RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with autologous peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus peripheral stem cell transplantation in treating patients who have relapsed non-Hodgkin's lymphoma.

Condition	Treatment or Intervention	Phase
recurrent grade III follicular large cell lymphoma recurrent adult immunoblastic large cell lymphoma recurrent adult diffuse mixed cell lymphoma recurrent adult diffuse large cell lymphoma	Drug: cyclophosphamide  Drug: cytarabine  Drug: etoposide  Drug: filgrastim  Drug: melphalan  Drug: mitoxantrone  Drug: paclitaxel  Drug: stem cell factor	Phase II

Further Study Details: 

OBJECTIVES: I. Determine how many patients with chemotherapy sensitive relapsed non-Hodgkin's lymphoma receiving sequential high dose chemotherapy achieve a collection of a minimum 5 million CD34+ cells/kg in one large volume apheresis.

II. Determine the feasibility and safety of this regimen in these patients.

III. Determine disease free and overall survival of patients receiving this regimen.

PROTOCOL OUTLINE: Patients receive cyclophosphamide IV over 1 hour followed by paclitaxel IV over 24 hours on day 1. Filgrastim (G-CSF) and stem cell factor (SCF) are administered subcutaneously beginning on day 3 for approximately 7-14 days (until the completion of leukapheresis). Peripheral blood stem cells (PBSC) are collected over 3-5 days.

Three weeks after leukapheresis is completed, patients receive cytarabine IV over 2 hours twice a day on days -6 to -3. Mitoxantrone IV is administered over 1 hour on day -6. CD34+ PBSC are reinfused on day 0.

Four weeks later, patients receive etoposide IV over 11 hours on day -2 and melphalan IV over 30 minutes twice on day -1. CD34+ PBSC are reinfused on day 0.

Concurrent G-CSF is administered subcutaneously and continues until blood counts recover.

Patients are followed at 4 weeks, every 3 months for the first 2 years, and then every 6 months for the next 2 years.

PROJECTED ACCRUAL: A total of 12 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed follicular or diffuse large cell, diffuse mixed, or immunoblastic non-Hodgkin's lymphoma (working formulation D, F, G, or H)
• First relapse from a complete response or complete response unconfirmed after a front line chemotherapy regimen (e.g., CHOP-like regimen)
• Second relapse from partial response after 2-4 courses of second line standard dose chemotherapy (e.g., MINE, EPOCH, or platinum-containing regimens)
• No more than 1 salvage treatment regimen
• No CNS involvement

--Prior/Concurrent Therapy--

• Biologic therapy: At least 1 week since prior hematopoietic growth factors
• Chemotherapy: See Disease Characteristics; At least 4 weeks since prior chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: No prior radiotherapy to relapsed sites of vital organs (except as part of initial treatment); At least 4 weeks since prior palliative radiotherapy to bulky nodes
• Surgery: At least 2 weeks since prior major surgery
• Other: No other concurrent investigational drugs; No concurrent beta adrenergic blocking agents

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-1
• Life expectancy: Not specified
• Hematopoietic: Absolute neutrophil count at least 1,500/mm3; Platelet count at least 100,000/mm3
• Hepatic: Transaminases no greater than 2 times upper limit of normal; Bilirubin no greater than 2 mg/dL (unless due to biopsy proven lymphoma); No chronic viral hepatitis
• Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 60 mL/min; No overt renal insufficiency
• Cardiovascular: LVEF at least 45%; No congestive heart failure (New York Heart Association class III or IV); No myocardial infarction within past 6 months; No uncontrolled hypertension (diastolic blood pressure greater than 115 mmHg); No unstable angina; No coronary angioplasty within past 6 months; No uncontrolled atrial or ventricular cardiac arrhythmias
• Pulmonary: DLCO and FEV1 at least 45% of predicted; No severe pulmonary disease; No seasonal or recurrent asthma within past 10 years; No asthmatic symptoms (e.g., wheezing) related to current respiratory tract infection; No concurrent symptoms of bronchoconstriction; No anaphylactic/anaphylactoid-type event manifested by disseminated urticaria, laryngeal edema, and/or bronchospasm
• Other: Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception; HIV negative; No prior malignancy within the past 5 years except carcinoma in situ of the cervix or basal cell or squamous cell skin cancer; No severe medical or psychiatric illness (including severe depression); No active peptic ulcer disease; No poorly controlled diabetes; No allergy to insect vemons; No active history of angioedema or recurrent urticaria (an isolated episode of urticaria is allowed); No active infection; No fever greater than 38.2 degrees C (except fevers due to B symptoms); No allergy to E. coli derived products

Pennsylvania
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111,  United States

Study chairs or principal investigators

Russell J. Schilder,  Study Chair,  Fox Chase Cancer Center   

Study ID Numbers:  CDR0000067156; FCCC-98052; NCI-G99-1541
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003957
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08