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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00112593
Recruitment Status : Completed
First Posted : June 3, 2005
Results First Posted : May 24, 2017
Last Update Posted : May 24, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Ann Woolfrey, Fred Hutchinson Cancer Center

Study Description
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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.

Condition or disease Intervention/treatment 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 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 Hepatosplenic T-cell Lymphoma 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 Myeloid/NK-cell Acute Leukemia 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 Noncutaneous Extranodal Lymphoma Peripheral T-cell 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 Small Intestine Lymphoma 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 Small Lymphocytic Lymphoma Stage IA Mycosis Fungoides/Sezary Syndrome Stage IB Mycosis Fungoides/Sezary Syndrome 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 IIA Mycosis Fungoides/Sezary Syndrome Stage IIB 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 Small Lymphocytic Lymphoma Stage IIIA Mycosis Fungoides/Sezary Syndrome Stage IIIB Mycosis Fungoides/Sezary Syndrome 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 Small Lymphocytic Lymphoma Stage IVA Mycosis Fungoides/Sezary Syndrome Stage IVB Mycosis Fungoides/Sezary Syndrome T-cell Large Granular Lymphocyte Leukemia Testicular Lymphoma Unspecified Adult Solid Tumor, Protocol Specific Unspecified Childhood Solid Tumor, Protocol Specific Waldenström Macroglobulinemia Drug: fludarabine phosphate Radiation: total-body irradiation Procedure: peripheral blood stem cell transplantation Drug: cyclosporine Drug: mycophenolate mofetil Other: laboratory biomarker analysis Not Applicable

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : November 1999
Actual Primary Completion Date : November 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Genetic and Rare Diseases Information Center resources: Acute Lymphoblastic Leukemia Lymphoblastic Lymphoma Childhood Acute Lymphoblastic Leukemia Myeloid Leukemia Chronic Myeloid Leukemia Multiple Myeloma Chronic Lymphocytic Leukemia Lymphosarcoma B-cell Lymphoma Myelodysplastic Syndromes Mycosis Fungoides Acute Myeloid Leukemia Acute Non Lymphoblastic Leukemia Mantle Cell Lymphoma Diffuse Large B-Cell Lymphoma Chronic Myelomonocytic Leukemia Juvenile Myelomonocytic Leukemia Peripheral T-cell Lymphoma Extranodal Nasal NK/T Cell Lymphoma Primary Central Nervous System Lymphoma Primary Myelofibrosis Polycythemia Vera Chronic Myeloproliferative Disorders Cutaneous T-cell Lymphoma Follicular Lymphoma Hodgkin Lymphoma Chronic Graft Versus Host Disease Acute Graft Versus Host Disease Essential Thrombocythemia Burkitt Lymphoma Plasmablastic Lymphoma Lymphoma, Large-cell, Immunoblastic Hairy Cell Leukemia Sezary Syndrome Adult T-cell Leukemia/lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Angioimmunoblastic Lymphadenopathy With Dysproteinemia Waldenstrom Macroglobulinemia Plasmacytoma Aggressive NK Cell Leukemia T-cell Large Granular Lymphocyte Leukemia Marginal Zone Lymphoma Myelodysplastic/myeloproliferative Disease AL Amyloidosis Chronic Neutrophilic Leukemia Post-transplant Lymphoproliferative Disease Leukemia, T-cell, Chronic Lymphomatoid Granulomatosis Hypereosinophilic Syndrome Mastocytosis

Arms and Interventions
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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:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara

Radiation: total-body irradiation
Undergo TBI
Other Name: TBI

Procedure: peripheral blood stem cell transplantation
Undergo allogeneic bone marrow or peripheral blood stem cell transplantation
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell

Drug: cyclosporine
Given IV or PO
Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune

Drug: mycophenolate mofetil
Given IV or PO
Other Names:
  • Cellcept
  • MMF

Other: laboratory biomarker analysis
Correlative studies


Outcome Measures
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Primary Outcome Measures :
  1. Death From Regimen Toxicity or Opportunistic Infection [ Time Frame: Within the first 100 days ]
  2. Death From GVHD [ Time Frame: Within the first 360 days ]
  3. Successful Induction of Mixed Hematopoietic Chimerism as Assessed by the Percentage of Peripheral Blood T Cells That Are of Donor Origin [ Time Frame: 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 :
  1. Overall Survival [ Time Frame: Up to 1 year ]
    Kaplan-Meier estimate assessed at 1 year.

  2. Progression of HIV [ Time Frame: Within 1 year ]
    Count of participants with HIV progression.

  3. Reconstitution of HIV-specific Immunity [ Time Frame: Up to 1 year ]

Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00112593


Locations
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United States, Washington
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
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Principal Investigator: Ann Woolfrey Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Ann Woolfrey, Principal Investigator, Fred Hutchinson Cancer Center
ClinicalTrials.gov Identifier: NCT00112593    
Obsolete Identifiers: NCT00010348
Other Study ID Numbers: 1410.00
NCI-2010-00802 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
1410.00 ( Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
P01CA018029 ( U.S. NIH Grant/Contract )
First Posted: June 3, 2005    Key Record Dates
Results First Posted: May 24, 2017
Last Update Posted: May 24, 2017
Last Verified: April 2017
Keywords provided by Ann Woolfrey, Fred Hutchinson Cancer Center:
HIV
Lymphoma
Leukemia
Additional relevant MeSH terms:
Layout table for MeSH terms
Burkitt Lymphoma
Mycoses
Lymphoma
Leukemia
Leukemia, Myeloid
Multiple Myeloma
Neoplasms, Plasma Cell
Leukemia, Myeloid, Acute
Lymphoma, Follicular
Preleukemia
Lymphoma, Non-Hodgkin
Neoplasm Metastasis
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoma, B-Cell
 Leukemia, Lymphocytic, Chronic, B-Cell
Hodgkin Disease
Lymphoma, Mantle-Cell
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphoma, B-Cell, Marginal Zone
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Plasmablastic Lymphoma
Mycosis Fungoides
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Sezary Syndrome
Leukemia, T-Cell