Skip to main content
OpenTrials
Completed

NCT Number: NCT00112593

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 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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Accelerated Phase Chronic Myelogenous 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 Acute Undifferentiated Leukemia Adult Acute Lymphoblastic 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 Acute Myeloid Leukemia in Remission Adult Grade III Lymphomatoid Granulomatosis Adult Nasal Type Extranodal NK/T-cell Lymphoma Aggressive NK-cell Leukemia Amyloidosis Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Blast Crisis Blastic Phase Chronic Myelogenous Leukemia Blood Coagulation Disorders Blood Platelet Disorders Blood Protein Disorders Blood-Borne Infections Bone Marrow Diseases Bone Marrow Neoplasms Burkitt Lymphoma Carcinogenesis Cardiovascular Diseases Cell Transformation, Neoplastic 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 Disease Chronic Eosinophilic Leukemia Chronic Myelomonocytic Leukemia Chronic Neutrophilic Leukemia Chronic Phase Chronic Myelogenous Leukemia Communicable Diseases Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities 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 DNA Virus Infections Dendritic Cell Sarcoma, Interdigitating Disease Attributes Epstein-Barr Virus Infections Essential Thrombocythemia Extramedullary Plasmacytoma Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Eye Neoplasms Genital Diseases HIV Infection HIV Infections HIV-associated Hodgkin Lymphoma Hematologic Diseases Hematologic Neoplasms Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Hepatosplenic T-cell Lymphoma Herpesviridae Infections Histiocytic Disorders, Malignant Histiocytosis Hodgkin Disease Immune System Diseases Immunoblastic Lymphadenopathy Immunoglobulin Light-chain Amyloidosis Immunologic Deficiency Syndromes Immunoproliferative Disorders Infections Intraocular Lymphoma Isolated Plasmacytoma of Bone Juvenile Myelomonocytic Leukemia Lentivirus Infections Leukemia Leukemia, B-Cell Leukemia, Biphenotypic, Acute Leukemia, Large Granular Lymphocytic Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Leukemia, Mast-Cell Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid Leukemia, Myeloid, Accelerated Phase Leukemia, Myeloid, Acute Leukemia, Myeloid, Chronic-Phase Leukemia, Myelomonocytic, Chronic Leukemia, Myelomonocytic, Juvenile Leukemia, Neutrophilic, Chronic Leukemia, Prolymphocytic Leukemia, T-Cell Lymphadenopathy Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, B-Cell, Marginal Zone Lymphoma, Extranodal NK-T-Cell Lymphoma, Follicular Lymphoma, Large B-Cell, Diffuse Lymphoma, Large-Cell, Anaplastic Lymphoma, Large-Cell, Immunoblastic Lymphoma, Mantle-Cell Lymphoma, Non-Hodgkin Lymphoma, T-Cell Lymphoma, T-Cell, Cutaneous Lymphoma, T-Cell, Peripheral Lymphoproliferative Disorders Mast Cell Activation Disorders Mast Cell Leukemia Mastocytosis Mastocytosis, Systemic Meningeal Chronic Myelogenous Leukemia Metabolic Diseases Multiple Myeloma Mycosis Fungoides Myelodysplastic-Myeloproliferative Diseases Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Myeloid/NK-cell Acute Leukemia Myeloproliferative Disorders Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Plasma Cell Neoplastic Processes 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 Nutritional and Metabolic Diseases Paraproteinemias Pathologic Processes Pathological Conditions, Signs and Symptoms Pdgfra-Associated Chronic Eosinophilic Leukemia Peripheral T-cell Lymphoma Polycythemia Vera Post-transplant Lymphoproliferative Disorder Precursor Cell Lymphoblastic Leukemia-Lymphoma Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Previously Treated Myelodysplastic Syndromes Primary Central Nervous System Lymphoma Primary Myelofibrosis Primary Systemic Amyloidosis Progressive Hairy Cell Leukemia, Initial Treatment Prolymphocytic Leukemia Proteostasis Deficiencies RNA Virus Infections Retroviridae Infections Secondary Acute Myeloid Leukemia Secondary Myelodysplastic Syndromes Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Sezary Syndrome 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 Thrombocythemia, Essential Thrombocytosis Tumor Virus Infections Unspecified Adult Solid Tumor, Protocol Specific Unspecified Childhood Solid Tumor, Protocol Specific Urogenital Diseases Vascular Diseases Virus Diseases Waldenstrom Macroglobulinemia Waldenström Macroglobulinemia

Age range

Up to 75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

fludarabine phosphate

Drug

Given IV

Other names: 2-F-ara-AMP, Beneflur, Fludara

total-body irradiation

Radiation

Undergo TBI

Other names: TBI

peripheral blood stem cell transplantation

Procedure

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

cyclosporine

Drug

Given IV or PO

Other names: ciclosporin, cyclosporin, cyclosporin A, CYSP, Sandimmune

Mycophenolate mofetil

Drug

Given IV or PO

Other names: Cellcept, MMF

laboratory biomarker analysis

Other

Correlative studies

Primary outcomes

  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 outcomes

  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

Sponsors and collaborators

Lead sponsor

Fred Hutchinson Cancer Center

Other

Collaborators

  • National Cancer Institute (NCI)

Registry information

Official study 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

Important dates

Study start
1999
Primary completion
2014
First posted
Jun 3, 2005
Registry last updated
May 24, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.