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

June 24, 2023 updated by: Jinqi Huang, Affiliated Hospital of Guangdong Medical University
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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
3

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Guangdong
      • Zhanjiang, Guangdong, China, 524001
        • Recruiting
        • Affiliated Hospital of Guangdong Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
D0 post-infusion to completion of follow-up, an average of 2 year
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.
within day +28 after gene therapy

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
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
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.
Up to 24 months post-treatment
Transplantation related mortality
Time Frame: Up to 24 months post-treatment
Number of patients die of transplantation all over the trial
Up to 24 months post-treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Affiliated Hospital of Guangdong Medical University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: yuming Zhang, PhD, Affiliated hospital of Guangdong medical university, Guangdong province, China

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 5, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 10, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 10, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 16, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 24, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 28, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 28, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 24, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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