Phase III Randomized Trial of G-CSF vs Placebo During Induction and Consolidation Chemotherapy for Adult ALL (Summary Last Modified 09/91)
Basic Trial Information
|Phase III||Treatment||Closed||15 and over||NCI||CLB-9111|
I. Compare time to bone marrow recovery, incidence of infection, days of hospitalization, and tolerance of nonhematopoietic organs following intensive chemotherapy for ALL in patients randomized to receive granulocyte colony stimulating factor (G-CSF) vs. placebo. II. Determine the effect of G-CSF on the rate and duration of CR and on the incidence of death during neutropenia in patients treated with the current CALGB intensive 5-drug induction regimen and intensive consolidation program (protocol CLB-8811). III. Compare the dose intensity of chemotherapy that can be delivered to patients receiving G-CSF vs. placebo during the first 3 months of treatment. IV. Continue to investigate the prognostic signifigance for survival of the following disease and patient characteristics: immunophenotype, especially My+ antigens; cytogenetics, especially Ph1, T(8;14), and t(4;11); molecular analyses; entry age; leukocyte and platelet counts; and mediastinal mass, organomegaly, and lymphadenopathy. V. Continue to examine the prognostic significance of the day 7 bone marrow examination.
Unequivocal diagnosis of ALL, FAB classification L1-L3 Cytochemical/immunological studies must be consistent with diagnosis of ALL Patients with acute undifferentiated leukemia with negative myeloperoxidase or Sudan black reactivity and lacking myeloid antigens are also eligible Simultaneous entry on CLB-8364 (immunology) required; patient remains eligible for CLB-9111 even if bone marrow samples are inadequate for CLB-8364 Entry on CLB-8461 (cytogenetics), CLB-8762 (molecular subtypes in Ph1+ ALL), and CLB-8763 (Ig and TCR gene rearrangements in ALL) is strongly encouraged
Biologic therapy: No prior treatment, including hematopoietic growth factors Chemotherapy: No prior treatment except emergency hydroxyurea for up to 72 hours for rapidly progressive hyperleukocytosis Endocrine therapy: No prior treatment Radiotherapy: No prior treatment except a single dose of radiation for CNS leukocytosis Surgery: No prior treatment
Age: 15 years and older Performance status: Not specified Life expectancy: At least 2 years (aside from malignancy) Hematopoietic: Confirmed diagnosis of ALL or AUL Hepatic: Total bilirubin less than 1.5 x normal Renal: Creatinine less than 1.5 x normal Cardiovascular: No MI within 6 months No CHF No other uncontrolled or severe cardiovascular disease Other: No active uncontrolled bacterial, viral, or fungal infection or active duodenal ulcer until such conditions are corrected or controlled No other serious medical condition that would limit survival to less than 2 years No psychiatric condition that would interfere with informed consent or protocol compliance No second malignancy within the past 5 years except: Curatively treated in situ cervical cancer Basal cell skin cancer Management throughout entire duration of protocol treatment must be effected at a facility with ready access to blood product support and adequately staffed to care for severe neutropenia and other severe toxicities
150 patients will be randomized over about 2 years.
Randomized, double-blind study. Following Induction, the study is unblinded; Arm I Induction patients continue to receive G-CSF during Intensification, while Arm II Induction patients do not continue to receive placebo. Otherwise, treatment of medullary disease is the same for all patients following Induction. Gonadal irradiation for patients who develop testicular ALL during remission (on or off protocol therapy) is described under Regimen A; patients with testicular ALL at presentation begin treatment on Regimen A if their gonadal disease persists or worsens at the end of Induction. Treatment of CNS leukemia is described under Regimen B. Induction: Arm I: 5-Drug Combination Chemotherapy plus Hematopoietic Growth Factor Therapy. Cyclophosphamide, CTX, NSC-26271; Daunorubicin, DNR, NSC-82151; Vincristine, VCR, NSC-67574; Prednisone, PRED, NSC-10023; Asparaginase, ASP, NSC-109229; plus Granulocyte Colony Stimulating Factor (Amgen), G-CSF, NSC-614629. Arm II: 5-Drug Combination Chemotherapy plus Placebo. CTX; DNR; VCR; PRED; ASP; plus Placebo. Intensification: 5-Drug Combination Systemic Chemotherapy plus (Arm I Induction patients only) Hematopoietic Growth Factor Therapy plus Single-agent Intrathecal Chemotherapy. CTX; Cytarabine, ARA-C, NSC-63878; Mercaptopurine, MP, NSC-755; VCR; ASP; plus (Arm I Induction patients only) G-CSF; plus Intrathecal Methotrexate, IT MTX, NSC-740. Interim Maintenance/CNS Prophylaxis: 2-Drug Combination Systemic Chemotherapy plus Single-agent Intrathecal Chemotherapy plus Radiotherapy. MP; MTX; plus IT MTX; plus whole-brain irradiation using Co60 equipment or photons with energies of 4-6 MeV. Late Intensification: 6-Drug Combination Chemotherapy. Doxorubicin, DOX, NSC-123127; VCR; CTX; Dexamethasone, DM, NSC-34521; ARA-C; Thioguanine, TG, NSC-752. Maintenance: 4-Drug Combination Chemotherapy. MP; MTX; VCR; PRED. Regimen A (Treatment of Gonadal Disease): Radiotherapy. Bilateral testicular irradiation using Co60 or x-rays with energies of 4-6 MeV. Regimen B (Treatment of CNS Disease): Radiotherapy plus Single-agent Intrathecal Chemotherapy with Leucovorin Rescue. Whole-brain irradiation using Co60 or photons with energies of 4-6 MeV; plus IT MTX; with Leucovorin calcium, CF, NSC-3590.
Larson RA, Linker CA, Dodge RK, et al.: Granulocyte-colony stimulating factor (filgrastim; G-CSF) reduces the time to neutrophil recovery in adults with acute lymphoblastic leukemia receiving intensive remission induction chemotherapy: Cancer and Leukemia Group B study 9111. [Abstract] Proceedings of the American Society of Clinical Oncology 13: A-995, 305, 1994.
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.