syracuse, New York 13210|
|CCOP - Southeast Cancer Control Consortium||Winston-Salem, North Carolina 27104-4241|
|University of Tennessee, Memphis Cancer Center||Memphis, Tennessee 38103|
|MBCCOP - Massey Cancer Center||Richmond, Virginia 23298-0037|
|Mount Sinai Medical Center, NY||New York, New York 10029|
|New York Presbyterian Hospital - Cornell Campus||New York, New York 10021|
|Veterans Affairs Medical Center - Birmingham||Birmingham, Alabama 35233|
|Veterans Affairs Medical Center - White River Junction||White River Junction, Vermont 05009|
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|Lombardi Cancer Center, Georgetown University||Washington, District of Columbia 20007|
|St. Barnabas Medical Center||Livingston, New Jersey 07039|
|North Shore University Hospital||Manhasset, New York 11030|
|Veterans Affairs Medical Center - Chicago (Westside Hospital)||Chicago, Illinois 60612|
|Veterans Affairs Medical Center - San Francisco||San Francisco, California 94121|
|CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.||Syracuse, New York 13217|
|Veterans Affairs Medical Center - Memphis||Memphis, Tennessee 38104|
|Veterans Affairs Medical Center - Richmond||Richmond, Virginia 23249|
|University of Illinois at Chicago Health Sciences Center||Chicago, Illinois 60612|
|Veterans Affairs Medical Center - Togus||Togus, Maine 04330|
|Veterans Affairs Medical Center - Minneapolis||Minneapolis, Minnesota 55417|
|Veterans Affairs Medical Center - Columbia (Truman Memorial)||Columbia, Missouri 65201|
|University of Nebraska Medical Center||Omaha, Nebraska 68198-3330|
|Veterans Affairs Medical Center - Buffalo||Buffalo, New York 14215|
|Veterans Affairs Medical Center - Syracuse||Syracuse, New York 13210|
|Veterans Affairs Medical Center - Durham||Durham, North Carolina 27705|
|St. Joseph's Hospital and Medical Center||Paterson, New Jersey 07503|
|Cooper Cancer Institute||Camden, New Jersey 08103|