Safety and Efficacy Study of KL-7SHRNA Injection Solution in the Treatment of AIDS Patients With Lymphoma

This pilot clinical trial studies gene therapy in treating patients with HIV-1 infecetion combined with lymphoma undergoing 7shRNA lentiviral vector transduced CD34+ hematopoietic stem cell transplant. Giving chemotherapy before a stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. After treatment, CD34+hematopoietic stem cells are mobilized and collected from the patient's peripheral blood. The CD34+stem cells are then isolated and transduced with lenti-7shRNA vector and reinfused to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.

Study Overview

• Status: Recruiting
• Conditions: HIV Infections; Lymphoma
• Intervention / Treatment: Drug: KL-7SHRNA injection solution

Detailed Description

Primary objectives:

1. To determine the safety and feasibility of using lenti-7shRNA transduced hematopoietic stem/progenitor cells in the setting of autologous hematopoietic cell transplantation for treatment of HIV infection combined with lymphoma. The safety of the genetically modified product used in the transplant procedure will be assessed by monitoring each subject for adverse events (procedure related toxicity); absolute neutrophil count (ANC)/platelet engraftment (sustained recovery); and evidence of replication competent vector or vector recombination with the human immunodeficiency virus (HIV) quasi-species present in the patient.
2. To determine the quantity and duration of vector-marked peripheral blood cells and to characterize: the duration and level of gene marking and expression of the anti-HIV shRNA in these transduced cells, and the characterization of the integration sites of vector sequences in circulating cells if there is a clinical syndrome suggestive of a clonal expansion of hematopoietic cells. In addition, the feasibility of the process will be assessed based on the results of the release testing of the transduced cells prior to injection into the patient.
3. To measure the effect of HIV infection on the presence of HIV-resistant blood cells as measured by genetic marking for vector sequences before and after antiviral treatment interruption.

• Study Type: Interventional
• Enrollment (Estimated): 3
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: jinqi huang, PhD; Phone Number: +86-0759-2386971; Email: Jinqi@gdmu.edu.cn

Study Locations

• China
  • Guangdong
    • Zhanjiang, Guangdong, China, 524001
      • Recruiting
      • Affiliated Hospital of Guangdong Medical University
      • Contact: jinqi huang, PhD; Phone Number: +86-0759-2386971; Email: Jinqi@gdmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Body mass index (BMI) 18-25, body weight should be ≥ 40kg;
• Meet the Diagnostic Criteria for AIDS and HIV Infection (WS293-2019), and be diagnosed as HIV seropositive;
• HIV infection combined with lymphoma, in partial remission or relapsed after initial complete remission, failed induction therapy, but responds to salvage therapy;
• Age-adjusted IPI 2-3 points;
• Meet the indications for autologous bone marrow transplantation after clinical evaluation;
• HIV viral load <1000 copies/ml;
• Must have the ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

• Any HIV-related uncontrolled opportunistic infection, including fungal infection, sepsis, active tuberculosis, weightlessness, severe diarrhea, active opportunistic infections in the central nervous system or active hepatitis B, hepatitis C, and other viral infections such as CMV;
• Cardiac insufficiency (LVEF<50%), renal insufficiency (creatinine>2mg/dl), hepatic insufficiency (AST/ALT>3 ULN and/or PT <70% unrelated to lymphoma);
• HAART treatment failure (including at least one NRTI, one NNRTI and two PI) and/or CD4 count < 50/cmm);
• Malignancy other than lymphoma, unless (1) in complete remission and more than 5 years from last treatment, or (2) cervical/anal squamous cell carcinoma in situ or (3) superficial basal cell and squamous cell cancers of the skin;
• Participation of other investigational agents (traditional Chinese medicine is not included) within 3 months；
• Any concurrent or past medical condition that, in the opinion of the Investigator, would exclude the subject from participation or any psychosocial conditions that would hinder study compliance or follow-up, at the discretion of the Investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 7shRNA modified CD34+stem cells; Patients undergo high-dose chemotherapy or chemoradiotherapy according to institutional guidelines and then received hematopoietic stem cell transplant on day 0	Drug: KL-7SHRNA injection solution; Patients continue to receive HAART throughout treatment until meet the criteria of interruption of HAART.; Other Names: Drug: carmustine Given IV Other Names: BCNU BiCNU bis-chloronitrosourea; Drug: etoposide Given IV Other Names: EPEG VP-16 VP-16-213; Drug: cytosine arabinoside Given IV; Drug: melphalan Given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Number of patients alive all over the trial	D0 post-infusion to completion of follow-up, an average of 2 year
Engraftment time of 7shRNA modified CD34+ stem cells	Haematological engraftment is defined as first day of neutrophil count >500/mm3 and platelets >20,000/mm3 on 7 consecutive blood counts.	within day +28 after gene therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
7shRNA VCN	Detection of 7shRNA VCN in CD4+T cells via qPRC.	At week 2, months 1, 2, 3, 4, 5, 6, 7, 8, 9，10,12，15,18,21and 24 post-transplant
Duration of interruption of HAART	At two months post-transplant, or later, HAART will be voluntarily interrupted only for participants who have a CD4 count of 200 or higher with no detectable viral load and 7shRNA VCN>0.5, for participants in which the CD4 T-cell count has not risen to ≥ 200 cells/mm3 at the time of the planned HAART interruption, HAART will continue until the T-cell count has risen to ≥ 200 cells/mm3.	Up to 24 months post-treatment
Transplantation related mortality	Number of patients die of transplantation all over the trial	Up to 24 months post-treatment

Collaborators and Investigators

• Sponsor: Affiliated Hospital of Guangdong Medical University
• Investigators: Principal Investigator: yuming Zhang, PhD, Affiliated hospital of Guangdong medical university, Guangdong province, China

Study record dates

Study Major Dates

• Study Start (Estimated): July 5, 2023
• Primary Completion (Estimated): September 10, 2025
• Study Completion (Estimated): April 10, 2026

Study Registration Dates

• First Submitted: June 16, 2023
• First Submitted That Met QC Criteria: June 24, 2023
• First Posted (Actual): June 28, 2023

Study Record Updates

• Last Update Posted (Actual): June 28, 2023
• Last Update Submitted That Met QC Criteria: June 24, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: HIV-1 infection; Lymphoma; gene therapy; 7shRNA
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Etoposide; Melphalan; Carmustine
• Other Study ID Numbers: KL210515

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No