RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy.

PURPOSE: Phase II trial to study the effectiveness of fludarabine and cyclophosphamide followed by peripheral stem cell transplantation in treating patients who have leukemia or lymphoma.

Condition	Treatment or Intervention	Phase
adult non-Hodgkin's lymphoma Chronic Lymphocytic Leukemia Prolymphocytic Leukemia	Drug: allogeneic lymphocytes  Drug: cyclophosphamide  Drug: filgrastim  Drug: fludarabine  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: leukocyte therapy  Procedure: peripheral blood lymphocyte therapy  Procedure: peripheral blood stem cell transplantation	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the feasibility of fludarabine and cyclophosphamide followed by allogeneic peripheral blood stem cell transplantation, in terms of 6-month treatment-related mortality, in patients with chronic lymphocytic leukemia, prolymphocytic leukemia, low-grade non-Hodgkin's lymphoma, or mantle cell lymphoma.
• Determine the 6-month and 12-month probabilities of response in patients treated with this regimen.
• Determine the time to disease progression in patients responding to this regimen.
• Determine the percentage of donor chimerism achieved in patients treated with this regimen.
• Determine the risk of acute and chronic graft-versus-host disease in patients treated with this regimen.
• Determine the toxic effects of this regimen in these patients.
• Determine the overall survival and disease-free survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive fludarabine IV over 30 minutes on days -7 to -3 and cyclophosphamide IV over 1 to 2 hours on days -5 to -3. Patients undergo allogeneic peripheral blood stem cell transplantation on days 0-1. Patients then receive filgrastim (G-CSF) subcutaneously daily beginning on day 5 and continuing until blood counts recover.

Patients with no signs of active graft-versus host disease and stable or progressive disease receive donor lymphocytes IV over 2 hours beginning after day 120. Patients may receive a total of 3 infusions at least 8 weeks apart if disease remains stable or progressive.

Patients are followed every 3 months for 2 years and then every 6 months for 5 years.

PROJECTED ACCRUAL: A maximum of 45 patients will be accrued for this study.

Ages Eligible for Study:  up to  69 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• One of the following histologically confirmed diagnoses:
• Chronic lymphocytic leukemia
• Absolute lymphocytosis greater than 5,000/mm^3
• Morphologically mature lymphocytes with less than 55% prolymphocytes
• Lymphocyte phenotypic expression of CD19 and CD5
• Failed at least 1 prior regimen
• Progressive lymphocytosis with more than 50% increase in peripheral lymphocytosis or a progressive lymph node or spleen enlargement (at least 25% enlargement or the appearance of new lymph nodes) that persists for at least 4 weeks despite concurrent or prior drug treatment OR
• At least 1 of the following high-risk factors and not in first complete remission
• 17p deletion
• 11q deletion
• Unmutated VH gene status
• p53 mutations
• Prolymphocytic leukemia (PLL)
• Absolute lymphocytosis greater than 5,000/mm^3
• Morphologically mature lymphocytes with more than 55% prolymphocytes
• Low-grade non-Hodgkin's lymphoma
• Small lymphocytic lymphoma
• Follicular center lymphoma (grade I or II)
• Diffuse (predominately small cell type)
• Marginal zone, B-cell lymphoma
• No transformed lymphoma
• Failure of at least 1 prior regimen OR
• At least 3 of the following risk factors:
• Over 60 years of age
• Performance status greater than 1
• LDH greater than normal
• More than 1 site of extranodal disease
• Disease stage III or IV
• Mantle cell lymphoma
• Any stage
• Ineligible for protocol CALGB-59908
• At least 1 prior treatment regimen
• At least 1 of the following:
• Immunophenotypic expression of CD5 and CD19 and absence of CD23
• Cytogenetic analysis with presence of t(11;14)
• Overexpression of cyclin D1
• Rearrangement of BCL1 gene
• Responsive or stable disease to most recent prior therapy
• Prior therapy for PLL not required
• Must have HLA identical sibling (6/6) donor by serologic typing (A, B, DR)
• No syngeneic donors
• No age restriction NOTE: 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.

