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S0501 Fludarabine, Melphalan, and Donor Stem Cell Transplant Followed By Tacrolimus and Methotrexate in Treating Patients for Relapsed Lymphoma

Primary Purpose

Lymphoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
fludarabine phosphate
melphalan
methotrexate
tacrolimus
allogeneic bone marrow transplantation
peripheral blood stem cell transplantation
Sponsored by
SWOG Cancer Research Network
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring recurrent adult Hodgkin lymphoma, recurrent small lymphocytic lymphoma, recurrent mantle cell lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse large cell lymphoma

Eligibility Criteria

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

DISEASE CHARACTERISTICS: Diagnosis of lymphoma of 1 of the following types: Diffuse large B-cell lymphoma Follicular lymphoma Grades 1, 2, or 3 Primary mediastinal lymphoma Mantle cell lymphoma Small lymphocytic lymphoma Hodgkin's lymphoma Transformed lymphoma Relapsed after prior autologous bone marrow transplantation (BMT) More than 180 days post BMT Received ≥ 1 course of chemotherapy after BMT relapse Achieved a complete response OR a partial response to chemotherapy Largest residual tumor dimension ≤ 2 cm No clinical or laboratory evidence of CNS involvement by lymphoma HLA-identical donor available, meeting 1 of the following criteria: Sibling donor with 5/6 or 6/6 alleles matching by genotyping No monozygotic identical twins Unrelated donor with 10/10 alleles matching by genotyping PATIENT CHARACTERISTICS: Age 18 and over Performance status Zubrod 0-2 Life expectancy Not specified Hematopoietic Not specified Hepatic Not specified Renal Not specified Cardiovascular LVEF ≥ 40% by MUGA or 2-D echocardiogram (2-D ECHO) No significant cardiac abnormalities by MUGA or 2-D ECHO No uncompensated coronary artery disease by ECG or physical exam None of the following within the past 6 months: Myocardial infarction Unstable angina Uncontrolled atrial fibrillation None of the following within the past 3 months: Severe peripheral vascular disease Venous stasis ulcers Deep venous or arterial thrombosis No uncontrolled hypertension Pulmonary DLCO (corrected) and total lung capacity ≥ 40% of predicted No requirement for continuous supplemental oxygen Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception HIV negative No AIDS No active bacterial, viral, or fungal infection No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix No history of uncontrolled seizures No diabetic ulcers within the past 3 months PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics No more than 1 prior bone marrow transplantation Chemotherapy See Disease Characteristics More than 21 days since prior chemotherapy and recovered Endocrine therapy Not specified Radiotherapy More than 4 weeks since prior radiotherapy Surgery More than 4 weeks since prior major surgery except placement of a venous access device

Sites / Locations

  • Cardinal Bernardin Cancer Center at Loyola University Medical Center
  • St. Francis Hospital and Health Centers - Beech Grove Campus
  • Reid Hospital & Health Care Services, Incorporated
  • Cancer Center of Kansas, PA - Chanute
  • Cancer Center of Kansas, PA - Dodge City
  • Cancer Center of Kansas, PA - El Dorado
  • Cancer Center of Kansas, PA - Kingman
  • Southwest Medical Center
  • Cancer Center of Kansas, PA - Newton
  • Cancer Center of Kansas, PA - Parsons
  • Cancer Center of Kansas, PA - Pratt
  • Cancer Center of Kansas, PA - Salina
  • Cancer Center of Kansas, PA - Wellington
  • Associates in Womens Health, PA - North Review
  • Cancer Center of Kansas, PA - Medical Arts Tower
  • Cancer Center of Kansas, PA - Wichita
  • CCOP - Wichita
  • Via Christi Cancer Center at Via Christi Regional Medical Center
  • Cancer Center of Kansas, PA - Winfield
  • Highland Hospital of Rochester
  • Interlakes Oncology/Hematology PC
  • James P. Wilmot Cancer Center at University of Rochester Medical Center
  • Grandview Hospital
  • Good Samaritan Hospital
  • David L. Rike Cancer Center at Miami Valley Hospital
  • Veterans Affairs Medical Center - Dayton
  • CCOP - Dayton
  • Blanchard Valley Medical Associates
  • Charles F. Kettering Memorial Hospital
  • Middletown Regional Hospital
  • UVMC Cancer Care Center at Upper Valley Medical Center
  • United States Air Force Medical Center - Wright-Patterson
  • Ruth G. McMillan Cancer Center at Greene Memorial Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Nonmyeloablative allogeneic stem cell transplant

