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

April 17, 2017 updated by: Ann Woolfrey, Fred Hutchinson Cancer Center

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

5

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 75 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.
Other: laboratory biomarker analysis
Correlative studies
Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Radiation: total-body irradiation
Undergo TBI
Other Names:
  • TBI
Drug: mycophenolate mofetil
Given IV or PO
Other Names:
  • Cellcept
  • MMF
Drug: cyclosporine
Given IV or PO
Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Death From Regimen Toxicity or Opportunistic Infection
Time Frame: Within the first 100 days
Within the first 100 days
Death From GVHD
Time Frame: Within the first 360 days
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
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.
Up to day 80

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: Up to 1 year
Kaplan-Meier estimate assessed at 1 year.
Up to 1 year
Progression of HIV
Time Frame: Within 1 year
Count of participants with HIV progression.
Within 1 year
Reconstitution of HIV-specific Immunity
Time Frame: Up to 1 year
Up to 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fred Hutchinson Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Ann Woolfrey, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 1999

Primary Completion (Actual)

November 1, 2014

Study Registration Dates

First Submitted

June 2, 2005

First Submitted That Met QC Criteria

June 2, 2005

First Posted (Estimate)

June 3, 2005

Study Record Updates

Last Update Posted (Actual)

May 24, 2017

Last Update Submitted That Met QC Criteria

April 17, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 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)
  • NCI-2010-00802 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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