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.

Condition	Treatment or Intervention	Phase
Leukemia Lymphoma	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 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.

PROTOCOL 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 15 months.

Ages Eligible for Study:  18 Years   -   65 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--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

--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

--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 contraception

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States

Study chairs or principal investigators

Eric W. Hedrick,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000067261; MSKCC-99029; NCI-G99-1574; AMGEN-KGF-980231-04
Record last reviewed:  May 2004
Last Updated:  October 13, 2004
Record first received:  December 10, 1999
ClinicalTrials.gov Identifier:  NCT00004061
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08