NCT03164135

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
5

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started May 2017

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 18, 2017

Completed
5 days until next milestone

First Posted

Study publicly available on registry

May 23, 2017

Completed
7 days until next milestone

Study Start

First participant enrolled

May 30, 2017

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 20, 2019

Completed
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 20, 2021

Completed
Last Updated

May 23, 2017

Status Verified

May 1, 2017

Enrollment Period

2 years

First QC Date

May 18, 2017

Last Update Submit

May 22, 2017

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (1)

  • CD34+ cell number

    the first month

Other Outcomes (8)

  • Gene disruption efficiency of bone marrow cells

    Up to Month 12

  • CCR5 gene disruption efficiency of peripheral blood cells

    Up to Month 12

  • Hematopoietic cell engraftment

    Up to Year 3

  • +5 more other outcomes

Study Arms (1)

CCR5 gene modification

EXPERIMENTAL

CD34+ hematopoietic stem/progenitor cells from donor are treated with CRISPR/Cas9 before transplantation into the patient.

Genetic: CCR5 gene modification

Interventions

CCR5 gene modificationGENETIC

CD34+ hematopoietic stem/progenitor cells from donor are treated with CRISPR/Cas9 targeting CCR5 gene.

CCR5 gene modification

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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;
  • 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.

You may not qualify if:

  • 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;
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

307 Hospital of PLA (Affiliated Hospital of Academy to Military Medical Sciences)

Beijing, Beijing Municipality, 100071, China

RECRUITING

Related Publications (1)

  • 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.

    PMID: 31509667DERIVED

Central Study Contacts

Bin Zhang, MD, PhD

CONTACT

+86-10-66947625zb307ctc@163.com

Hu Chen, MD, PhD

CONTACT

+86-10-66947108chenhu217@aliyun.com

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: CD34+ hematopoietic stem/progenitor cells from donor are treated with CRISPR/Cas9 before transplantation into the patient.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Study Director

Study Record Dates

First Submitted

May 18, 2017

First Posted

May 23, 2017

Study Start

May 30, 2017

Primary Completion

May 20, 2019

Study Completion

May 20, 2021

Last Updated

May 23, 2017

Record last verified: 2017-05

Data Sharing

IPD Sharing
Will not share

Locations

CN(1)