Arm Description

Patients are given fludarabine 30 mg/m^2 on days -6 to -2 and melphalan 70 mg/m^2 on days -3 and -2, then transplanted with donor peripheral blood stem cells or harvested bone marrow stem cells on day 0. Patients are then given post-transplant immunosuppression consisting of tacrolimus 0.06 mg/kg/day on days -3 to 100 and methotrexate 5 mg/m^2 on days 1, 3, and 7.

Outcomes

Primary Outcome Measures

Progression-free Survival
PFS rate at 1 year.
Overall Survival
OS rate at 1 year.

Secondary Outcome Measures

Full Information

First Posted
July 19, 2005
Last Updated
March 5, 2012
Sponsor
SWOG Cancer Research Network
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00121186
Brief Title
S0501 Fludarabine, Melphalan, and Donor Stem Cell Transplant Followed By Tacrolimus and Methotrexate in Treating Patients for Relapsed Lymphoma
Official Title
Nonmyeloablative Allogeneic Stem Cell Transplantation For Relapsed Hodgkin's or Non-Hodgkin's Lymphoma After Autologous Transplantation ( A BMT Study)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2012
Overall Recruitment Status
Terminated
Why Stopped
poor accrual
Study Start Date
July 2005 (undefined)
Primary Completion Date
January 2008 (Actual)
Study Completion Date
December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
SWOG Cancer Research Network
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and melphalan, before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and methotrexate after transplant may stop this from happening. PURPOSE: This phase II trial is studying how well giving fludarabine together with melphalan followed by tacrolimus and methotrexate works in treating patients who are undergoing a donor stem cell transplant for relapsed lymphoma.
Detailed Description
OBJECTIVES: Determine the 1-year progression-free and overall survival rate in patients with relapsed Hodgkin's or non-Hodgkin's lymphoma after prior autologous stem cell transplantation treated with a nonmyeloablative conditioning regimen comprising fludarabine and melphalan followed by allogeneic bone marrow or peripheral blood stem cell transplantation and immunosuppression comprising tacrolimus and methotrexate. Determine treatment-related mortality in patients treated with this regimen. Determine the toxic effects of this regimen in these patients. Determine engraftment of donor hematopoietic stem cells, as measured by hematopoietic recovery and donor-derived hematopoiesis (determined by T cell and neutrophil specific chimerism) at 2, 3, 6, and 12 months, in patients treated with this regimen. Determine the incidence of acute and chronic graft-versus-host disease in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients are stratified according to diagnosis (Hodgkin's lymphoma vs non-Hodgkin's lymphoma). Patients receive fludarabine IV over 1 hour on days -6 to -2 and melphalan IV over 15-20 minutes on days -3 and -2. Patients undergo allogeneic peripheral blood stem cell or bone marrow transplantation on day 0. Patients receive oral tacrolimus twice daily beginning on day -3 and continuing until day 100 followed by a taper to day 180. Patients also receive methotrexate IV on days 1, 3, and 7. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study transplantation, patients are followed at 1 and 3 months, 1 year, and then annually for up to 4 years. PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within 2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
recurrent adult Hodgkin lymphoma, recurrent small lymphocytic lymphoma, recurrent mantle cell lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse large cell lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Nonmyeloablative allogeneic stem cell transplant
Arm Type
Experimental
Arm Description
Patients are given fludarabine 30 mg/m^2 on days -6 to -2 and melphalan 70 mg/m^2 on days -3 and -2, then transplanted with donor peripheral blood stem cells or harvested bone marrow stem cells on day 0. Patients are then given post-transplant immunosuppression consisting of tacrolimus 0.06 mg/kg/day on days -3 to 100 and methotrexate 5 mg/m^2 on days 1, 3, and 7.
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Intervention Description
30 mg/m^2 on days -6 to -2 (2-6 days before transplant).
Intervention Type
Drug
Intervention Name(s)
melphalan
Intervention Description
70 mg/m^2 on days -3 and -2 (2-3 days before transplant).
Intervention Type
Drug
Intervention Name(s)
methotrexate
Intervention Description
5 mg/m^2 on days 1, 3, and 7 post-transplant.
Intervention Type
Drug
Intervention Name(s)
tacrolimus
Intervention Description
0.03 mg/kg bid on days -3 to 100 post-transplant.
Intervention Type
Procedure
Intervention Name(s)
allogeneic bone marrow transplantation
Intervention Description
if donor bone marrow stem cells are harvested
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Intervention Description
if donor peripheral blood stem cells are harvested
Primary Outcome Measure Information:
Title
Progression-free Survival
Description
PFS rate at 1 year.
Time Frame
1, 3, and 12 months after protocol treatment, then every 3 months for 1 year, every 6 months for year 2, then annually thereafter until 5 years after registration
Title
Overall Survival
Description
OS rate at 1 year.
Time Frame
1, 3, and 12 months after protocol treatment, then every 3 months for 1 year, every 6 months for year 2, then annually thereafter until 5 years after registration