PATIENT CHARACTERISTICS: Age:

• Under 70

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Granulocyte count at least 500/mm^3*
• Platelet count at least 50,000/mm^3* NOTE: *Unless attributable to disease

Hepatic:

• Bilirubin no greater than 3 times upper limit of normal (ULN)*
• AST no greater than 3 times ULN* NOTE: *Unless attributable to disease

Renal:

• Creatinine clearance at least 40 mL/min, unless attributable to disease

Cardiovascular:

• LVEF at least 30% by MUGA

Pulmonary:

• DLCO greater than 40%
• No symptomatic pulmonary disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No uncontrolled diabetes mellitus
• No active serious infection
• No known hypersensitivity to E. coli-derived products

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No prior autologous transplantation

Chemotherapy:

• At least 4 weeks since prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy

Surgery:

• At least 4 weeks since prior surgery

Alabama
      Northeast Alabama Regional Medical Center, Anniston,  Alabama,  36207,  United States; Recruiting
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35294-3300,  United States; Recruiting
California
      Naval Medical Center - San Diego, San Diego,  California,  92134-3202,  United States; Recruiting
      Rebecca and John Moores UCSD Cancer Center, La Jolla,  California,  92093-0690,  United States; Recruiting
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94115,  United States; Recruiting
      Veterans Affairs Medical Center - San Diego, San Diego,  California,  92161,  United States; Recruiting
Delaware
      CCOP - Christiana Care Health Services, Newark,  Delaware,  19713,  United States; Recruiting
District of Columbia
      Veterans Affairs Medical Center - Washington, DC, Washington,  District of Columbia,  20422,  United States; Recruiting
Florida
      Broward General Medical Center, Fort Lauderdale,  Florida,  33316,  United States; Recruiting
      Memorial Cancer Institute at Memorial Regional Hospital, Hollywood,  Florida,  33021,  United States; Recruiting
Illinois
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61615-7828,  United States; Recruiting
      Louis A. Weiss Memorial Hospital, Chicago,  Illinois,  60640,  United States; Recruiting
      Lutheran General Cancer Care Center, Park Ridge,  Illinois,  60068-1270,  United States; Recruiting
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States; Recruiting
      West Suburban Center for Cancer Care, River Forest,  Illinois,  60305,  United States; Recruiting
Indiana
      Fort Wayne Medical Oncology and Hematology, Incorporated, Fort Wayne,  Indiana,  46885-5099,  United States; Recruiting
Iowa
      Holden Comprehensive Cancer Center at University of Iowa, Iowa City,  Iowa,  52242-1009,  United States; Recruiting
Kentucky
      Baptist Hospital East - Louisville, Louisville,  Kentucky,  40207,  United States; Recruiting
Maine
      Maine Center for Cancer Medicine and Blood Disorders - Scarborough, Scarborough,  Maine,  04074,  United States; Recruiting
Maryland
      Greenebaum Cancer Center at University of Maryland Medical Center, Baltimore,  Maryland,  21201,  United States; Recruiting
Massachusetts
      Brigham and Women's Hospital, Boston,  Massachusetts,  02115,  United States; Recruiting
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
      Lahey Clinic Medical Center - Burlington, Burlington,  Massachusetts,  01805,  United States; Recruiting
      Massachusetts General Hospital Cancer Center, Boston,  Massachusetts,  02114-2698,  United States; Recruiting
      UMASS Memorial Cancer Center - University Campus, Worcester,  Massachusetts,  01655,  United States; Recruiting
Michigan
      Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph, Saint Joseph,  Michigan,  49085,  United States; Recruiting
Minnesota
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States; Recruiting
Missouri
      Boone Hospital Center, Columbia,  Missouri,  65201,  United States; Recruiting
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States; Recruiting
      Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States; Recruiting
