PILOT MULTINATIONAL PROTOCOLS IN ACUTE LYMPHOBLASTIC LEUKEMIA AND DIFFUSE NON-HODGKIN'S LYMPHOMA
- Provide a standard protocol for specific therapy that is relatively easy to administer
and relatively inexpensive but conforms to modern treatment principles, and determine
whether such therapy can be administered safely and effectively in patients with acute
lymphoblastic lymphoma or diffuse non-Hodgkin's lymphoma who live in developing
- Determine the rates of relapse and survival in patients treated with these protocols,
and relate this data to disease subtype and clinical presentation in order to obtain a
database on which to build future stratagems.
OUTLINE: This is a multicenter study.
Patients with acute lymphoblastic leukemia or lymphoblastic lymphoma with any degree of bone
marrow involvement are assigned to Protocol MCP-841. Patients with mediastinal or localized
lymphoblastic lymphoma (a single nodal or extranodal site) without bone marrow involvement,
or other types of diffuse non-Hodgkin's lymphoma with or without bone marrow involvement are
assigned to Protocol MCP-842.
- First induction therapy: Patients receive daunorubicin (DNR) IV on days 8, 15, and 29;
vincristine (VCR) IV on days 1, 8, 15, 22, and 29; asparaginase (ASP) intramuscularly
(IM) every other day on days 2-20; oral prednisone (PRED) on days 1-28; and
methotrexate (MTX) intrathecally (IT) on days 1, 8, 15, and 22. Second induction
therapy: Patients receive oral mercaptopurine (MP) on days 1-7 and 15-21;
cyclophosphamide (CTX) IV over 30 minutes on days 1 and 15; MTX IT as in first
induction therapy; and cranial irradiation on days 4-14.
- Alternative to second induction (if a cranial irradiation facility is unavailable):
Patients receive MP and CTX as in second induction therapy; cytarabine (ARA-C) IV every
12 hours on days 1, 2, 15, 16, 29, and 30; and MTX IT on days 8 and 22.
Patients with low-risk disease (WBC no greater than 10,000/mm3, age 3 to 6 years, no
prominent lymphadenopathy (less than 3 cm in diameter in each nodal region), normal CSF, no
mediastinal mass, no enlargement of liver or spleen, and no cranial nerve palsies) proceed
directly to maintenance therapy. All other patients are considered high risk, and they
repeat first induction therapy and then proceed to consolidation therapy.
- Consolidation therapy: Patients receive MP and CTX as in second induction therapy, VCR
IV on days 1 and 15, and ARA-C subcutaneously (SC) every 12 hours on days 1-3 and
- Maintenance therapy: Patients receive VCR IV on day 1; DNR IV on day 1; oral PRED on
days 1-7; ASP IM on days 1, 3, 5, and 7; and oral MTX once weekly and oral MP daily on
days 15-35, 43-63, and 71-91. Maintenance therapy continues for a total of 6 courses.
- Patients undergo surgical resection of intra-abdominal masses, if feasible. Patients
with low-risk disease (completely resected tumor or a single extra-abdominal site of
involvement (other than the mediastinum), but without lymphoblastic lymphoma) are
assigned to treatment group 2. All other patients, including those with lymphoblastic
lymphoma without bone marrow involvement, are considered high risk and they are
assigned to treatment group 1.
- Group 1 (high risk): Patients receive one course of regimen A comprising CTX IV over 15
minutes on days 1-4; VCR IV on days 1, 8, and 15; doxorubicin (DOX) IV on days 1 and 2;
ARA-C IV over 3 hours every 12 hours on day 1; ARA-C IT on day 4; and MTX IT on days 8
and 12. Patients then receive one course of regimen B comprising ifosfamide IV over 30
minutes on days 1-5, etoposide IV over 1 hour and MTX IV on days 1-3, VCR IV on day 8,
ARA-C IT on days 1 and 4, and MTX IT as in regimen A. Patients then receive a second
course of regimen A, followed by a second course of regimen B.
- Group 2 (low risk): Patients receive one course of regimen A, followed by one course of
regimen B, and then a second course of regimen A. DOX is withheld during both courses
of regimen A. IT therapy is withheld during the second course of regimen A.
Patients are followed every 2 months for 1 year (Protocol MCP-841) or at 1, 2, 3, 4, 6, and
8 months (Protocol MCP-842), every 6 months for 5 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 4,000 patients will be accrued for this study.
Primary Purpose: Treatment
Ian Trevor Magrath, MD, FRCP, FRCPath
National Cancer Institute (NCI)
United States: Federal Government
|Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support||Bethesda, Maryland 20892-1182|