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of lymphoma of 1 of the following types: Diffuse large B-cell lymphoma Follicular lymphoma Grades 1, 2, or 3 Primary mediastinal lymphoma Mantle cell lymphoma Small lymphocytic lymphoma Hodgkin's lymphoma Transformed lymphoma Relapsed after prior autologous bone marrow transplantation (BMT) More than 180 days post BMT Received ≥ 1 course of chemotherapy after BMT relapse Achieved a complete response OR a partial response to chemotherapy Largest residual tumor dimension ≤ 2 cm No clinical or laboratory evidence of CNS involvement by lymphoma HLA-identical donor available, meeting 1 of the following criteria: Sibling donor with 5/6 or 6/6 alleles matching by genotyping No monozygotic identical twins Unrelated donor with 10/10 alleles matching by genotyping PATIENT CHARACTERISTICS: Age 18 and over Performance status Zubrod 0-2 Life expectancy Not specified Hematopoietic Not specified Hepatic Not specified Renal Not specified Cardiovascular LVEF ≥ 40% by MUGA or 2-D echocardiogram (2-D ECHO) No significant cardiac abnormalities by MUGA or 2-D ECHO No uncompensated coronary artery disease by ECG or physical exam None of the following within the past 6 months: Myocardial infarction Unstable angina Uncontrolled atrial fibrillation None of the following within the past 3 months: Severe peripheral vascular disease Venous stasis ulcers Deep venous or arterial thrombosis No uncontrolled hypertension Pulmonary DLCO (corrected) and total lung capacity ≥ 40% of predicted No requirement for continuous supplemental oxygen Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception HIV negative No AIDS No active bacterial, viral, or fungal infection No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix No history of uncontrolled seizures No diabetic ulcers within the past 3 months PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics No more than 1 prior bone marrow transplantation Chemotherapy See Disease Characteristics More than 21 days since prior chemotherapy and recovered Endocrine therapy Not specified Radiotherapy More than 4 weeks since prior radiotherapy Surgery More than 4 weeks since prior major surgery except placement of a venous access device
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick J. Stiff, MD
Organizational Affiliation
Loyola University
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Scott E. Smith, MD, PhD, FACP
Organizational Affiliation
Loyola University
Official's Role
Study Chair
Facility Information:
Facility Name
Cardinal Bernardin Cancer Center at Loyola University Medical Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
St. Francis Hospital and Health Centers - Beech Grove Campus
City
Beech Grove
State/Province
Indiana
ZIP/Postal Code
46107
Country
United States
Facility Name
Reid Hospital & Health Care Services, Incorporated
City
Richmond
State/Province
Indiana
ZIP/Postal Code
47374
Country
United States
Facility Name
Cancer Center of Kansas, PA - Chanute
City
Chanute
State/Province
Kansas
ZIP/Postal Code
66720
Country
United States
Facility Name
Cancer Center of Kansas, PA - Dodge City
City
Dodge City
State/Province
Kansas
ZIP/Postal Code
67801
Country
United States
Facility Name
Cancer Center of Kansas, PA - El Dorado
City
El Dorado
State/Province
Kansas
ZIP/Postal Code
67042
Country
United States
Facility Name
Cancer Center of Kansas, PA - Kingman
City
Kingman
State/Province
Kansas
ZIP/Postal Code
67068
Country
United States
Facility Name
