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

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

Tracking Information

• First Submitted Date: July 19, 2005
• First Posted Date: July 21, 2005
• Results First Submitted Date: March 5, 2012
• Results First Posted Date: April 3, 2012
• Last Update Posted Date: April 3, 2012
• Study Start Date: July 2005
• Actual Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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)

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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lymphoma

Intervention

• 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

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

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: March 5, 2012): 1
• Original Enrollment: Not Provided
• Actual Study Completion Date: December 2011
• Actual Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00121186
• Other Study ID Numbers: 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: Not Provided
• Responsible Party: Southwest Oncology Group
• Study Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)

Investigators

• 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