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
Study Details
Study Description
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.
Detailed Description
PRIMARY OBJECTIVES:
-
To determine the safety of treating high-risk HIV1-infected patients with 200 centigray (cGy) TBI plus post-transplant MMF/CSP.
-
To determine whether 200 cGy TBI plus post-transplant MMF/CSP results in stable mixed donor lymphocyte chimerism (5-95% donor cluster of differentiation [CD]3) in high-risk human immunodeficiency virus (HIV)-1 infected patients.
SECONDARY OBJECTIVES:
-
To define the kinetics of immune reconstitution following a non-lethal conditioning regimen in HIV1-infected patients.
-
To determine the effect of a non-lethal conditioning regimen on viral load.
OUTLINE:
CONDITIONING REGIMEN: Patients receive fludarabine intravenously (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 orally (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 graft-vs-host disease (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.
After completion of study treatment, patients are followed up for at least 1 year.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment (allogeneic hematopoietic stem cell transplantation) CONDITIONING 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. |
Drug: fludarabine phosphate
Given IV
Other Names:
Radiation: total-body irradiation
Undergo TBI
Other Names:
Procedure: peripheral blood stem cell transplantation
Undergo allogeneic bone marrow or peripheral blood stem cell transplantation
Other Names:
Drug: cyclosporine
Given IV or PO
Other Names:
Drug: mycophenolate mofetil
Given IV or PO
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
Outcome Measures
Primary Outcome Measures
- 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 [Up to day 80]
Determined by a DNA-based assay that compares the profile of amplified fragment length polymorphisms (ampFLP) of the patient and donor.
Secondary Outcome Measures
- Overall Survival [Up to 1 year]
Kaplan-Meier estimate assessed at 1 year.
- Progression of HIV [Within 1 year]
Count of participants with HIV progression.
- Reconstitution of HIV-specific Immunity [Up to 1 year]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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
Exclusion Criteria:
-
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle | Washington | United States | 98109 |
Sponsors and Collaborators
- Fred Hutchinson Cancer Center
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Ann Woolfrey, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 1410.00
- NCI-2010-00802
- 1410.00
- P30CA015704
- P01CA018029
- NCT00010348
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Treatment (Allogeneic Hematopoietic Stem Cell Transplantation) |
|---|---|
| Arm/Group Description | CONDITIONING 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. fludarabine phosphate: Given IV total-body irradiation: Undergo TBI peripheral blood stem cell transplantation: Undergo allogeneic bone marrow or peripheral blood stem cell transplantation cyclosporine: Given IV or PO mycophenolate mofetil: Given IV or PO laboratory biomarker analysis: Correlative studies |
| Period Title: Overall Study | |
| STARTED | 5 |
| COMPLETED | 5 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Treatment (Allogeneic Hematopoietic Stem Cell Transplantation) |
|---|---|
| Arm/Group Description | CONDITIONING 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. fludarabine phosphate: Given IV total-body irradiation: Undergo TBI peripheral blood stem cell transplantation: Undergo allogeneic bone marrow or peripheral blood stem cell transplantation cyclosporine: Given IV or PO mycophenolate mofetil: Given IV or PO laboratory biomarker analysis: Correlative studies |
| Overall Participants | 5 |
| Age (years) [Mean (Full Range) ] | |
| Mean (Full Range) [years] |
43
|
| Sex: Female, Male (Count of Participants) | |
| Female |
0
0%
|
| Male |
5
100%
|
Outcome Measures
| Title | Death From Regimen Toxicity or Opportunistic Infection |
|---|---|
| Description | |
| Time Frame | Within the first 100 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Treatment (Allogeneic Hematopoietic Stem Cell Transplantation) |
|---|---|
| Arm/Group Description | CONDITIONING 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. fludarabine phosphate: Given IV total-body irradiation: Undergo TBI peripheral blood stem cell transplantation: Undergo allogeneic bone marrow or peripheral blood stem cell transplantation cyclosporine: Given IV or PO mycophenolate mofetil: Given IV or PO laboratory biomarker analysis: Correlative studies |
| Measure Participants | 5 |
| Count of Participants [Participants] |
0
0%
|
| Title | Death From GVHD |
|---|---|
| Description | |
| Time Frame | Within the first 360 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Treatment (Allogeneic Hematopoietic Stem Cell Transplantation) |
|---|---|
