Gene Therapy in HIV-Positive Patients With Non-Hodgkin's Lymphoma

This study has been completed.
Sponsor:
Information provided by:
NIH AIDS Clinical Trials Information Service
ClinicalTrials.gov Identifier:
NCT00002221
First received: November 2, 1999
Last updated: June 23, 2005
Last verified: June 2003
  Purpose

The purpose of this study is to see if it is safe and effective to use gene therapy to treat non-Hodgkin's lymphoma (NHL) in HIV-positive patients.

Stem cell transplantation is a procedure used to treat NHL. Stem cells are very immature cells that develop to create all of the different types of blood cells. In this study, some of your stem cells will be treated with gene therapy, meaning the cells are treated with a virus that does not cause disease. Some cells will receive a virus that contains ribozymes, enzymes that may help fight HIV. Other cells will be treated with a virus that does not contain ribozymes to see how the virus works alone. Some cells will not be treated at all. Doctors would like to see whether giving patients stem cells with ribozymes can treat NHL and stop HIV from growing at the same time.


Condition Intervention Phase
Lymphoma, Non-Hodgkin
HIV Infections
Drug: Peripheral blood stem cells
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Primary Purpose: Treatment
Official Title: High Dose Chemotherapy and Autologous Peripheral Stem Cell Transplantation for HIV Lymphomas: A Phase IIA Study of Comparative Marking Using a Ribozyme Gene and a Neutral Gene

Resource links provided by NLM:


Further study details as provided by NIH AIDS Clinical Trials Information Service:

Estimated Enrollment: 5
Detailed Description:

In this study, CD34+ cells (stem cells) are transduced with a retroviral vector construct that incorporates multiple ribozymes, a form of RNA with the ability to selectively inhibit gene expression, targeting different sites within the HIV virus. These transduced cells are reinfused into patients as part of a bone marrow transplant procedure for AIDS/lymphoma.

Patients undergoing autologous bone marrow transplantation are entered into this study. A "neutral" retrovirus named "LN" and a retrovirus that contains two ribozyme sequences named "L-TR/Tat-neo" are introduced into the patient's PBPC. The L-TR/Tat-neo retrovirus has been shown in tissue culture experiments to inhibit the replication of HIV. The LN retrovirus serves as an internal control to examine selective advantage of the gene therapy. Patients have a bone marrow sample taken. After an additional round of chemotherapy with their referring physician, patients receive daily injections of G-CSF to aid in the collection of stem cells. Daily stem cell collections are performed. It is anticipated that three to four collections will be required, but as many as six may be necessary. To prepare for the transplantation of stem cells, patients are admitted for a 7-day series of intensive chemotherapy. Following this conditioning, the gene-modified and untreated stem cells are infused back into the patient. The collected cells are divided into three pools. One is set aside without modification, one is modified with the LN control vector, and one is modified with the L-TR/Tat-neo construct. The LN and L-TR/Tat-neo samples are pooled and given to the patient by IV infusion over about 15 minutes. The unmodified cells are then infused over 10 to 15 minutes. Patients remain in the hospital until their blood cells return to adequate levels and they are well enough to be released. Following transplantation, all patients are followed at Months 1, 3, 6, 9, 12, 18, and 24. Because of the experimental nature of gene therapy, patients are followed periodically throughout their lifetimes.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

You may be eligible for this study if you:

  • Are 18 to 60 years old.
  • Have been HIV-positive at least since you were diagnosed with non-Hodgkin's lymphoma.
  • Have an HIV level less than or equal to 25,000 copies/ml and a CD4 count of at least 100 cells/mm3.
  • Are currently about to undergo bone marrow transplantation.
  • Have responded well to cancer treatments, including chemotherapy and previous bone marrow transplantation.
  • Agree to use effective barrier methods of birth control, such as condoms, during the study.
  • Are on anti-HIV therapy (HAART).

Exclusion Criteria

You will not be eligible for this study if you:

  • Have lymphoma affecting your nervous system.
  • Have had any AIDS-related opportunistic infections in the past year.
  • Have heart disease.
  • Are pregnant or breast-feeding.
  • Have severe diarrhea.
  • Have a history of cytomegalovirus (CMV) retinitis.
  • Have dementia or encephalopathy (an infection of the brain).
  • Have a history of another type of cancer (except for skin cancer) before your diagnosis of NHL.
  • Are allergic to etoposide or have had a toxic reaction to prior chemotherapy.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002221

Locations
United States, California
City of Hope Natl Med Ctr
Duarte, California, United States, 91010
Sponsors and Collaborators
Ribozyome
Investigators
Study Chair: John Zaia
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00002221     History of Changes
Other Study ID Numbers: STUDY 2
Study First Received: November 2, 1999
Last Updated: June 23, 2005
Health Authority: United States: Food and Drug Administration

Keywords provided by NIH AIDS Clinical Trials Information Service:
Lymphoma, Non-Hodgkin
Bone Marrow
Lymphocyte Transformation
HIV-1
Retroviridae
Lymphoma, AIDS-Related
Genetic Vectors
Transduction, Genetic
Gene Transfer Techniques

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lymphoma
Lymphoma, Non-Hodgkin
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders

ClinicalTrials.gov processed this record on August 20, 2014