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

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ClinicalTrials.gov Identifier: NCT00121186
Recruitment Status : Terminated (poor accrual)
First Posted : July 21, 2005
Results First Posted : April 3, 2012
Last Update Posted : April 3, 2012
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group

Tracking Information
First Submitted Date  ICMJE July 19, 2005
First Posted Date  ICMJE July 21, 2005
Results First Submitted Date  ICMJE March 5, 2012
Results First Posted Date  ICMJE April 3, 2012
Last Update Posted Date April 3, 2012
Study Start Date  ICMJE July 2005
Actual Primary Completion Date January 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 5, 2012)
  • Progression-free Survival [ 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 ]
    PFS rate at 1 year.
  • Overall Survival [ 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 ]
    OS rate at 1 year.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE S0501 Fludarabine, Melphalan, and Donor Stem Cell Transplant Followed By Tacrolimus and Methotrexate in Treating Patients for Relapsed Lymphoma
Official Title  ICMJE Nonmyeloablative Allogeneic Stem Cell Transplantation For Relapsed Hodgkin's or Non-Hodgkin's Lymphoma After Autologous Transplantation ( A BMT Study)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lymphoma
Intervention  ICMJE
  • Drug: fludarabine phosphate
    30 mg/m^2 on days -6 to -2 (2-6 days before transplant).
  • Drug: melphalan
    70 mg/m^2 on days -3 and -2 (2-3 days before transplant).
  • Drug: methotrexate
    5 mg/m^2 on days 1, 3, and 7 post-transplant.
  • Drug: tacrolimus
    0.03 mg/kg bid on days -3 to 100 post-transplant.
  • Procedure: allogeneic bone marrow transplantation
    if donor bone marrow stem cells are harvested
  • Procedure: peripheral blood stem cell transplantation
    if donor peripheral blood stem cells are harvested
Study Arms  ICMJE Experimental: Nonmyeloablative allogeneic stem cell transplant
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.
Interventions:
  • Drug: fludarabine phosphate
  • Drug: melphalan
  • Drug: methotrexate
  • Drug: tacrolimus
  • Procedure: allogeneic bone marrow transplantation
  • Procedure: peripheral blood stem cell transplantation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 5, 2012)
1
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE December 2011
Actual Primary Completion Date January 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00121186
Other Study ID Numbers  ICMJE CDR0000435930
S0501 ( Other Identifier: SWOG )
U10CA032102 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Southwest Oncology Group
Study Sponsor  ICMJE Southwest Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Patrick J. Stiff, MD Loyola University
Study Chair: Scott E. Smith, MD, PhD, FACP Loyola University
PRS Account Southwest Oncology Group
Verification Date March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP