RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of cyclophosphamide and filgrastim in treating patients with stage IV, relapsed, or refractory low-grade follicular non-Hodgkin's lymphoma.

Condition	Treatment or Intervention	Phase
stage IV grade II follicular mixed cell lymphoma recurrent grade I follicular small cleaved cell lymphoma recurrent grade II follicular mixed cell lymphoma stage IV grade I follicular small cleaved cell lymphoma	Drug: cyclophosphamide  Drug: filgrastim	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the feasibility of high-dose cyclophosphamide and filgrastim (G-CSF) in patients with stage IV, relapsed, or progressive low-grade follicular non-Hodgkin's lymphoma. II. Determine the toxic effects of this regimen in these patients, including those with marrow involvement. III. Determine the rates of complete remission (CR) and partial remission and time to failure in previously treated and untreated patients. IV. Determine the effectiveness of this regimen in eradicating bcl-2 rearrangements, as determined by polymerase chain reaction (PCR), in previously untreated patients. V. Correlate the duration of CR to PCR results in responding patients.

PROTOCOL OUTLINE: Patients are stratified according to prior treatment (yes vs no). Patients receive cyclophosphamide IV over 90 minutes on day 1 and filgrastim (G-CSF) subcutaneously beginning on day 3 and continuing until blood counts recover. Treatment continues every 2 weeks for 4 courses in the absence of disease progression or stable disease. Patients who achieve complete remission (CR) after completion of course 4 receive 2 additional courses. Patients who achieve partial remission (PR) after completion of course 4 receive 2 additional courses, and those who achieve CR after completion of course 6 receive 2 additional courses. Patients are followed every 2 months for 6 months, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 60 patients (30 per stratum) will be accrued for this study.

Ages Eligible for Study:  18 Years   -   55 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven low-grade non-Hodgkin's lymphoma of the following subtypes: Follicular, predominantly small cleaved cell; Follicular mixed (small cleaved and large cell)
• Previously treated on Protocol CLB 8691 or previously untreated
• Previously untreated patients with Stage IV disease (Ann Arbor classification) must meet the following conditions: Documented bone marrow involvement; Lymph node biopsy must not show higher grade lymphoma; At least 1 additional risk factor as follows: At least 2 extranodal sites; Nodes or nodal group at least 5 cm; Male
• Previously treated patients must have progressed or relapsed on Protocol CLB-8691; Recurrence should be documented by biopsy if possible
• Bidimensionally measurable disease by physical exam, radiograph, CT, or MRI (sonography and barium studies alone not acceptable) Measurable liver disease defined as: Mass greater than 3.5 cm on CT, MRI, or ultrasound OR Histologically documented lymphomatous hepatomegaly more than 5 cm below the costal margin; The following disease manifestations are not considered measurable: Ascites or pleural effusion; Bony disease (lytic lesions on x-ray should be documented and followed); CNS lesions; Bone marrow involvement
• No lymphomatous involvement (including CNS lymphoma) requiring immediate radiotherapy

[A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.]

--Prior/Concurrent Therapy--

• Biologic therapy: Prior interferon only on Protocol CLB-8691 allowed
• Chemotherapy: Prior oral cyclophosphamide only on Protocol CLB-8691 allowed; No concurrent chemotherapy
• Endocrine therapy: No chronic steroids for other health problems; No concurrent steroids for any condition including documented CNS metastases, adrenal failure, or septic shock; Nonsteroidal hormonal drugs for nondisease related problems allowed (e.g., insulin for diabetes)
• Radiotherapy: See Disease Characteristics; No prior radiotherapy; No concurrent palliative radiotherapy
• Surgery: At least 2 weeks since prior major surgery
• Other: No other prior therapy

--Patient Characteristics--

• Age: 18 to physiologic 55; Patients over 55 are eligible only if study chairperson agrees that the patient can tolerate intensive chemotherapy
• Performance status: Zubrod 0-1
• Life expectancy: More than 2 years
• Hematopoietic: Granulocyte count at least 1,500/mm3; Platelet count at least 100,000/mm3; Hemoglobin at least 9.0 g/dL
• Hepatic: Bilirubin less than 1.5 times normal
• Renal: Creatinine less than 1.5 times normal
• Cardiovascular: LVEF at least 50% No acute changes or arrhythmias on ECG; No cardiomegaly on chest x-ray or physical exam; No uncontrolled or severe cardiovascular disease, including myocardial infarction within the past 6 months or congestive heart failure (CHF); No active cardiac problems, including compensated CHF or angina
• Other: HIV negative; No other malignancy within the past 5 years except curatively treated basal cell skin cancer or carcinoma in situ of the cervix; No active uncontrolled bacterial, viral, or fungal infection No other serious medical illness that would limit survival to less than 2 years; No psychiatric condition that would preclude informed consent or compliance; No uncontrolled duodenal ulcer; Not pregnant; Fertile patients must use effective contraception

Illinois
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637,  United States
Iowa
      University of Iowa Hospitals and Clinics, Iowa City,  Iowa,  52242,  United States
Maryland
      Marlene & Stewart Greenebaum Cancer Center, University of Maryland, Baltimore,  Maryland,  21201,  United States
Massachusetts
      University of Massachusetts Memorial Medical Center, Worcester,  Massachusetts,  01655,  United States
Missouri
      Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States
      Ellis Fischel Cancer Center - Columbia, Columbia,  Missouri,  65203,  United States
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States
New Hampshire
      Norris Cotton Cancer Center, Lebanon,  New Hampshire,  03756,  United States
New York
      CCOP - North Shore University Hospital, Manhasset,  New York,  11030,  United States
      Mount Sinai Medical Center, NY, New York,  New York,  10029,  United States
      State University of New York - Upstate Medical University, Syracuse,  New York,  13210,  United States
North Carolina
      CCOP - Southeast Cancer Control Consortium, Winston Salem,  North Carolina,  27104-4241,  United States
      Comprehensive Cancer Center of Wake Forest University Baptist Medical Center, Winston Salem,  North Carolina,  27157-1082,  United States
Rhode Island
      Rhode Island Hospital, Providence,  Rhode Island,  02903,  United States
Tennessee
      University of Tennessee, Memphis Cancer Center, Memphis,  Tennessee,  38103,  United States

Study chairs or principal investigators

Robert T. Perri,  Study Chair,  Cancer and Leukemia Group B   

Study ID Numbers:  CDR0000077861; CLB-9150
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002501
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08