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

Primary Purpose

Leukemia, Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
fludarabine phosphate
Cyclophosphamide
PBSC
G-CSF
Donor lymphocytes
Sponsored by
Cancer and Leukemia Group B
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring 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, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, stage I marginal zone lymphoma, stage I small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage III marginal zone lymphoma, stage IV small lymphocytic lymphoma, stage IV marginal zone lymphoma

Eligibility Criteria

undefined - 69 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Rebecca and John Moores UCSD Cancer Center
  • Veterans Affairs Medical Center - San Diego
  • UCSF Comprehensive Cancer Center
  • Beebe Medical Center
  • CCOP - Christiana Care Health Services
  • St. Francis Hospital
  • Holden Comprehensive Cancer Center at University of Iowa
  • Union Hospital Cancer Center at Union Hospital
  • UMASS Memorial Cancer Center - University Campus
  • Cancer Institute of New Jersey at the Cooper University Hospital - Voorhees
  • Roswell Park Cancer Institute
  • Elmhurst Hospital Center
  • Queens Cancer Center of Queens Hospital
  • Mount Sinai Medical Center
  • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
  • Wake Forest University Comprehensive Cancer Center
  • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
  • Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
  • Massey Cancer Center at Virginia Commonwealth University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Allogeneic Stem Cell Tx

Arm Description

minimal ablation and cellular immune therapy with allogeneic donor stem cell therapy

Outcomes

Primary Outcome Measures

Treatment-related mortality within the first 6 months post-transplant

Secondary Outcome Measures

Response
Percentage of patients achieving complete donor chimerism or mixed donor chimerism
Survival
Disease free and overall survival will be assessed

Full Information

First Posted
September 11, 2000
Last Updated
July 15, 2016
Sponsor
Cancer and Leukemia Group B
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00006252
Brief Title
Fludarabine and Cyclophosphamide Followed by Peripheral Stem Cell Transplant in Treating Patients With Leukemia or Lymphoma
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2016
Overall Recruitment Status
Completed
Study Start Date
February 2001 (undefined)
Primary Completion Date
January 2007 (Actual)
Study Completion Date
October 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cancer and Leukemia Group B
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma
Keywords
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, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, stage I marginal zone lymphoma, stage I small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage III marginal zone lymphoma, stage IV small lymphocytic lymphoma, stage IV marginal zone lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
47 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Allogeneic Stem Cell Tx
Arm Type
Experimental
Arm Description
minimal ablation and cellular immune therapy with allogeneic donor stem cell therapy
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Intervention Description
30 mg/sq m/day IV infusion for 5 days (Days -7 thru -3)
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
1 g/sq m/day IV infusion x 3 days (Days -5 thru -3)
Intervention Type
Biological
Intervention Name(s)
PBSC
Intervention Description
2-8,000,000/kg CD34+ cells via infusion on Day 0
Intervention Type
Drug
Intervention Name(s)
G-CSF
Intervention Description
5 ug/kg/day subQ injection until ANC > 1000/uL for 3 days beginning Day 5
Intervention Type
Biological
Intervention Name(s)
Donor lymphocytes
Intervention Description
10,000,000 CD3+ cells/kg via infusion
Primary Outcome Measure Information:
Title
Treatment-related mortality within the first 6 months post-transplant
Time Frame
6 months post chemo initiation
Secondary Outcome Measure Information:
Title
Response
Time Frame
6 months & 12 months
Title
Percentage of patients achieving complete donor chimerism or mixed donor chimerism
Time Frame
90 days post transplant
Title
Survival
Description
Disease free and overall survival will be assessed
Time Frame
5 years post study entry

10. Eligibility

Sex
All
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Shea, MD
Organizational Affiliation
UNC Lineberger Comprehensive Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Rebecca and John Moores UCSD Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093-0658
Country
United States
Facility Name
Veterans Affairs Medical Center - San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92161
Country
United States
Facility Name
UCSF Comprehensive Cancer Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Beebe Medical Center
City
Lewes
State/Province
Delaware
ZIP/Postal Code
19958
Country
United States
Facility Name
CCOP - Christiana Care Health Services
City
Newark
State/Province
Delaware
ZIP/Postal Code
19713
Country
United States
Facility Name
St. Francis Hospital
City
Wilmington
State/Province
Delaware
ZIP/Postal Code
19805
Country
United States
Facility Name
Holden Comprehensive Cancer Center at University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Union Hospital Cancer Center at Union Hospital
City
Elkton MD
State/Province
Maryland
ZIP/Postal Code
21921
Country
United States
Facility Name
UMASS Memorial Cancer Center - University Campus
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
Cancer Institute of New Jersey at the Cooper University Hospital - Voorhees
City
Voorhees
State/Province
New Jersey
ZIP/Postal Code
08043
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263-0001
Country
United States
Facility Name
Elmhurst Hospital Center
City
Elmhurst
State/Province
New York
ZIP/Postal Code
11373
Country
United States
Facility Name
Queens Cancer Center of Queens Hospital
City
Jamaica
State/Province
New York
ZIP/Postal Code
11432
Country
United States
Facility Name
Mount Sinai Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599-7295
Country
United States
Facility Name
Wake Forest University Comprehensive Cancer Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157-1096
Country
United States
Facility Name
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210-1240
Country
United States
Facility Name
Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224-1791
Country
United States
Facility Name
Massey Cancer Center at Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298-0037
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21296675
Citation
Shea T, Johnson J, Westervelt P, Farag S, McCarty J, Bashey A, Isola L, Baxter-Lowe LA, Kelly M, Owzar K, Linker C; Cancer and Leukemia Group B. Reduced-intensity allogeneic transplantation provides high event-free and overall survival in patients with advanced indolent B cell malignancies: CALGB 109901. Biol Blood Marrow Transplant. 2011 Sep;17(9):1395-403. doi: 10.1016/j.bbmt.2011.01.016. Epub 2011 Feb 3.
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Fludarabine and Cyclophosphamide Followed by Peripheral Stem Cell Transplant in Treating Patients With Leukemia or Lymphoma

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