Southwest Medical Center
City
Liberal
State/Province
Kansas
ZIP/Postal Code
67901
Country
United States
Facility Name
Cancer Center of Kansas, PA - Newton
City
Newton
State/Province
Kansas
ZIP/Postal Code
67114
Country
United States
Facility Name
Cancer Center of Kansas, PA - Parsons
City
Parsons
State/Province
Kansas
ZIP/Postal Code
67357
Country
United States
Facility Name
Cancer Center of Kansas, PA - Pratt
City
Pratt
State/Province
Kansas
ZIP/Postal Code
67124
Country
United States
Facility Name
Cancer Center of Kansas, PA - Salina
City
Salina
State/Province
Kansas
ZIP/Postal Code
67042
Country
United States
Facility Name
Cancer Center of Kansas, PA - Wellington
City
Wellington
State/Province
Kansas
ZIP/Postal Code
67152
Country
United States
Facility Name
Associates in Womens Health, PA - North Review
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67203
Country
United States
Facility Name
Cancer Center of Kansas, PA - Medical Arts Tower
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67208
Country
United States
Facility Name
Cancer Center of Kansas, PA - Wichita
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
CCOP - Wichita
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
Via Christi Cancer Center at Via Christi Regional Medical Center
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
Cancer Center of Kansas, PA - Winfield
City
Winfield
State/Province
Kansas
ZIP/Postal Code
67156
Country
United States
Facility Name
Highland Hospital of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14620
Country
United States
Facility Name
Interlakes Oncology/Hematology PC
City
Rochester
State/Province
New York
ZIP/Postal Code
14623
Country
United States
Facility Name
James P. Wilmot Cancer Center at University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Grandview Hospital
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45405
Country
United States
Facility Name
Good Samaritan Hospital
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45406
Country
United States
Facility Name
David L. Rike Cancer Center at Miami Valley Hospital
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45409
Country
United States
Facility Name
Veterans Affairs Medical Center - Dayton
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45428
Country
United States
Facility Name
CCOP - Dayton
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45429
Country
United States
Facility Name
Blanchard Valley Medical Associates
City
Findlay
State/Province
Ohio
ZIP/Postal Code
45840
Country
United States
Facility Name
Charles F. Kettering Memorial Hospital
City
Kettering
State/Province
Ohio
ZIP/Postal Code
45429
Country
United States
Facility Name
Middletown Regional Hospital
City
Middletown
State/Province
Ohio
ZIP/Postal Code
45044
Country
United States
Facility Name
UVMC Cancer Care Center at Upper Valley Medical Center
City
Troy
State/Province
Ohio
ZIP/Postal Code
45373-1300
Country
United States
Facility Name
United States Air Force Medical Center - Wright-Patterson
City
Wright-Patterson Afb
State/Province
Ohio
ZIP/Postal Code
45433-5529
Country
United States
Facility Name
Ruth G. McMillan Cancer Center at Greene Memorial Hospital
City
Xenia
State/Province
Ohio
ZIP/Postal Code
45385
Country
United States

12. IPD Sharing Statement

Learn more about this trial

S0501 Fludarabine, Melphalan, and Donor Stem Cell Transplant Followed By Tacrolimus and Methotrexate in Treating Patients for Relapsed Lymphoma

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