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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy for individuals with AIDS-related non-Hodgkin lymphoma (NHL) who have previously undergone chemotherapy. The goal is to enhance the body's ability to fight HIV by adding special genes to certain cells, potentially boosting the immune system. Participants receive a chemotherapy drug called busulfan (also known as Busulfex or Myleran) before the gene therapy to improve the effectiveness of the new cells. Suitable candidates have had HIV and NHL, completed initial chemotherapy, and are in remission. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research is exploring a type of gene therapy for treating AIDS-related non-Hodgkin lymphoma (NHL). This therapy uses specially modified cells to strengthen the immune system against AIDS.

Studies have shown that this treatment is generally safe and well-tolerated. Patients did not experience any serious side effects directly linked to the gene therapy. However, like any treatment, side effects could occur, and researchers closely monitor these during trials to minimize and manage any risks effectively.

Gene therapies like this one are still under study, particularly in early trial phases such as Phase 1, which focus mainly on safety. While early results are promising, more research is needed to fully understand the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard chemotherapy treatments for AIDS-related Non-Hodgkin's Lymphoma, which typically target rapidly dividing cancer cells, this gene therapy approach uses a lentivirus vector to deliver modified genes directly into hematopoietic progenitor cells. This method aims to boost the patient's immune system by introducing genes that can potentially block HIV infection and improve immune cell function. Researchers are excited about this treatment because it offers a unique mechanism of action that could provide long-term protection against both the lymphoma and the underlying HIV infection, potentially reducing the need for ongoing chemotherapy and antiretroviral therapy.

What evidence suggests that this gene therapy might be an effective treatment for AIDS-related non-Hodgkin's lymphoma?

Research has shown that a new treatment using modified stem cells might help treat AIDS-related non-Hodgkin lymphoma (NHL). In this trial, participants will receive a gene therapy treatment involving lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells, which are modified to better fight HIV. Lab studies demonstrated that these modified cells resist HIV infection more effectively. The goal is for these cells to aid the immune system in recovering and combating both HIV and lymphoma. Previous trials with similar methods have shown that gene therapies like this could significantly benefit patients with this type of cancer. Although still in early stages, these findings suggest a promising new treatment option. ^{1 2 3 4 5}

Who Is on the Research Team?

Amrita Krishnan

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT00569985

NCT00569985 | Gene Therapy-Treated Stem Cells in ... This pilot clinical trial studies biological therapy in treating patients with acquired immune deficiency syndrome (AIDS)-related lymphoma undergoing stem ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3130552/

RNA-based gene therapy for HIV with lentiviral vector ... CEM cells were transduced with rHIV7-shI-TAR-CCR5RZ as a positive control. Non-transduced CD4+ cells were used as a negative control. 4 μg of total RNA was ...

3. withpower.com withpower.com/trial/phase-1-lymphoma-large-b-cell-diffuse-7-2015-a81b5

Gene Therapy + Chemotherapy for AIDS-Related Lymphoma This pilot clinical trial studies gene therapy following combination chemotherapy in treating patients with acquired immune deficiency syndrome ...

4. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/730576

lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced ... Autologous, CD34-positive hematopoietic progenitor cells (HPCs) transduced with rHIV7-shI-TAR-CCR5RZ, a lentiviral vector encoding three anti-human ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1525001625003089

Clinical hematopoietic stem cell-based gene therapy AIDS-related non-Hodgkin lymphoma, autologous CD34+ cells transduced with rHIV7-shI-TAR-CCR5RZ LV, City of Hope Medical Center, I, 11/20/15 ...