Safety of Transplantation of CRISPR CCR5 Modified CD34+ Cells in HIV-infected Subjects With Hematological Malignances

Not Applicable

• Conditions: HIV-1-infection
• Interventions: Genetic: CCR5 gene modification

• Registration Number: NCT03164135
• Lead Sponsor: Affiliated Hospital to Academy of Military Medical Sciences

Brief Summary

The investigators performed this study to evaluate the safety and feasibility of transplantation with CRISPR/Cas9 CCR5 gene modified CD34+ hematopoietic stem/progenitor cells for patients that develop AIDS and hematological malignances. Patients will be treated with antiviral therapy (ART) to achieve undetectable HIV-1 virus in peripheral blood before conditioning. CD34+ cells from donors will be infused into the patients after treatment with CRISPR/Cas9 to ablate CCR5 gene.

Detailed Description

The primary objective of this study is to determine the safety of the infusion of CD34+ cells which are treated with CRISPR/Cas9 to disrupt the CCR5 gene. The secondary objective is to evaluate the resistance to HIV-1(R5) in infected patients after infusion of modified CD34+ cells with or without an antiretroviral therapy interruption (ATI). After the transplantation, the reconstitution time and frequency of multi-lineage hematopoietic cell will be analyzed against previously reported HSCT in HIV-1 patients. After the detection of high CD4+ T cells reconstitution (over 600 cells/μL) and CCR5 negative cells (over 1%) in peripheral blood, subjects will undergo an ATI. HIV-1 RNA level and CD4+ cell counts will be monitored biweekly for at least one month.

Study Timeline

• Status Verified: 2017-05
• Study First Submitted: 2017-05-18
• Study First Submitted QC: 2017-05-22
• Last Update Submitted: 2017-05-22
• Study First Posted: 2017-05-23
• Last Update Posted: 2017-05-23
• Study Start: 2017-05-30
• Primary Completion: 2019-05-20
• Study Completion: 2021-05-20

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 5

Inclusion Criteria

1. Age between 18 to 60, male of female;
2. Hematological neoplasms;
3. HIV-1 R5 tropic virus with no CXCR4-tropic or R5/X4 dual-tropic HIV;
4. On ART with undetectable HIV-1 level (<40gc/ml, HIV-1 RNA);
5. Availability of a consenting HLA-matched donor;
6. No cardiomyopathy or congestive heart failure;
7. CD4+ T-cell counts ≥200 cells/µL and ≤750 cells/µL;
8. Absence of psychosocial conditions and be willing to comply with study-mandated evaluations for 2 years;
9. Life expectancy of at least 1 year.

Exclusion Criteria

1. Acute or chronic hepatitis B or hepatitis C infection;
2. Any cancer or malignancy other than hematological neoplasms;
3. Subject with CMV retinitis or other active CMV infection related diseases;
4. Subject with organ dysfunction;
5. Non-pregnant and non-nursing;
6. Drug or alcohol abuse or dependence;
7. Currently enrolled in another clinical trial or underwent cell therapy;
8. Donor incapable for HSPC mobilization;
9. in the opinion of the site investigator, would interfere with adherence to study requirements.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CCR5 gene modification	CCR5 gene modification	CD34+ hematopoietic stem/progenitor cells from donor are treated with CRISPR/Cas9 before transplantation into the patient.

Primary Outcome Measures

Name	Time	Method
Persistence of CCR5 gene disruption in engrafted cells	12 months	Participants will be transplanted with CD34+ cells which are treated using the CRISPR/Cas9 system to disrupt CCR5 gene. The persistence of CCR5 gene disruption in engrafted cells will be evaluated by sequencing.

Secondary Outcome Measures

Name	Time	Method
CD34+ cell number	the first month	The CD34+ cell number pre-infusion

Trial Locations

Locations (1)

307 Hospital of PLA (Affiliated Hospital of Academy to Military Medical Sciences); 🇨🇳 Beijing, Beijing, China