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

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ClinicalTrials.gov Identifier: NCT05922384
Recruitment Status : Recruiting
First Posted : June 28, 2023
Last Update Posted : June 28, 2023
Sponsor:
Information provided by (Responsible Party):
Jinqi Huang, Affiliated Hospital of Guangdong Medical University

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
HIV Infections Lymphoma Drug: KL-7SHRNA injection solution Not Applicable

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 3 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Efficacy Study of KL-7SHRNA Injection Solution in the Treatment of AIDS Patients With Lymphoma
Estimated Study Start Date : July 5, 2023
Estimated Primary Completion Date : September 10, 2025
Estimated Study Completion Date : April 10, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV Lymphoma

Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. Overall survival [ Time Frame: D0 post-infusion to completion of follow-up, an average of 2 year ]
    Number of patients alive all over the trial

  2. Engraftment time of 7shRNA modified CD34+ stem cells [ Time Frame: within day +28 after gene therapy ]
    Haematological engraftment is defined as first day of neutrophil count >500/mm3 and platelets >20,000/mm3 on 7 consecutive blood counts.


Secondary Outcome Measures :
  1. 7shRNA VCN [ Time Frame: At week 2, months 1, 2, 3, 4, 5, 6, 7, 8, 9，10,12，15,18,21and 24 post-transplant ]
    Detection of 7shRNA VCN in CD4+T cells via qPRC.

  2. Duration of interruption of HAART [ Time Frame: Up to 24 months post-treatment ]
    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.

  3. Transplantation related mortality [ Time Frame: Up to 24 months post-treatment ]
    Number of patients die of transplantation all over the trial


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05922384


Contacts
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Contact: jinqi huang, PhD +86-0759-2386971 Jinqi@gdmu.edu.cn

Locations
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China, Guangdong
Affiliated hospital of Guangdong medical university Recruiting
Zhanjiang, Guangdong, China, 524001
Contact: jinqi huang, PhD    +86-0759-2386971    Jinqi@gdmu.edu.cn   
Sponsors and Collaborators
Affiliated Hospital of Guangdong Medical University
Investigators
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Principal Investigator: yuming Zhang, PhD Affiliated hospital of Guangdong medical university, Guangdong province, China
More Information
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Responsible Party: Jinqi Huang, Director of Hematology Department, Affiliated Hospital of Guangdong Medical University
ClinicalTrials.gov Identifier: NCT05922384    
Other Study ID Numbers: KL210515
First Posted: June 28, 2023    Key Record Dates
Last Update Posted: June 28, 2023
Last Verified: June 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jinqi Huang, Affiliated Hospital of Guangdong Medical University:
HIV-1 infection; Lymphoma; gene therapy; 7shRNA
Additional relevant MeSH terms:
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Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Etoposide
Melphalan
Carmustine
Antineoplastic Agents, Phytogenic
 Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs