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

Lymphoma Clinical Trial

Official title:

Nonmyeloablative Allogeneic Stem Cell Transplantation For Relapsed Hodgkin's or Non-Hodgkin's Lymphoma After Autologous Transplantation ( A BMT Study)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00121186
• Other study ID #: CDR0000435930
• Secondary ID: S0501U10CA032102
• Status: Terminated
• Phase: Phase 2
• First received: July 19, 2005
• Last updated: March 5, 2012
• Start date: July 2005
• Est. completion date: December 2011

Study information

• Verified date: March 2012
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: December 2011
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma

Intervention

Drug:
• fludarabine phosphate
30 mg/m^2 on days -6 to -2 (2-6 days before transplant).
• melphalan
70 mg/m^2 on days -3 and -2 (2-3 days before transplant).
• methotrexate
5 mg/m^2 on days 1, 3, and 7 post-transplant.
• 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
• peripheral blood stem cell transplantation
if donor peripheral blood stem cells are harvested

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival	PFS rate at 1 year.	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	No
Primary	Overall Survival	OS rate at 1 year.	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	No