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
Official Title
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
Acronym
Not provided
Organization
Fred Hutchinson Cancer CenterOTHER
Status Module
Record Verification Date
Apr 2017
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Nov 1999
Primary Completion Date
Nov 2014Actual
Completion Date
Not provided
First Submitted Date
Jun 2, 2005
First Submission Date that Met QC Criteria
Jun 2, 2005
First Posted Date
Jun 3, 2005Estimated
Results Waived
Not provided
Results First Submitted Date
Apr 17, 2017
Results First Submitted that Met QC Criteria
Apr 17, 2017
Results First Posted Date
May 24, 2017Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Apr 17, 2017
Last Update Posted Date
May 24, 2017Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Ann Woolfrey, Principal Investigator, Fred Hutchinson Cancer CenterPrincipal Investigator
Lead Sponsor
Fred Hutchinson Cancer CenterOTHER
Collaborators
Name
Class
National Cancer Institute (NCI)
NIH
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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:
I. To determine the safety of treating high-risk HIV1-infected patients with 200 centigray (cGy) TBI plus post-transplant MMF/CSP.
II. 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:
I. To define the kinetics of immune reconstitution following a non-lethal conditioning regimen in HIV1-infected patients.
II. 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.
Conditions Module
Conditions
Accelerated Phase Chronic Myelogenous Leukemia
Acute Undifferentiated Leukemia
Adult Acute Lymphoblastic Leukemia in Remission
Adult Acute Myeloid Leukemia in Remission
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Adult Grade III Lymphomatoid Granulomatosis
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Aggressive NK-cell Leukemia
AIDS-related Diffuse Large Cell Lymphoma
AIDS-related Diffuse Mixed Cell Lymphoma
AIDS-related Diffuse Small Cleaved Cell Lymphoma
AIDS-related Immunoblastic Large Cell Lymphoma
AIDS-related Lymphoblastic Lymphoma
AIDS-related Peripheral/Systemic Lymphoma
AIDS-related Primary CNS Lymphoma
AIDS-related Small Noncleaved Cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Blastic Phase Chronic Myelogenous Leukemia
Childhood Acute Lymphoblastic Leukemia in Remission
Childhood Acute Myeloid Leukemia in Remission
Childhood Burkitt Lymphoma
Childhood Chronic Myelogenous Leukemia
Childhood Diffuse Large Cell Lymphoma
Childhood Grade III Lymphomatoid Granulomatosis
Childhood Immunoblastic Large Cell Lymphoma
Childhood Myelodysplastic Syndromes
Childhood Nasal Type Extranodal NK/T-cell Lymphoma
Chronic Eosinophilic Leukemia
Chronic Myelomonocytic Leukemia
Chronic Neutrophilic Leukemia
Chronic Phase Chronic Myelogenous Leukemia
Contiguous Stage II Adult Burkitt Lymphoma
Contiguous Stage II Adult Diffuse Large Cell Lymphoma
Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma
Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma
Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma
Contiguous Stage II Adult Lymphoblastic Lymphoma
Contiguous Stage II Grade 1 Follicular Lymphoma
Contiguous Stage II Grade 2 Follicular Lymphoma
Contiguous Stage II Grade 3 Follicular Lymphoma
Contiguous Stage II Mantle Cell Lymphoma
Contiguous Stage II Marginal Zone Lymphoma
Contiguous Stage II Small Lymphocytic Lymphoma
Cutaneous B-cell Non-Hodgkin Lymphoma
Essential Thrombocythemia
Extramedullary Plasmacytoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
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.
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
Measure
Description
Time Frame
Overall Survival
Kaplan-Meier estimate assessed at 1 year.
Up to 1 year
Progression of HIV
Count of participants with HIV progression.
Other Outcomes
Not provided
Eligibility Module
Eligibility 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
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
Not provided
Maximum Age
75 Years
Standard Ages
ChildAdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Ann Woolfrey
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Principal Investigator
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
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
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
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
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
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
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
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
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
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