| Arm/Group Description | CONDITIONING 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. fludarabine phosphate: Given IV total-body irradiation: Undergo TBI peripheral blood stem cell transplantation: Undergo allogeneic bone marrow or peripheral blood stem cell transplantation cyclosporine: Given IV or PO mycophenolate mofetil: Given IV or PO laboratory biomarker analysis: Correlative studies |
| Measure Participants | 5 |
| Count of Participants [Participants] |
0
0%
|
| Title | Successful Induction of Mixed Hematopoietic Chimerism as Assessed by the Percentage of Peripheral Blood T Cells That Are of Donor Origin |
|---|---|
| Description | Determined by a DNA-based assay that compares the profile of amplified fragment length polymorphisms (ampFLP) of the patient and donor. |
| Time Frame | Up to day 80 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Treatment (Allogeneic Hematopoietic Stem Cell Transplantation) |
|---|---|
| Arm/Group Description | CONDITIONING 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. fludarabine phosphate: Given IV total-body irradiation: Undergo TBI peripheral blood stem cell transplantation: Undergo allogeneic bone marrow or peripheral blood stem cell transplantation cyclosporine: Given IV or PO mycophenolate mofetil: Given IV or PO laboratory biomarker analysis: Correlative studies |
| Measure Participants | 5 |
| Count of Participants [Participants] |
5
100%
|
| Title | Overall Survival |
|---|---|
| Description | Kaplan-Meier estimate assessed at 1 year. |
| Time Frame | Up to 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Treatment (Allogeneic Hematopoietic Stem Cell Transplantation) |
|---|---|
| Arm/Group Description | CONDITIONING 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. fludarabine phosphate: Given IV total-body irradiation: Undergo TBI peripheral blood stem cell transplantation: Undergo allogeneic bone marrow or peripheral blood stem cell transplantation cyclosporine: Given IV or PO mycophenolate mofetil: Given IV or PO laboratory biomarker analysis: Correlative studies |
| Measure Participants | 5 |
| Number (95% Confidence Interval) [survival probability] |
0.40
|
| Title | Progression of HIV |
|---|---|
| Description | Count of participants with HIV progression. |
| Time Frame | Within 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Treatment (Allogeneic Hematopoietic Stem Cell Transplantation) |
|---|---|
| Arm/Group Description | CONDITIONING 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. fludarabine phosphate: Given IV total-body irradiation: Undergo TBI peripheral blood stem cell transplantation: Undergo allogeneic bone marrow or peripheral blood stem cell transplantation cyclosporine: Given IV or PO mycophenolate mofetil: Given IV or PO laboratory biomarker analysis: Correlative studies |
| Measure Participants | 5 |
| Count of Participants [Participants] |
0
0%
|
| Title | Reconstitution of HIV-specific Immunity |
|---|---|
| Description | |
| Time Frame | Up to 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Treatment (Allogeneic Hematopoietic Stem Cell Transplantation) |
|---|---|
| Arm/Group Description | CONDITIONING 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. fludarabine phosphate: Given IV total-body irradiation: Undergo TBI peripheral blood stem cell transplantation: Undergo allogeneic bone marrow or peripheral blood stem cell transplantation cyclosporine: Given IV or PO mycophenolate mofetil: Given IV or PO laboratory biomarker analysis: Correlative studies |
| Measure Participants | 4 |
| Count of Participants [Participants] |
2
40%
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Treatment (Allogeneic Hematopoietic Stem Cell Transplantation) | |
| Arm/Group Description | CONDITIONING 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. fludarabine phosphate: Given IV total-body irradiation: Undergo TBI peripheral blood stem cell transplantation: Undergo allogeneic bone marrow or peripheral blood stem cell transplantation cyclosporine: Given IV or PO mycophenolate mofetil: Given IV or PO laboratory biomarker analysis: Correlative studies | |
All Cause Mortality |
||
| Treatment (Allogeneic Hematopoietic Stem Cell Transplantation) | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Treatment (Allogeneic Hematopoietic Stem Cell Transplantation) | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/5 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Treatment (Allogeneic Hematopoietic Stem Cell Transplantation) | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/5 (0%) | |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE 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.
Results Point of Contact
| Name/Title | Ann Woolfrey, MD |
|---|---|
| Organization | Fred Hutchinson Cancer Research Center |
| Phone | 206-667-4453 |
| awoolfre@fredhutch.org |
- 1410.00
- NCI-2010-00802
- 1410.00
- P30CA015704
- P01CA018029
- NCT00010348