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

This study has been terminated.
(poor accrual)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00121186
First received: July 19, 2005
Last updated: March 5, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Lymphoma
Drug: fludarabine phosphate
Drug: melphalan
Drug: methotrexate
Drug: tacrolimus
Procedure: allogeneic bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Nonmyeloablative Allogeneic Stem Cell Transplantation For Relapsed Hodgkin's or Non-Hodgkin's Lymphoma After Autologous Transplantation ( A BMT Study)

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    OS rate at 1 year.


Enrollment: 1
Study Start Date: July 2005
Study Completion Date: December 2011
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00121186

Locations
United States, Illinois
Cardinal Bernardin Cancer Center at Loyola University Medical Center
Maywood, Illinois, United States, 60153
United States, Indiana
St. Francis Hospital and Health Centers - Beech Grove Campus
Beech Grove, Indiana, United States, 46107
Reid Hospital & Health Care Services, Incorporated
Richmond, Indiana, United States, 47374
United States, Kansas
Cancer Center of Kansas, PA - Chanute
Chanute, Kansas, United States, 66720
Cancer Center of Kansas, PA - Dodge City
Dodge City, Kansas, United States, 67801
Cancer Center of Kansas, PA - El Dorado
El Dorado, Kansas, United States, 67042
Cancer Center of Kansas, PA - Kingman
Kingman, Kansas, United States, 67068
Southwest Medical Center
Liberal, Kansas, United States, 67901
Cancer Center of Kansas, PA - Newton
Newton, Kansas, United States, 67114
Cancer Center of Kansas, PA - Parsons
Parsons, Kansas, United States, 67357
Cancer Center of Kansas, PA - Pratt
Pratt, Kansas, United States, 67124
Cancer Center of Kansas, PA - Salina
Salina, Kansas, United States, 67042
Cancer Center of Kansas, PA - Wellington
Wellington, Kansas, United States, 67152
Cancer Center of Kansas, PA - Wichita
Wichita, Kansas, United States, 67214
Via Christi Cancer Center at Via Christi Regional Medical Center
Wichita, Kansas, United States, 67214
Associates in Womens Health, PA - North Review
Wichita, Kansas, United States, 67203
CCOP - Wichita
Wichita, Kansas, United States, 67214
Cancer Center of Kansas, PA - Medical Arts Tower
Wichita, Kansas, United States, 67208
Cancer Center of Kansas, PA - Winfield
Winfield, Kansas, United States, 67156
United States, New York
Highland Hospital of Rochester
Rochester, New York, United States, 14620
Interlakes Oncology/Hematology PC
Rochester, New York, United States, 14623
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, Ohio
Good Samaritan Hospital
Dayton, Ohio, United States, 45406
CCOP - Dayton
Dayton, Ohio, United States, 45429
Veterans Affairs Medical Center - Dayton
Dayton, Ohio, United States, 45428
David L. Rike Cancer Center at Miami Valley Hospital
Dayton, Ohio, United States, 45409
Grandview Hospital
Dayton, Ohio, United States, 45405
Blanchard Valley Medical Associates
Findlay, Ohio, United States, 45840
Charles F. Kettering Memorial Hospital
Kettering, Ohio, United States, 45429
Middletown Regional Hospital
Middletown, Ohio, United States, 45044
UVMC Cancer Care Center at Upper Valley Medical Center
Troy, Ohio, United States, 45373-1300
United States Air Force Medical Center - Wright-Patterson
Wright-Patterson Afb, Ohio, United States, 45433-5529
Ruth G. McMillan Cancer Center at Greene Memorial Hospital
Xenia, Ohio, United States, 45385
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Study Chair: Patrick J. Stiff, MD Loyola University
Study Chair: Scott E. Smith, MD, PhD, FACP Loyola University
  More Information

No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00121186     History of Changes
Other Study ID Numbers: CDR0000435930, S0501, U10CA032102
Study First Received: July 19, 2005
Results First Received: March 5, 2012
Last Updated: March 5, 2012
Health Authority: United States: Federal Government

Keywords provided by Southwest Oncology Group:
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

Additional relevant MeSH terms:
Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Fludarabine
Fludarabine phosphate
Melphalan
Methotrexate
Tacrolimus
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014