RATIONALE: Keratinocyte growth factor may prevent symptoms of mucositis in patients
receiving radiation therapy and chemotherapy.
PURPOSE: Randomized phase II trial to study the effectiveness of keratinocyte growth factor
in preventing oral mucositis in patients who have hematologic cancers and who are undergoing
radiation therapy and chemotherapy before autologous peripheral stem cell transplantation.
OBJECTIVES: I. Determine the efficacy of recombinant keratinocyte growth factor in reducing
the duration of severe oral mucositis induced by total body irradiation and high dose
chemotherapy in patients with hematologic malignancies. II. Determine the incidence and
duration of severe oral mucositis, grade 2-4 diarrhea, and febrile neutropenia in these
patients. III. Determine the necessity of use of transdermal or parenteral opioid analgesics
and IV antifungals or antibiotics for febrile neutropenia or infections in these patients.
IV. Determine the quality of life of these patients.
OUTLINE: This is a randomized, double blind, placebo controlled, multicenter study. Patients
are stratified by center. Patients are randomized to one of three treatment arms. Arm I:
Patients receive 7 doses of recombinant human keratinocyte growth factor (rHuKGF). Arm II:
Patients receive 4 doses of rHuKGF followed by 3 doses of placebo. Arm III: Patients receive
7 doses of placebo. Patients receive one of two conditioning regimens. Primary conditioning
regimen: Patients receive rHuKGF or placebo daily on days -11, -10, -9, -5, 0, 1, and 2.
Total body irradiation (TBI) is administered twice a day on days -8 to -5. Patients receive
etoposide on day -4, cyclophosphamide IV over 1 hour on day -2, and peripheral blood stem
cell transplantation (PBSCT) on day 0. Filgrastim (G-CSF) IV or SC is administered beginning
on day 0 and continuing for 21 days or until blood counts recover. Secondary conditioning
regimen: Patients receive rHuKGF or placebo daily on days -13, -12, -11, -7, 0, 1, and 2.
TBI is administered twice a day on days -10 to -7. Patients receive ifosfamide IV over 1
hour followed by etoposide over 23 hours on days -6 to -2, then PBSCT on day 0. G-CSF IV or
SC is administered beginning on day 0 for 21 days or until blood counts recover. Quality of
life is assessed daily beginning on day -11 and continuing until day 28. Patients are
followed at day 28 and then at day 60-100.
PROJECTED ACCRUAL: A minimum of 111 patients (37 per arm) will be accrued for this study.
DISEASE CHARACTERISTICS: Diagnosis of Non-Hodgkin's lymphoma, Hodgkin's disease, acute
myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, chronic
lymphocytic leukemia, or multiple myeloma Eligible for total body irradiation plus high
dose chemotherapy followed by autologous peripheral blood stem cell transplantation At
least 1,500,000 CD34+ cells/kg cryopreserved No prior treatment on this study
PATIENT CHARACTERISTICS: Age: 12 to 65 Performance status: Karnofsky 70-100% SWOG 0 or 1
Life expectancy: Not specified Hematopoietic: Absolute neutrophil count greater than
1000/mm3 Platelet count greater than 100,000/mm3 If conditioning regimen scheduled soon
after apheresis, platelet count of greater than 50,000/mm3 but less than 100,000/mm3
allowed Hepatic: Bilirubin no greater than 2 mg/dL Renal: Creatinine no greater than 2
mg/dL Cardiovascular: No congestive heart failure No New York Heart Association class III
or IV heart disease Pulmonary: DLCO at least 50% predicted Other: No prior or concurrent
second malignancy No active infection or oral mucositis No insulin dependent diabetes
mellitus HIV negative No sensitivity to E. coli derived products Not pregnant or nursing
Fertile patients must use effective contraception one month before, during, and one month
PRIOR CONCURRENT THERAPY: Biologic therapy: No prior bone marrow or peripheral blood stem
cell transplantation, unless undergoing second transplant of a tandem transplant regimen,
with no complications after first transplant No concurrent interleukin-11 Chemotherapy: No
other concurrent cytotoxic chemotherapy, except intrathecal methotrexate for CNS
involvement Endocrine therapy: Not specified Radiotherapy: No prior extensive radiotherapy
that would preclude total body irradiation Surgery: Not specified Other: At least 30 days
since prior investigational devices or drugs, except Baxter Isolex i column No other
concurrent investigational agents No concurrent prophylactic oral cryotherapy during