Phase II Trial of Induction with L-ASP/CTX/DNM/PRED/VCR Followed by Intensive Consolidation in Adult Patients with Previously Untreated Acute Lymphocytic Leukemia
Basic Trial Information
|Phase II||Treatment||Closed||15 and over||NCI||CLB-8811|
I. Determine, in a group-wide Phase II study, the feasibility and toxicity of an intensive chemotherapy program consisting of induction with L-asparaginase/cyclophosphamide/daunomycin/prednisone/vincristine (L-ASP/CTX/DNM/PRED/VCR) and intensification with cytosine arabinoside/L-ASP/CTX/6-mercaptopurine/VCR in previously untreated patients with acute lymphocytic leukemia. II. Determine the response rate to this induction regimen. III. Investigate the disease-free survival of complete responders who receive intensification and maintenance on protocol. IV. Investigate further the prognostic significance of immunophenotype, cytogenetics, and molecular analysis as well as such patient characteristics on entry as age, WBC and platelet counts, mediastinal mass, organomegaly, and lymphadenopathy. V. Investigate the prognostic significance of the day 7 bone marrow examination.
See General Eligibility Criteria
See General Eligibility Criteria
General Eligibility Criteria:
Patients aged 15 years and older with an unequivocal diagnosis of adult lymphoblastic leukemia (ALL) based on FAB classification (L1-L3), provided they have received no prior treatment other than emergency leukapheresis. Cytochemical and immunologic studies performed at the treating institution must be consistent with the diagnosis. All patients must simultaneously be entered on CLB-8364 (immunology); patients whose marrow is not aspirable on 2 attempts and whose blood does not contain ALL cells remain eligible for this study. Additionally, concurrent registration on CLB-8461 (cytogenetics), CLB-8762 (molecular subtypes in Ph1-positive ALL), and CLB-8763 (Ig and TCR gene rearrangements in ALL) is strongly encouraged. Management throughout the entire duration of protocol treatment must be carried out at a medical facility having ready access to blood product support and adequately staffed to care for the severely neutropenic patient with multiple therapy-induced toxicities. Adequate hepatic and renal function must be documented by the following laboratory parameters, unless abnormalities are directly attributable to leukemia: total bilirubin less than 1.5 times normal, alkaline phosphatase and SGOT/SGPT each less than twice normal, and serum creatinine less than 1.5 times normal (biopsies of liver or kidney are not required to document leukemic involvement). There may be no previous or concomitant other malignancy except for curatively treated carcinoma in situ of the cervix or basal cell carcinoma of the skin. Patients must be free from other serious medical illness that would limit survival to less than 2 years and any psychiatric condition that would prevent informed consent. Specifically, there must be no uncontrolled or severe cardiovascular disease, including myocardial infarction within 6 months and CHF; any viral, bacterial, or fungal infection and active duodenal ulcer must be controlled prior to entry.
Approximately 112 patients will be entered over 18 months.
Nonrandomized study. Patients who have testicular leukemia on admission and those who develop testicular involvement subsequently are treated according to Regimen A. Patients who have CNS leukemia on entry or develop CNS disease subsequently are treated according to Regimen B. Induction: 5-Drug Combination Chemotherapy. Cyclophosphamide, CTX, NSC-26271; Daunorubicin, Daunomycin, DNM, NSC-82151; Vincristine, VCR, NSC-67574; Prednisone, PRED, NSC-10023; L-Asparaginase, L-ASP, NSC-109229. Intensification: 5-Drug Combination Systemic Chemotherapy plus 2-Drug Combination Intrathecal Chemotherapy. CTX; Cytarabine, Cytosine arabinoside, ARA-C, NSC-63878; 6-Mercaptopurine, 6-MP, NSC-755; VCR; L-ASP; plus Intrathecal Methotrexate, IT MTX, NSC-740; Intrathecal Hydrocortisone, IT HC, NSC-10483. CNS Prophylaxis/Interim Maintenance: 2-Drug Combination Systemic Chemotherapy plus Single-agent Intrathecal Chemotherapy plus Radiotherapy. MTX; 6-MP; plus IT MTX; plus whole-brain irradiation using Co60 equipment or linear accelerators with beam energies of 4-6 MeV. Late Intensification: 6-Drug Combination Chemotherapy. Doxorubicin, Adriamycin, ADR, NSC-123127; VCR; Dexamethasone, DM, NSC-34521; CTX; ARA-C; 6-Thioguanine, TG, NSC-752. Maintenance: 4-Drug Combination Chemotherapy. 6-MP; MTX; VCR; PRED. Regimen A: Radiotherapy. Bilateral testicular irradiation using Co60 equipment or linear accelerators with beam energies of 4-6 MeV. Regimen B: Single-agent Intrathecal Chemotherapy plus Radiotherapy. IT MTX; plus whole-brain irradiation using Co60 equipment or linear accelerators with beam energies of 4-6 MeV.
Larson RA, Dodge RK, Burns CP, et al.: A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811. Blood 85 (8): 2025-37, 1995.[PUBMED Abstract]
Wetzler M, Dodge RK, Mrózek K, et al.: Prospective karyotype analysis in adult acute lymphoblastic leukemia: the cancer and leukemia Group B experience. Blood 93 (11): 3983-93, 1999.[PUBMED Abstract]
Trial Contact Information
Trial Lead Organizations
Cancer and Leukemia Group B
Ph: 773-702-6783; 888-824-0200
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.