Fludarabine and Cyclophosphamide Followed by Peripheral Stem Cell Transplant in Treating Patients With Leukemia or Lymphoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology ( Cancer and Leukemia Group B )
ClinicalTrials.gov Identifier:
NCT00006252
First received: September 11, 2000
Last updated: September 25, 2013
Last verified: April 2011
  Purpose

RATIONALE: Giving chemotherapy drugs, such as fludarabine and cyclophosphamide, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

PURPOSE: This phase II trial is studying how well fludarabine and cyclophosphamide followed by peripheral stem cell transplant works in treating patients with leukemia or lymphoma.


Condition Intervention Phase
Leukemia
Lymphoma
Drug: fludarabine phosphate
Drug: Cyclophosphamide
Biological: PBSC
Drug: G-CSF
Biological: Donor lymphocytes
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Minimal Ablation and Cellular Immune Therapy of Chronic Lymphocytic Leukemia, Prolymphocytic Leukemia, Low-Grade Non-Hodgkin's Lymphoma, and Mantle Cell Lymphoma With Allogeneic Donor Stem Cells

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Treatment-related mortality within the first 6 months post-transplant [ Time Frame: 6 months post chemo initiation ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Response [ Time Frame: 6 months & 12 months ] [ Designated as safety issue: No ]
  • Percentage of patients achieving complete donor chimerism or mixed donor chimerism [ Time Frame: 90 days post transplant ] [ Designated as safety issue: No ]
  • Survival [ Time Frame: 5 years post study entry ] [ Designated as safety issue: No ]
    Disease free and overall survival will be assessed


Enrollment: 47
Study Start Date: February 2001
Study Completion Date: October 2011
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Allogeneic Stem Cell Tx
minimal ablation and cellular immune therapy with allogeneic donor stem cell therapy
Drug: fludarabine phosphate
30 mg/sq m/day IV infusion for 5 days (Days -7 thru -3)
Drug: Cyclophosphamide
1 g/sq m/day IV infusion x 3 days (Days -5 thru -3)
Biological: PBSC
2-8,000,000/kg CD34+ cells via infusion on Day 0
Drug: G-CSF
5 ug/kg/day subQ injection until ANC > 1000/uL for 3 days beginning Day 5
Biological: Donor lymphocytes
10,000,000 CD3+ cells/kg via infusion

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00006252

Locations
United States, California
Rebecca and John Moores UCSD Cancer Center
La Jolla, California, United States, 92093-0658
Veterans Affairs Medical Center - San Diego
San Diego, California, United States, 92161
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Delaware
Beebe Medical Center
Lewes, Delaware, United States, 19958
CCOP - Christiana Care Health Services
Newark, Delaware, United States, 19713
St. Francis Hospital
Wilmington, Delaware, United States, 19805
United States, Iowa
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, United States, 52242
United States, Maryland
Union Hospital Cancer Center at Union Hospital
Elkton MD, Maryland, United States, 21921
United States, Massachusetts
UMASS Memorial Cancer Center - University Campus
Worcester, Massachusetts, United States, 01655
United States, New Jersey
Cancer Institute of New Jersey at the Cooper University Hospital - Voorhees
Voorhees, New Jersey, United States, 08043
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Elmhurst Hospital Center
Elmhurst, New York, United States, 11373
Queens Cancer Center of Queens Hospital
Jamaica, New York, United States, 11432
Mount Sinai Medical Center
New York, New York, United States, 10029
United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
Columbus, Ohio, United States, 43210-1240
United States, Pennsylvania
Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, United States, 15224-1791
United States, Virginia
Massey Cancer Center at Virginia Commonwealth University
Richmond, Virginia, United States, 23298-0037
Sponsors and Collaborators
Cancer and Leukemia Group B
Investigators
Study Chair: Thomas C. Shea, MD UNC Lineberger Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Shea TC, Johnston J, Walsh W, et al.: Reduced intensity allogeneic transplantation provides high disease-free and overall survival in patients (pts) with advanced indolent NHL and CLL: CALGB 109901. [Abstract] Blood 110 (11): A-486, 2007.

Responsible Party: Alliance for Clinical Trials in Oncology ( Cancer and Leukemia Group B )
ClinicalTrials.gov Identifier: NCT00006252     History of Changes
Other Study ID Numbers: CDR0000068185, U10CA031946, CALGB-109901
Study First Received: September 11, 2000
Last Updated: September 25, 2013
Health Authority: United States: Federal Government

Keywords provided by Alliance for Clinical Trials in Oncology:
refractory chronic lymphocytic leukemia
stage I grade 1 follicular lymphoma
stage I grade 2 follicular lymphoma
stage I adult diffuse small cleaved cell lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV adult diffuse small cleaved cell lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
prolymphocytic leukemia
stage I mantle cell lymphoma
contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II adult diffuse small cleaved cell lymphoma
contiguous stage II mantle cell lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
recurrent mantle cell lymphoma
contiguous stage II small lymphocytic lymphoma
contiguous stage II marginal zone lymphoma
noncontiguous stage II small lymphocytic lymphoma
noncontiguous stage II marginal zone lymphoma

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Prolymphocytic
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Fludarabine monophosphate
Fludarabine
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic

ClinicalTrials.gov processed this record on April 23, 2014