RATIONALE: Biological therapy using growth factors may be effective in reducing side effects
in patients who have hematologic cancer and are receiving radiation therapy, chemotherapy,
and peripheral stem cell transplantation.
PURPOSE: Randomized phase II trial to study the effectiveness of biological therapy to
reduce side effects in patients who are undergoing radiation therapy, chemotherapy, and
peripheral stem cell transplantation in treating lymphoma or leukemia.
OBJECTIVES: I. Determine the efficacy of recombinant human keratinocyte growth factor
(rHuKGF) in reducing severe oral mucositis induced by total body irradiation and high dose
chemotherapy in patients with hematologic malignancies. II. Compare the incidence of severe
oral mucositis, the use of transdermal or perenteral opioid analgesics, and the incidence
and duration of grade 2-4 diarrhea with or without rHuKGF in these patients. III. Determine
the quality of life of these patients. IV. Determine the duration of febrile neutropenia and
the duration of treatment with intravenous antifungals or antibiotics in these patients.
OUTLINE: This is a randomized, double blind, placebo controlled, multicenter study. Patients
are stratified according to center. Patients are randomized to one of three treatment arms.
Arm I: Patients receive recombinant human keratinocyte growth factor (rHuKGF) IV on days -11
to -9, -5, and 0 to 2. Total body irradiation (TBI) is administered twice a day on days -8
to -5. Patients receive etoposide IV over 4 hours on day -4 and cyclophosphamide IV over 1
hour on day -2 (some patients may receive an alternate regimen of ifosfamide IV over 1 hour
on days-4 to 0 followed each day by etoposide IV over 23 hours). Filgrastim (G-CSF) is
administered subcutaneously (SQ) beginning on day 0 and continuing for up to 21 days until
blood counts recover. Autologous peripheral blood stem cells (PBSC) are infused on day 0.
Arm II: Patients receive rHuKGF on days -11 to -9 and -5 as in arm I. Placebo is
administered on days 0 to 2. TBI, chemotherapy, and PBSC transplantation are administered as
in arm I. Arm III: Patients receive placebo on days -11 to -9, -5, and 0 to 2. TBI,
chemotherapy, and PBSC transplantation are administered as in arm I. Quality of life is
assessed prior to treatment, daily during therapy and until day 28 after transplantation.
Patients are followed at day 28 and approximately day 60-100.
PROJECTED ACCRUAL: At least 111 patients (37 per arm) will be accrued for this study within
DISEASE CHARACTERISTICS: Diagnosis of one of the following: Non-Hodgkin's lymphoma
Hodgkin's disease Acute myelogenous leukemia Acute lymphoblastic leukemia Chronic
myelogenous leukemia Chronic lymphocytic leukemia Eligible for fractionated total body
irradiation plus high dose chemotherapy followed by autologous peripheral blood stem cell
support No prior entry into this study
PATIENT CHARACTERISTICS: Age: 18 to 65 Performance status: Karnofsky 70-100% SWOG 0 or 1
Life expectancy: Not specified Hematopoietic: Absolute neutrophil count greater than
1,000/mm3 Platelet count greater than 100,000/mm3 Hepatic: Bilirubin no greater than 2
mg/dL Renal: Creatinine no greater than 2 mg/dL Cardiovascular: No New York Heart
Association class III or IV heart disease Pulmonary: DLCO at least 60% predicted Other: No
other prior or concurrent malignancy No active infection or oral mucositis No diabetes
mellitus requiring insulin HIV negative No sensitivity to E. coli derived products Not
pregnant or nursing Negative pregnancy test Fertile patients must use effective
PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics No prior bone
marrow or peripheral blood stem cell transplantation No concurrent interleukin-11
Chemotherapy: See Disease Characteristics No other concurrent chemotherapy Endocrine
therapy: Not specified Radiotherapy: See Disease Characteristics No prior extensive
radiotherapy that would preclude study irradiation Surgery: Not specified Other: At least
30 days since prior investigational study No other concurrent investigational agents No
concurrent prophylactic oral cryotherapy during study chemotherapy