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
This study is currently recruiting participants.
Verified October 2012 by Fred Hutchinson Cancer Research Center
Sponsor:
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Collaborator:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00112593
First received: June 2, 2005
Last updated: October 2, 2012
Last verified: October 2012
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Purpose
This clinical trial studies 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
| Condition | Intervention | Phase |
|---|---|---|
|
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 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 Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative Blastic Phase Chronic Myelogenous Leukemia Burkitt Lymphoma Childhood Acute Lymphoblastic Leukemia in Remission Childhood Acute Myeloid Leukemia in Remission 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 HIV Infection HIV-associated Hodgkin Lymphoma Intraocular Lymphoma Isolated Plasmacytoma of Bone Juvenile Myelomonocytic Leukemia Mast Cell Leukemia Meningeal Chronic Myelogenous Leukemia Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Nodal Marginal Zone B-cell Lymphoma Noncontiguous Stage II Adult Burkitt Lymphoma Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma Noncontiguous Stage II Adult Lymphoblastic Lymphoma Noncontiguous Stage II Grade 1 Follicular Lymphoma Noncontiguous Stage II Grade 2 Follicular Lymphoma Noncontiguous Stage II Grade 3 Follicular Lymphoma Noncontiguous Stage II Mantle Cell Lymphoma Noncontiguous Stage II Marginal Zone Lymphoma Noncontiguous Stage II Small Lymphocytic Lymphoma Polycythemia Vera Post-transplant Lymphoproliferative Disorder Previously Treated Myelodysplastic Syndromes Primary Central Nervous System Lymphoma Primary Myelofibrosis Primary Systemic Amyloidosis Progressive Hairy Cell Leukemia, Initial Treatment Prolymphocytic Leukemia Secondary Acute Myeloid Leukemia Secondary Myelodysplastic Syndromes Splenic Marginal Zone Lymphoma Stage 0 Chronic Lymphocytic Leukemia Stage I Adult Burkitt Lymphoma Stage I Adult Diffuse Large Cell Lymphoma Stage I Adult Diffuse Mixed Cell Lymphoma Stage I Adult Diffuse Small Cleaved Cell Lymphoma Stage I Adult Hodgkin Lymphoma Stage I Adult Immunoblastic Large Cell Lymphoma Stage I Adult Lymphoblastic Lymphoma Stage I Adult T-cell Leukemia/Lymphoma Stage I Childhood Anaplastic Large Cell Lymphoma Stage I Childhood Hodgkin Lymphoma Stage I Childhood Large Cell Lymphoma Stage I Childhood Lymphoblastic Lymphoma Stage I Childhood Small Noncleaved Cell Lymphoma Stage I Chronic Lymphocytic Leukemia Stage I Cutaneous T-cell Non-Hodgkin Lymphoma Stage I Grade 1 Follicular Lymphoma Stage I Grade 2 Follicular Lymphoma Stage I Grade 3 Follicular Lymphoma Stage I Mantle Cell Lymphoma Stage I Marginal Zone Lymphoma Stage I Multiple Myeloma Stage I Mycosis Fungoides/Sezary Syndrome Stage I Small Lymphocytic Lymphoma Stage II Adult Hodgkin Lymphoma Stage II Adult T-cell Leukemia/Lymphoma Stage II Childhood Anaplastic Large Cell Lymphoma Stage II Childhood Hodgkin Lymphoma Stage II Childhood Large Cell Lymphoma Stage II Childhood Lymphoblastic Lymphoma Stage II Childhood Small Noncleaved Cell Lymphoma Stage II Chronic Lymphocytic Leukemia Stage II Cutaneous T-cell Non-Hodgkin Lymphoma Stage II Multiple Myeloma Stage II Mycosis Fungoides/Sezary Syndrome Stage III Adult Burkitt Lymphoma Stage III Adult Diffuse Large Cell Lymphoma Stage III Adult Diffuse Mixed Cell Lymphoma Stage III Adult Diffuse Small Cleaved Cell Lymphoma Stage III Adult Hodgkin Lymphoma Stage III Adult Immunoblastic Large Cell Lymphoma Stage III Adult Lymphoblastic Lymphoma Stage III Adult T-cell Leukemia/Lymphoma Stage III Childhood Anaplastic Large Cell Lymphoma Stage III Childhood Hodgkin Lymphoma Stage III Childhood Large Cell Lymphoma Stage III Childhood Lymphoblastic Lymphoma Stage III Childhood Small Noncleaved Cell Lymphoma Stage III Chronic Lymphocytic Leukemia Stage III Cutaneous T-cell Non-Hodgkin Lymphoma Stage III Grade 1 Follicular Lymphoma Stage III Grade 2 Follicular Lymphoma Stage III Grade 3 Follicular Lymphoma Stage III Mantle Cell Lymphoma Stage III Marginal Zone Lymphoma Stage III Multiple Myeloma Stage III Mycosis Fungoides/Sezary Syndrome Stage III Small Lymphocytic Lymphoma Stage IV Adult Burkitt Lymphoma Stage IV Adult Diffuse Large Cell Lymphoma Stage IV Adult Diffuse Mixed Cell Lymphoma Stage IV Adult Diffuse Small Cleaved Cell Lymphoma Stage IV Adult Hodgkin Lymphoma Stage IV Adult Immunoblastic Large Cell Lymphoma Stage IV Adult Lymphoblastic Lymphoma Stage IV Adult T-cell Leukemia/Lymphoma Stage IV Childhood Anaplastic Large Cell Lymphoma Stage IV Childhood Hodgkin Lymphoma Stage IV Childhood Large Cell Lymphoma Stage IV Childhood Lymphoblastic Lymphoma Stage IV Childhood Small Noncleaved Cell Lymphoma Stage IV Chronic Lymphocytic Leukemia Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma Stage IV Grade 1 Follicular Lymphoma Stage IV Grade 2 Follicular Lymphoma Stage IV Grade 3 Follicular Lymphoma Stage IV Mantle Cell Lymphoma Stage IV Marginal Zone Lymphoma Stage IV Mycosis Fungoides/Sezary Syndrome Stage IV Small Lymphocytic Lymphoma T-cell Large Granular Lymphocyte Leukemia Unspecified Adult Solid Tumor, Protocol Specific Unspecified Childhood Solid Tumor, Protocol Specific Waldenstrom Macroglobulinemia |
