Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
| Phase | Type | Status | Age | Sponsor | Protocol IDs |
|---|---|---|---|---|---|
| Phase III | Treatment | Completed | 1 day to 18 years | NCI | DFCI-87001 NCI-T87-0107D, T87-0107 |
Objectives
I. Compare, in a randomized Phase III study, the anti-leukemic efficacy, acute toxicity, and biochemical pharmacology of E. coli, Erwinia, and PEG-modified L-asparaginase administered on day 1 of a 4-day "investigational window" period at the outset of induction chemotherapy in children with previously untreated ALL or AUL (study closed to leukemia patients as of 8/91). II. Determine whether there is any difference in event-free survival and leukemia-free survival among patients treated early in their therapeutic regimen with standard-dose methotrexate vs. high-dose methotrexate with citrovorum rescue (study closed to leukemia patients as of 8/91). III. Compare the control of CNS leukemia and therapy-related toxicity of high-risk and very-high-risk patients randomized to one of the following two regimens of CNS prophylaxis: conventionally fractionated radiotherapy vs. hyperfractionated irradiation, each of which is administered with concomitant intrathecal methotrexate/cytosine arabinoside (study closed to leukemia patients as of 8/91).
Entry Criteria
Disease Characteristics:
See General Eligibility Criteria
Patient Characteristics:
See General Eligibility Criteria
General Eligibility Criteria:
Previously untreated patients aged 1 day to 18 years with a diagnosis of ALL, AUL, or Murphy's Stage III/IV lymphoblastic lymphoma; as of 8/91, the study is closed to patients with acute leukemia but remains open to those with lymphoblastic lymphoma. Those patients found to have mature B-cell ALL, as indicated by surface immunoglobulin and/or translocation t8,14, will be removed from study. Patients with presumptive systemic infection are eligible for initiation of chemotherapy as soon as appropriate diagnostic studies have been completed and antimicrobial therapy started. The following patients are excluded from investigational window treatment and start formal Induction chemotherapy immediately: those who are gravely ill (specifically, those with severe respiratory distress, those requiring endotracheal intubation, those with septic shock, and those who have had intracranial hemorrhage); and those who at diagnosis or after appropriate hydration and supportive care demonstrate evidence of severe hepatic or pancreatic dysfunction (bilirubin greater than 3.0 mg/dl, PT and/or PTT more than twice the control levels; or serum amylase more than twice normal).
Expected Enrollment
It is anticipated that a total accrual of 350 patients within 4 years will be sufficient for the study.
Outline
Randomized study (randomized portion closed as of 8/91). Patients with Murphy's Stage III/IV lymphoblastic lymphoma are nonrandomly assigned to Regimen D. All eligible patients with ALL or AUL were initially randomized on Arms I, II, and III for treatment during the Investigational Window. Subsequent treatment for these patients was based on prognostic risk. Standard-risk patients satisfied all of the following criteria: WBC less than 20,000; age 24 months 1 day to 8 years 11 months; no CNS disease or mediastinal mass; absence of T-cell markers; remission induction within 33 days; Philadelphia chromosome (+9;22)-negative; no evidence of biphenotypic leukemia. High-risk patients demonstrated any or all of the following: WBC 20,001-100,000; age 366 days to 24 months or over 9 years; CNS disease present; mediastinal mass present; T-cell markers present; remission induction longer than 33 days; evidence of biphenotypic leukemia. Very-high-risk patients were those with a WBC greater than 100,000 and/or age under 365 days and Philadelphia chromosome-positive. Patients of all risk strata were randomized to standard-dose vs. high-dose methotrexate during Induction (patients who received high-dose MTX were screened for "third space" fluid accumulation, mucositis, or severe skin rash, and met the following laboratory requirements: bilirubin less than 1.2 mg/dl; and serum creatinine less than 0.6, less than 0.8, less than 1.0, and less than 1.2 mg/dl for patients aged 0-5, 6-10, 10-15, and over 15 years, respectively). Patients with Down's syndrome were not eligible for high-dose methotrexate and received the lower dose. High-risk and very-high-risk patients were randomized to standard fractionation vs. hyperfractionation of craniocervical irradiation during CNS Prophylaxis except for patients treated at institutions that are unable to