Fludarabine and Total-Body Irradiation Followed By Donor Stem Cell Transplant and Cyclosporine and Mycophenolate Mofetil in Treating HIV-Positive Patients With or Without Cancer
Allogeneic Hematopoietic Stem Cell Transplantation for Induction of Mixed Hematopoietic Chimerism in Patients Infected With Human Immunodeficiency Virus-1 Using a Non-Marrow Ablative Conditioning Regimen Containing Total Body Irradiation in Combination With Post-Transplant Immunosuppression With Cyclosporine and Mycophenolate Mofetil
4 other identifiers
interventional
5
1 country
1
Brief Summary
This clinical trial studies the side effects and best dose of giving fludarabine and total-body irradiation (TBI) together followed by a donor stem cell transplant and cyclosporine and mycophenolate mofetil in treating human immunodeficiency virus (HIV)-positive patients with or without cancer. Giving low doses of chemotherapy, such as fludarabine, and TBI before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer or abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells 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 cyclosporine (CSP) and mycophenolate mofetil (MMF) after the transplant may stop this from happening.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 1, 1999
CompletedFirst Submitted
Initial submission to the registry
June 2, 2005
CompletedFirst Posted
Study publicly available on registry
June 3, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2014
CompletedResults Posted
Study results publicly available
May 24, 2017
CompletedMay 24, 2017
April 1, 2017
15 years
June 2, 2005
April 17, 2017
April 17, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Death From Regimen Toxicity or Opportunistic Infection
Within the first 100 days
Death From GVHD
Within the first 360 days
Successful Induction of Mixed Hematopoietic Chimerism as Assessed by the Percentage of Peripheral Blood T Cells That Are of Donor Origin
Determined by a DNA-based assay that compares the profile of amplified fragment length polymorphisms (ampFLP) of the patient and donor.
Up to day 80
Secondary Outcomes (3)
Overall Survival
Up to 1 year
Progression of HIV
Within 1 year
Reconstitution of HIV-specific Immunity
Up to 1 year
Study Arms (1)
Treatment (allogeneic hematopoietic stem cell transplantation)
EXPERIMENTALCONDITIONING REGIMEN: Patients receive fludarabine IV over 2 hours on days -4, -3, and -2. Patients undergo TBI on day 0. TRANSPLANTATION: After completion of TBI, patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine IV or PO 2 to 3 times daily on days -3 to 99 with taper beginning on day 100 and continuing until day 177 in the absence of GVHD. Beginning within 6 hours after transplantation, patients also receive mycophenolate mofetil IV or PO 3 times daily on days 0 to 40 followed by a taper in the absence of GVHD.
Interventions
Given IV
Undergo TBI
Undergo allogeneic bone marrow or peripheral blood stem cell transplantation
Given IV or PO
Given IV or PO
Correlative studies
Eligibility Criteria
You may qualify if:
- Patients with hematologic malignancy, lymphoma or other HIV-associated malignancy are eligible provided these criteria are met:
- The malignancy is in complete remission or very good partial remission, defined as a significant reduction of disease with therapy and no evidence for continued tumor growth in the case of lymphoma or solid tumors
- Highly active antiretroviral therapy (HAART) is initiated within one month of hematopoietic cell transplant
- Viral load has decreased by \>= 1.5 logs or viral load \< 5000 copies/ml plasma on HAART therapy
- CD4 count is allowed to be \> 100 cells/ul
- HIV infected patients without malignancy who have failed HAART are eligible provided that these criteria are met:
- They have been treated with more than one regimen of HAART for a total of at least 6 months duration
- The viral load is \< 50 copies/ml plasma
- The CD4 count \< 100 cells/ul
- DONOR: Human leukocyte antigen (HLA) genotypically/phenotypically identical donor; if more than one HLA-identical sibling is available, priority will be given to donors matched for cytomegalovirus (CMV) status, ABO titer, and sex
- Peripheral blood stem cells will be collected from donors greater than 12 years of age
- Bone marrow will be collected from donors less than 12 years of age
- DONOR: HLA phenotypically identical unrelated donor; match grades allowed:
- Match grade 1: Matched at allele level for HLA-A, B, C, DRB1, and DQB1
- Match grade 2.1: Single allele disparity for HLA-A, B, C, DRB1, and DQB1
You may not qualify if:
- Positive serology for toxoplasma gondii on treatment or with evidence of active infection
- Patients with other disease or organ dysfunction that would limit survival to less than 30 days
- Patients with medical history of noncompliance with HAART or medical therapy
- DONOR: Donors for whom medical or psychologic reasons would make donor procedure intolerable
- DONOR: Marrow donors who have increased anesthetic risk
- DONOR: Donors who are HIV positive
- DONOR: Age \> 75 years
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Fred Hutchinson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
Related Publications (1)
Woolfrey AE, Malhotra U, Harrington RD, McNevin J, Manley TJ, Riddell SR, Coombs RW, Appelbaum FR, Corey L, Storb R. Generation of HIV-1-specific CD8+ cell responses following allogeneic hematopoietic cell transplantation. Blood. 2008 Oct 15;112(8):3484-7. doi: 10.1182/blood-2008-05-157511. Epub 2008 Aug 12.
PMID: 18698002DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Ann Woolfrey, MD
- Organization
- Fred Hutchinson Cancer Research Center
Study Officials
- PRINCIPAL INVESTIGATOR
Ann Woolfrey
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
June 2, 2005
First Posted
June 3, 2005
Study Start
November 1, 1999
Primary Completion
November 1, 2014
Last Updated
May 24, 2017
Results First Posted
May 24, 2017
Record last verified: 2017-04