Drug: fludarabine phosphate Drug: cyclosporine Drug: mycophenolate mofetil Procedure: allogeneic bone marrow transplantation Procedure: peripheral blood stem cell transplantation Radiation: total-body irradiation |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
Resource links provided by NLM:
Genetics Home Reference related topics:
complement factor I deficiency
essential thrombocythemia
familial acute myeloid leukemia with mutated CEBPA
PDGFRA-associated chronic eosinophilic leukemia
PDGFRB-associated chronic eosinophilic leukemia
polycythemia vera
primary myelofibrosis
MedlinePlus related topics:
Acute Myeloid Leukemia
Amyloidosis
Bone Marrow Transplantation
Cancer
Chronic Lymphocytic Leukemia
Chronic Myeloid Leukemia
Fungal Infections
HIV/AIDS
Hodgkin Disease
Leukemia
Lymphoma
Multiple Myeloma
Myelodysplastic Syndromes
Drug Information available for:
Mycophenolic acid
Fludarabine
Cyclosporine
Fludarabine phosphate
Mycophenolate mofetil hydrochloride
Mycophenolate mofetil
U.S. FDA Resources
Further study details as provided by Fred Hutchinson Cancer Research Center:
Primary Outcome Measures:
- Death from regimen toxicity or opportunistic infection [ Time Frame: Within the first 100 days ] [ Designated as safety issue: Yes ]
- Death from GVHD [ Time Frame: Within the first 360 days ] [ Designated as safety issue: Yes ]
- Successful induction of mixed hematopoietic chimerism as assessed by the percentage of peripheral blood T cells that are of donor origin [ Time Frame: Days 28, 56, and 80 ] [ Designated as safety issue: No ]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 (OS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Progression of HIV [ Time Frame: Within 1 year ] [ Designated as safety issue: No ]
- Reconstitution of HIV-specific immunity [ Time Frame: 6-12 months ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 20 |
| Study Start Date: | November 1999 |
| Estimated Primary Completion Date: | November 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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:
Drug: cyclosporine
Given IV or PO
Other Names:
Drug: mycophenolate mofetil
Given IV or PO
Other Names:
Procedure: allogeneic bone marrow transplantation
Undergo allogeneic bone marrow or peripheral blood stem cell transplantation
Other Names:
Procedure: peripheral blood stem cell transplantation
Undergo allogeneic bone marrow or peripheral blood stem cell transplantation
Other Names:
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
|
Detailed Description:
PRIMARY OBJECTIVES:
I. To determine the safety of treating high-risk HIV1-infected patients with 200 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 CD3) 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.
Eligibility| Ages Eligible for Study: | up to 75 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00112593
Locations
| United States, Washington | |
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Recruiting |
| Seattle, Washington, United States, 98109 | |
| Contact: Ann E. Woolfrey 206-667-4453 | |
| Principal Investigator: Ann E. Woolfrey | |
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Investigators
| Principal Investigator: | Ann Woolfrey | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium |
More Information
No publications provided by Fred Hutchinson Cancer Research Center
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Woolfrey, Ann, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium |
| ClinicalTrials.gov Identifier: | NCT00112593 History of Changes |
| Other Study ID Numbers: | 1410.00, NCI-2010-00802, P01CA018029 |
| Study First Received: | June 2, 2005 |
| Last Updated: | October 2, 2012 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Fred Hutchinson Cancer Research Center:
|
HIV; Lymphoma; Leukemia |
Additional relevant MeSH terms:
|
Congenital Abnormalities Acquired Immunodeficiency Syndrome HIV Infections Primary Myelofibrosis Amyloidosis Blast Crisis Burkitt Lymphoma Neoplasms Hodgkin Disease Immunoblastic Lymphadenopathy Leukemia Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Hairy Cell Leukemia, Lymphoid Precursor Cell Lymphoblastic Leukemia-Lymphoma |
Leukemia, Mast-Cell Leukemia, Myeloid, Acute Leukemia, Myeloid Leukemia, Myeloid, Accelerated Phase Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid, Chronic-Phase Leukemia, Myelomonocytic, Chronic Leukemia, Neutrophilic, Chronic Leukemia, Prolymphocytic Leukemia, T-Cell Leukemia-Lymphoma, Adult T-Cell Lymphoma Lymphoma, Follicular Lymphoma, Non-Hodgkin Lymphomatoid Granulomatosis |
ClinicalTrials.gov processed this record on February 21, 2013
