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| Name | Class |
|---|---|
| Peking University | OTHER |
| Capital Medical University | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CCR5 gene modification | Experimental | CD34+ hematopoietic stem/progenitor cells from donor are treated with CRISPR/Cas9 before transplantation into the patient. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CCR5 gene modification | Genetic | CD34+ hematopoietic stem/progenitor cells from donor are treated with CRISPR/Cas9 targeting CCR5 gene. |
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| Measure | Description | Time Frame |
|---|---|---|
| Persistence of CCR5 gene disruption in engrafted cells | 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. | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| CD34+ cell number | The CD34+ cell number pre-infusion | the first month |
| Measure | Description | Time Frame |
|---|---|---|
| Gene disruption efficiency of bone marrow cells | The percentage of disrupted CCR5 gene alleles in genome from bone marrow cells detected by sequencing. | Up to Month 12 |
| CCR5 gene disruption efficiency of peripheral blood cells |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Bin Zhang, MD, PhD | Contact | +86-10-66947625 | zb307ctc@163.com | |
| Hu Chen, MD, PhD | Contact | +86-10-66947108 | chenhu217@aliyun.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 307 Hospital of PLA (Affiliated Hospital of Academy to Military Medical Sciences) | Recruiting | Beijing | Beijing Municipality | 100071 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31509667 | Derived | Xu L, Wang J, Liu Y, Xie L, Su B, Mou D, Wang L, Liu T, Wang X, Zhang B, Zhao L, Hu L, Ning H, Zhang Y, Deng K, Liu L, Lu X, Zhang T, Xu J, Li C, Wu H, Deng H, Chen H. CRISPR-Edited Stem Cells in a Patient with HIV and Acute Lymphocytic Leukemia. N Engl J Med. 2019 Sep 26;381(13):1240-1247. doi: 10.1056/NEJMoa1817426. Epub 2019 Sep 11. |
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CD34+ hematopoietic stem/progenitor cells from donor are treated with CRISPR/Cas9 before transplantation into the patient.
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The percentage of disrupted CCR5 gene alleles in genome of peripheral blood cells by sequencing.
| Up to Month 12 |
| Hematopoietic cell engraftment | Measurement of multi-lineage hematopoietic cell engraftment time after transplantation to evaluate the hematological recovery | Up to Year 3 |
| HIV-1 RNA level | Level change of HIV-1 RNA in plasma after transplantation | Up to Year 3 |
| CD4+ T cell number | Level change of the CD4+ T cell number after transplantation | Up to Year 3 |
| The ratio change of CD4/CD8 | The ratio change of CD4/CD8 in peripheral blood after transplantation | Up to Year 3 |
| HIV-1 RNA levels during ATI | HIV-1 RNA levels in plasma during ATI. | Every two weeks, until the end of ATI or up to 3 months |
| HIV-1 DNA level | Changes of proviral DNA in PBMC pre- transplantation and 12 month post-transplantation | Up to Month 12 |