HIV-1-infectionNCT03164135
Safety of Transplantation of CRISPR CCR5 Modified CD34+ Cells in HIV-infected Subjects With Hematological Malignances
A study testing CCR5 gene modification in people with HIV-1-infection, run by Affiliated Hospital to Academy of Military Medical Sciences at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- HIV-1-infection
- What is being tested?
- CCR5 gene modification
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteChina
- Study dates
- 30 May 2017to 20 May 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age between 18 to 60, male of female;
- Hematological neoplasms;
- HIV-1 R5 tropic virus with no CXCR4-tropic or R5/X4 dual-tropic HIV;
- On ART with undetectable HIV-1 level (<40gc/ml, HIV-1 RNA);
- Availability of a consenting HLA-matched donor;
- No cardiomyopathy or congestive heart failure;
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- CD4+ T-cell counts ≥200 cells/µL and ≤750 cells/µL;
- Absence of psychosocial conditions and be willing to comply with study-mandated evaluations for 2 years;
- Life expectancy of at least 1 year.
Who cannot join
- Acute or chronic hepatitis B or hepatitis C infection;
- Any cancer or malignancy other than hematological neoplasms;
- Subject with CMV retinitis or other active CMV infection related diseases;
- Subject with organ dysfunction;
- Non-pregnant and non-nursing;
- Drug or alcohol abuse or dependence;
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- Currently enrolled in another clinical trial or underwent cell therapy;
- Donor incapable for HSPC mobilization;
- in the opinion of the site investigator, would interfere with adherence to study requirements.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
307 Hospital of PLA (Affiliated Hospital of Academy to Military Medical Sciences)
Beijing, Beijing Municipality, 100071
Bin Zhang, MD, PhD, +86-10-66947625, zb307ctc@163.com
Lei Xu, MD, PhD, xulei800@hotmail.com
About this study
Official title: Safety and Feasibility Study of Allotransplantation of CRISPR/Cas9 CCR5 Gene Modified CD34+ Hematopoietic Stem/Progenitor Cells in HIV-infected Subjects With Hematological Malignances
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.
Read the 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.
- Conditions
- HIV-1-infection
- Being tested
- CCR5 gene modification
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CCR5 gene modificationGenetic
CD34+ hematopoietic stem/progenitor cells from donor are treated with CRISPR/Cas9 targeting CCR5 gene.
| Study group | Role | What they receive |
|---|---|---|
| CCR5 gene modification | Experimental | CD34+ hematopoietic stem/progenitor cells from donor are treated with CRISPR/Cas9 before transplantation into the patient. Receives: Genetic: CCR5 gene modification |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (1)
CD34+ cell number
The CD34+ cell number pre-infusion
Measured: the first month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2017
- Study start30 May 2017 (estimated)
- Primary completion20 May 2019 (estimated)
- Study completion20 May 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV-1-infectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- CD34+ hematopoietic stem/progenitor cells from donor are treated with CRISPR/Cas9 before transplantation into the patient.
- Masking
- None (open label)
- Enrolment
- 5 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Affiliated Hospital to Academy of Military Medical Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Peking University, Capital Medical University
- Responsible party
- Principal investigator, Chen Hu, Affiliated Hospital to Academy of Military Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03164135
- Sponsor's protocol ID
- 307-HSPC-R5
- Status last verified
- May 2017
- First submitted
- 18 May 2017
- Last updated
- 23 May 2017
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31509667
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Feasibility Study of Allotransplantation of CRISPR/Cas9 CCR5 Gene Modified CD34+ Hematopoietic Stem/Progenitor Cells in HIV-infected Subjects With Hematological Malignances
- ClinicalTrials.gov ID
- NCT03164135
- Acronym / sponsor ID
- 307-HSPC-R5
- Conditions
- HIV-1-infection
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 5 participants (estimated)
- Lead sponsor
- Affiliated Hospital to Academy of Military Medical SciencesUniversity, hospital or other
- Collaborators
- Peking University, Capital Medical University
- Study start
- 30 May 2017 (estimated)
- Primary completion
- 20 May 2019 (estimated)
- Study completion
- 20 May 2021 (estimated)
- First posted
- 23 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- CD34+ hematopoietic stem/progenitor cells from donor are treated with CRISPR/Cas9 before transplantation into the patient.
| Arm | Type | Receives |
|---|---|---|
| CCR5 gene modification | Experimental | Genetic: CCR5 gene modificationCD34+ hematopoietic stem/progenitor cells from donor are treated with CRISPR/Cas9 before transplantation into the patient. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Age between 18 to 60, male of female;
- Hematological neoplasms;
- HIV-1 R5 tropic virus with no CXCR4-tropic or R5/X4 dual-tropic HIV;
- On ART with undetectable HIV-1 level (<40gc/ml, HIV-1 RNA);
- Availability of a consenting HLA-matched donor;
Key exclusion criteria (9 listed)
- Acute or chronic hepatitis B or hepatitis C infection;
- Any cancer or malignancy other than hematological neoplasms;
- Subject with CMV retinitis or other active CMV infection related diseases;
- Subject with organ dysfunction;
- Non-pregnant and non-nursing;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CCR5 gene modificationCD34+ hematopoietic stem/progenitor cells from donor are treated with CRISPR/Cas9 targeting CCR5 gene. | Genetic | CCR5 gene modification |
Primary outcome
Persistence of CCR5 gene disruption in engrafted cells
Time frame: 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.
1 secondary outcome
CD34+ cell number
Time frame: the first month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2017.
- Derived from this study: PubMed 31509667Xu 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CCR5 gene modification in people with HIV-1-infection, run by Affiliated Hospital to Academy of Military Medical Sciences at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Bin Zhang, MD, PhD (+86-10-66947625, zb307ctc@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Persistence of CCR5 gene disruption in engrafted cells (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03164135, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2017.