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

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00121186
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 1
• Locations: 33
• Arm: 1
• Duration (Months): 77
• Patients Per Site: 0
• Patients Per Site Per Month: 0

Study Details

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.

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

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 Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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)
• Study Start Date: Jul 1, 2005
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival [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.

2. Overall Survival [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois	United States	60153
2	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
3	Reid Hospital & Health Care Services, Incorporated	Richmond	Indiana	United States	47374
4	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
5	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
6	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
7	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
8	Southwest Medical Center	Liberal	Kansas	United States	67901
9	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
10	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
11	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
12	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67042
13	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
14	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67203
15	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
16	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
17	CCOP - Wichita	Wichita	Kansas	United States	67214
18	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
19	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
20	Highland Hospital of Rochester	Rochester	New York	United States	14620
21	Interlakes Oncology/Hematology PC	Rochester	New York	United States	14623
22	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
23	Grandview Hospital	Dayton	Ohio	United States	45405
24	Good Samaritan Hospital	Dayton	Ohio	United States	45406
25	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
26	Veterans Affairs Medical Center - Dayton	Dayton	Ohio	United States	45428
27	CCOP - Dayton	Dayton	Ohio	United States	45429
28	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
29	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
30	Middletown Regional Hospital	Middletown	Ohio	United States	45044
31	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
32	United States Air Force Medical Center - Wright-Patterson	Wright-Patterson Afb	Ohio	United States	45433-5529
33	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Patrick J. Stiff, MD, Loyola University
• Study Chair: Scott E. Smith, MD, PhD, FACP, Loyola University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00121186
• Other Study ID Numbers: CDR0000435930; S0501; U10CA032102
• First Posted: Jul 21, 2005
• Last Update Posted: Apr 3, 2012
• Last Verified: Mar 1, 2012

• 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; Methotrexate; Fludarabine phosphate; Fludarabine; Melphalan; Tacrolimus

Study Results

Participant Flow

Arm/Group Title	Nonmyeloablative Allogeneic Stem Cell Transplant
Arm/Group 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.
Period Title: Overall Study
STARTED	1
COMPLETED	1
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Nonmyeloablative Allogeneic Stem Cell Transplant
Arm/Group 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.
Overall Participants	1
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	47.2
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	1 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	1 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	1 100%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nonmyeloablative Allogeneic Stem Cell Transplant
Arm/Group 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.
Measure Participants	1
Number [participants]	1 100%

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nonmyeloablative Allogeneic Stem Cell Transplant
Arm/Group 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.
Measure Participants	1
Number [participants]	1 100%

Adverse Events

Time Frame	After transplant, and after every month of protocol treatment, for a maximum of 6 months
Arm/Group Title	Nonmyeloablative Allogeneic Stem Cell Transplant
Arm/Group Description
All Cause Mortality
	Nonmyeloablative Allogeneic Stem Cell Transplant
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Nonmyeloablative Allogeneic Stem Cell Transplant
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	Nonmyeloablative Allogeneic Stem Cell Transplant
	Affected / at Risk (%)	# Events
Total	1/1 (100%)
Blood and lymphatic system disorders
Hemoglobin	1/1 (100%)
Eye disorders
Dry eye syndrome	1/1 (100%)
Gastrointestinal disorders
Diarrhea	1/1 (100%)
Nausea	1/1 (100%)
General disorders
Fatigue (asthenia, lethargy, malaise)	1/1 (100%)
Investigations
Leukocytes (total WBC)	1/1 (100%)
Lymphopenia	1/1 (100%)
Neutrophils/granulocytes (ANC/AGC)	1/1 (100%)
Platelets	1/1 (100%)
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	1/1 (100%)
Skin and subcutaneous tissue disorders
Dry skin	1/1 (100%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.