Gene Therapy After Chemotherapy for AIDS-Related Non-Hodgkin's Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must be taking: Prophylactic antibiotics

Must not be taking: Investigational agents

Disqualifiers: Opportunistic infections, Active CMV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

3 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy during the trial.

What data supports the effectiveness of the treatment Gene Therapy After Chemotherapy for AIDS-Related Non-Hodgkin's Lymphoma?

Research shows that gene-modified hematopoietic stem cells can introduce HIV-resistant genes and avoid immune clearance, potentially providing a long-term source of HIV-resistant cells. In trials, patients receiving these gene-modified cells showed improved immune cell counts and some achieved remission from their cancers, suggesting potential effectiveness of this treatment approach. ^{1 2 3 4 5}

Is gene therapy using lentiviral vectors safe for humans?

Research shows that gene therapy using lentiviral vectors in humans has not resulted in serious safety issues, such as the development of replication-competent viruses or cancer, over several years of monitoring. Studies in both mice and humans indicate that these treatments are generally safe, with no significant adverse events reported. ^{1 4 6 7 8}

How is the treatment Lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells different from other treatments for AIDS-related Non-Hodgkin's Lymphoma?

This treatment is unique because it uses gene-modified stem cells to potentially provide a long-term solution by creating HIV-resistant immune cells, unlike traditional treatments that require ongoing medication. It involves transplanting genetically engineered cells that can continuously produce HIV-resistant cells, aiming for a one-time treatment that could offer lasting remission. ^{1 2 3 5 6}

What is the purpose of this trial?

This pilot clinical trial studies gene therapy after frontline chemotherapy in treating patients with acquired immune deficiency syndrome (AIDS)-related non-Hodgkin lymphoma (NHL). Placing genes for anti-human immunodeficiency virus (HIV) ribonucleic acid (RNA) into stem/progenitor cells may make the body build an immune response to AIDS. Giving the chemotherapy drug busulfan before gene therapy can help gene-modified cells engraft and work better.

Research Team

Amrita Krishnan

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for adults with AIDS-related non-Hodgkin lymphoma who've finished frontline chemotherapy. They must have normal liver and kidney function, understand the study, and consent to it. Women of childbearing age need a negative pregnancy test and agree to birth control. Participants can't join if they have uncontrolled illnesses, other cancers, certain infections like active hepatitis or CMV retinitis, or are pregnant.

Inclusion Criteria

I am on, or agree to start, treatment to prevent a specific type of pneumonia due to my low CD4 count.

I am not pregnant and agree to use birth control during and for a year after treatment.

I do not have serious heart disease or heart failure.

Exclusion Criteria

Any AIDS-related opportunistic infection occurring within the past year and for which treatment has been unsuccessful would be considered exclusionary, but this is done on a case-by-case basis as determined by the principal investigator

I do not currently have an active CMV infection affecting my eyes or other organs.

Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study will be considered non-compliant

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Patients receive busulfan intravenously over 3 hours on day -2

1 day

1 visit (in-person)

Gene Therapy Treatment

Lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells are infused intravenously on day 0

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Multiple visits at 1, 7, 14, and 21 days and 1, 2, 3, 6, 9, 12, 18, and 24 months, then annually for 3 years

Treatment Details

Interventions

• Busulfan
• Lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells

Trial Overview The trial tests gene therapy using stem cells modified with anti-HIV RNA after busulfan chemotherapy in patients with AIDS-related NHL. The goal is to see if these modified cells can help the body fight AIDS more effectively.

Participant Groups

Group I: Treatment (gene therapy) Experimental Treatment 4 Interventions

Patients receive busulfan IV over 3 hours on day -2 followed by lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells IV on day 0.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

Findings from Research

In a study involving 375 manufactured T cell products and 308 patients, there was no evidence of replication-competent retrovirus/lentivirus (RCR/L), indicating a strong safety profile for gene-modified cell therapies in HIV and oncology.

The data suggests that patients would need to be monitored for over 52 years to potentially observe an RCR/L event, and the time for lentivirus-modified T cell products to fall below the threshold for vector integration site analysis is relatively short, ranging from 0.66 to 1.4 months depending on the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retroviral and Lentiviral Safety Analysis of Gene-Modified T Cell Products and Infused HIV and Oncology Patients. Marcucci, KT., Jadlowsky, JK., Hwang, WT., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Gene therapy-based treatment for HIV-positive patients with malignancies. [2017]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Stem cell-based therapies for HIV/AIDS. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

RNA-based gene therapy for HIV with lentiviral vector-modified CD34(+) cells in patients undergoing transplantation for AIDS-related lymphoma. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Safety of CD34+ Hematopoietic Stem Cells and CD4+ T Lymphocytes Transduced with LVsh5/C46 in HIV-1 Infected Patients with High-Risk Lymphoma. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Phase I/II Clinical Trials Using Gene-Modified Adult Hematopoietic Stem Cells for HIV: Lessons Learnt. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Hematologic recovery in mice transplanted with bone marrow stem cells expressing anti-human immunodeficiency virus genes. [2012]

7. United States pubmed.ncbi.nlm.nih.gov

In vivo biosafety model to assess the risk of adverse events from retroviral and lentiviral vectors. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Retroviral and Lentiviral Safety Analysis of Gene-Modified T Cell Products and Infused HIV and Oncology Patients. [2019]