give ketamine twice a day were assigned to conventional fractionation. Investigational Window (Arms closed as of 8/91). Arm I: Single-agent Chemotherapy. E. coli L-Asparaginase, L-ASP, NSC-109229. Arm II: Single-agent Chemotherapy. Erwinia L-ASP, NSC-106977. Arm III: Single-agent Chemotherapy. PEG-modified L-ASP. Regimen A (Standard-Risk Patients)(Regimen closed as of 8/91). Induction: 4-Drug Combination Systemic Chemotherapy with Leukovorin Rescue (only for patients receiving high-dose MTX) plus Single-agent Intrathecal Chemotherapy. Vincristine, VCR, NSC-67574; Prednisone, PRED, NSC-10023; Methotrexate (Standard Dose or High Dose, depending on randomization), MTX, NSC-740; Adriamycin, ADR, NSC-123127; with Citrovorum Factor, CF, NSC-3590; plus Intrathecal Cytosine arabinoside, IT ARA-C, NSC-63878. CNS Prophylaxis and Continuation: 5-Drug Combination Systemic Chemotherapy plus 2-Drug Combination Intrathecal Chemotherapy plus Bactrim Prophylaxis. VCR; PRED; 6-Mercaptopurine, 6-MP, NSC-755; E. coli L-ASP, NSC-109229; MTX; plus IT MTX; IT ARA-C; plus Bactrim. Regimen B (High-Risk Patients)(Regimen closed as of 8/91). Induction: 4-Drug Combination Systemic Chemotherapy with Leukovorin Rescue (only for patients receiving high-dose MTX) plus Single-agent Intrathecal Chemotherapy. VCR; PRED; MTX (Standard Dose or High Dose, depending on randomization); ADR; with CF; plus IT ARA-C. CNS Prophylaxis and Continuation: 6-Drug Combination Systemic Chemotherapy plus 2-Drug Combination Intrathecal Chemotherapy plus Radiotherapy plus Bactrim Prophylaxis. VCR; PRED; E. coli L-ASP; ADR; 6-MP; MTX; plus IT MTX; IT ARA-C; plus craniospinal irradiation using linear accelerators of 4 or 6 MeV; plus Bactrim. Regimen C (Very-High-Risk Patients)(Regimen closed as of 8/91). Induction: 4-Drug Combination Systemic Chemotherapy with Leukovorin Rescue (only for patients receiving high-dose MTX) plus Single-agent Intrathecal Chemotherapy. VCR; PRED; MTX (Standard Dose or High Dose, depending on randomization); ADR; with CF; plus IT ARA-C. Intensification: 5-Drug Combination Systemic Chemotherapy with Leukovorin Rescue plus Single-agent Intrathecal Chemotherapy. VCR; E. coli L-ASP; 6-MP; High-Dose MTX; High-Dose ARA-C; with CF; plus IT MTX. CNS Prophylaxis and Continuation: 6-Drug Combination Systemic Chemotherapy plus 2-Drug Combination Intrathecal Chemotherapy plus Radiotherapy plus Bactrim Prophylaxis. VCR; PRED; E. coli L-ASP; ADR; 6-MP; MTX; plus IT MTX; IT ARA-C; plus craniospinal irradiation (delivered by conventional fractionation vs. hyperfractionation according to randomization) using linear accelerators of 4 or 6 MeV; plus Bactrim. Regimen D (Lymphoblastic Lymphoma Patients). Induction: 4-Drug Combination Systemic Chemotherapy plus Single-agent Intrathecal Chemotherapy. VCR; PRED; MTX; ADR; plus IT ARA-C. CNS Prophylaxis and Continuation: 6-Drug Combination Systemic Chemotherapy plus 2-Drug Combination Intrathecal Chemotherapy plus Radiotherapy plus Bactrim Prophylaxis. VCR; PRED; E. coli L-ASP; ADR; 6-MP; MTX; plus IT MTX; IT ARA-C; plus craniospinal irradiation using linear accelerators of 4 or 6 MeV; plus Bactrim.Published Results
LeClerc JM, Billett AL, Gelber RD, et al.: Treatment of childhood acute lymphoblastic leukemia: results of Dana-Farber ALL Consortium Protocol 87-01. J Clin Oncol 20 (1): 237-46, 2002.[PUBMED Abstract]
Waber DP, Tarbell NJ, Fairclough D, et al.: Cognitive sequelae of treatment in childhood acute lymphoblastic leukemia: cranial radiation requires an accomplice. J Clin Oncol 13 (10): 2490-6, 1995.[PUBMED Abstract]
Related PublicationsSilverman LB, Stevenson KE, O'Brien JE, et al.: Long-term results of Dana-Farber Cancer Institute ALL Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1985-2000). Leukemia 24 (2): 320-34, 2010.[PUBMED Abstract]
Waber DP, Silverman LB, Catania L, et al.: Outcomes of a randomized trial of hyperfractionated cranial radiation therapy for treatment of high-risk acute lymphoblastic leukemia: therapeutic efficacy and neurotoxicity. J Clin Oncol 22 (13): 2701-7, 2004.[PUBMED Abstract]
Silverman LB, Declerck L, Gelber RD, et al.: Results of Dana-Farber Cancer Institute Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1981-1995). Leukemia 14 (12): 2247-56, 2000.[PUBMED Abstract]
Trial Lead Organizations
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
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| Stephen Sallan, MD, Protocol chair | |
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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.
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