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.

Condition	Treatment or Intervention	Phase
Leukemia Lymphoma Multiple Myeloma	Drug: cyclophosphamide  Drug: etoposide  Drug: filgrastim  Drug: ifosfamide  Drug: recombinant human keratinocyte growth factor	Phase II

Further Study Details: 

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.

PROTOCOL 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.

Ages Eligible for Study:  12 Years   -   65 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--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

--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 chemotherapy

--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 after study

California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States

Study chairs or principal investigators

Christos E. Emmanouilides,  Study Chair,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000067362; UCLA-9812041; NCI-G99-1609; AMGEN-KGF-980231-03
Record last reviewed:  May 2004
Last Updated:  October 13, 2004
Record first received:  December 10, 1999
ClinicalTrials.gov Identifier:  NCT00004132
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08