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

Primary Purpose

HIV Infections, Lymphoma

Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
KL-7SHRNA injection solution
Sponsored by
Affiliated Hospital of Guangdong Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring HIV-1 infection; Lymphoma; gene therapy; 7shRNA

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Affiliated hospital of Guangdong medical universityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

7shRNA modified CD34+stem cells

Arm Description

Patients undergo high-dose chemotherapy or chemoradiotherapy according to institutional guidelines and then received hematopoietic stem cell transplant on day 0

Outcomes

Primary Outcome Measures

Overall survival
Number of patients alive all over the trial
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.

Secondary Outcome Measures

7shRNA VCN
Detection of 7shRNA VCN in CD4+T cells via qPRC.
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.
Transplantation related mortality
Number of patients die of transplantation all over the trial

Full Information

First Posted
June 16, 2023
Last Updated
June 24, 2023
Sponsor
Affiliated Hospital of Guangdong Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT05922384
Brief Title
Safety and Efficacy Study of KL-7SHRNA Injection Solution in the Treatment of AIDS Patients With Lymphoma
Official Title
Safety and Efficacy Study of KL-7SHRNA Injection Solution in the Treatment of AIDS Patients With Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 5, 2023 (Anticipated)
Primary Completion Date
September 10, 2025 (Anticipated)
Study Completion Date
April 10, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Affiliated Hospital of Guangdong Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
Primary objectives: 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. 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, Lymphoma
Keywords
HIV-1 infection; Lymphoma; gene therapy; 7shRNA

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
7shRNA modified CD34+stem cells
Arm Type
Experimental
Arm Description
Patients undergo high-dose chemotherapy or chemoradiotherapy according to institutional guidelines and then received hematopoietic stem cell transplant on day 0
Intervention Type
Drug
Intervention Name(s)
KL-7SHRNA injection solution
Other Intervention Name(s)
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
Intervention Description
Patients continue to receive HAART throughout treatment until meet the criteria of interruption of HAART.
Primary Outcome Measure Information:
Title
Overall survival
Description
Number of patients alive all over the trial
Time Frame
D0 post-infusion to completion of follow-up, an average of 2 year
Title
Engraftment time of 7shRNA modified CD34+ stem cells
Description
Haematological engraftment is defined as first day of neutrophil count >500/mm3 and platelets >20,000/mm3 on 7 consecutive blood counts.
Time Frame
within day +28 after gene therapy
Secondary Outcome Measure Information:
Title
7shRNA VCN
Description
Detection of 7shRNA VCN in CD4+T cells via qPRC.
Time Frame
At week 2, months 1, 2, 3, 4, 5, 6, 7, 8, 9,10,12,15,18,21and 24 post-transplant
Title
Duration of interruption of HAART
Description
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.
Time Frame
Up to 24 months post-treatment
Title
Transplantation related mortality
Description
Number of patients die of transplantation all over the trial
Time Frame
Up to 24 months post-treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
jinqi huang, PhD
Phone
+86-0759-2386971
Email
Jinqi@gdmu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
yuming Zhang, PhD
Organizational Affiliation
Affiliated hospital of Guangdong medical university, Guangdong province, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Affiliated hospital of Guangdong medical university
City
Zhanjiang
State/Province
Guangdong
ZIP/Postal Code
524001
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
jinqi huang, PhD
Phone
+86-0759-2386971
Email
Jinqi@gdmu.edu.cn

12. IPD Sharing Statement

Plan to Share IPD
No

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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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