Nebraska
      UNMC Eppley Cancer Center at the University of Nebraska Medical Center, Omaha,  Nebraska,  68198-7680,  United States; Recruiting
Nevada
      Veterans Affairs Medical Center - Las Vegas, Las Vegas,  Nevada,  89106,  United States; Recruiting
New Hampshire
      New Hampshire Oncology-Hematology, PA - Hooksett, Hooksett,  New Hampshire,  03106,  United States; Recruiting
      Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon,  New Hampshire,  03756-0002,  United States; Recruiting
New Jersey
      Cancer Institute of New Jersey at the Cooper University Hospital, Camden,  New Jersey,  08103,  United States; Recruiting
      St. Joseph's Hospital and Medical Center, Paterson,  New Jersey,  07503,  United States; Recruiting
New York
      Elmhurst Hospital Center, Elmhurst,  New York,  11373,  United States; Recruiting
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting
      Mount Sinai Medical Center, New York,  New York,  10029,  United States; Recruiting
      New York Weill Cornell Cancer Center at Cornell University, New York,  New York,  10021,  United States; Recruiting
      North Shore University Hospital, Manhasset,  New York,  11030,  United States; Recruiting
      Queens Cancer Center of Queens Hospital, Jamaica,  New York,  11432,  United States; Recruiting
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States; Recruiting
      SUNY Upstate Medical University Hospital, Syracuse,  New York,  13210,  United States; Recruiting
North Carolina
      Blumenthal Cancer Center at Carolinas Medical Center, Charlotte,  North Carolina,  28232-2861,  United States; Recruiting
      Cape Fear Valley Medical Center, Fayetteville,  North Carolina,  28302-2000,  United States; Recruiting
      Comprehensive Cancer Center at Moore Regional Hospital, Pinehurst,  North Carolina,  28374,  United States; Recruiting
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States; Recruiting
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States; Recruiting
      Lenoir Memorial Cancer Center, Kinston,  North Carolina,  28503-1678,  United States; Recruiting
      NorthEast Oncology Associates - Concord, Concord,  North Carolina,  28025,  United States; Recruiting
      Veterans Affairs Medical Center - Asheville, Asheville,  North Carolina,  28805-9913,  United States; Recruiting
      Zimmer Cancer Center at New Hanover Regional Medical Center, Wilmington,  North Carolina,  28402-9025,  United States; Recruiting
Ohio
      Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University, Columbus,  Ohio,  43210-1240,  United States; Recruiting
Oklahoma
      Oklahoma University Medical Center, Oklahoma City,  Oklahoma,  73104,  United States; Recruiting
South Carolina
      Cancer Centers of the Carolinas - Eastside, Greenville,  South Carolina,  29615,  United States; Recruiting
      Palmetto Richland Memorial Hospital, Columbia,  South Carolina,  29203,  United States; Recruiting
Texas
      Veterans Affairs Medical Center - Dallas, Dallas,  Texas,  75219,  United States; Recruiting
Vermont
      Vermont Cancer Center at University of Vermont, Burlington,  Vermont,  05401-3498,  United States; Recruiting
Virginia
      Martha Jefferson Hospital, Charlottesville,  Virginia,  22902,  United States; Recruiting
      Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke, Roanoke,  Virginia,  24014,  United States; Recruiting
      Virginia Oncology Associates - Norfolk, Norfolk,  Virginia,  23502,  United States; Recruiting
West Virginia
      St. Mary's Medical Center, Huntington,  West Virginia,  25701,  United States; Recruiting
Wisconsin
      Vince Lombardi Cancer Clinic at St. Luke's Medical Center, Milwaukee,  Wisconsin,  53215,  United States; Recruiting

Study chairs or principal investigators

Thomas C. Shea, MD,  Study Chair,  UNC Lineberger Comprehensive Cancer Center   

Study ID Numbers:  CDR0000068185; CALGB-109901; NCT00006252
Record last reviewed:  July 2004
Last Updated:  April 4, 2005
Record first received:  September 11, 2000
ClinicalTrials.gov Identifier:  NCT00006252
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08