Clinical trial NCT04153279: CMV-TCR-T Cells for CM Virus Infection After HSCT
Official title: A Pilot Study of CMV-TCR-T Cells in CM Virus Infection Diseases After HSCT
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: CMV Infection or Reactivation After Allogenic HSCT
Lead sponsor: Hebei Yanda Ludaopei Hospital
Sponsor class: OTHER
Collaborators: name: China Immunotech (Beijing) Biotechnology Co., Ltd.
First posted: 2019-11-06
Enrollment: 17
Sex: ALL
Minimum age (years): 1
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single cente, single arm, open-label, phase I study to evaluate the safety and effectiveness of CMV-TCR-T cell immunotherapy in treating CMV virus infection after HSCT.

Detailed description: CMV infection is a common virus infection of HSCT, and which is highly related with the failure of transplantation and survival time of transplant patients. To evaluate the safety and efficacy of allogenic CMV-TCR-T cell therapy in subjects with CMV infection, patients with CMV emias or deseases will be enrolled, and donor derived CMV-TCR-T(HLA-A\*1101\\0201\\2402) cells will be intravenously infused with a escalated dose of 0.1-1×106 CMV-TCR-T cells. The CMV DNA copies and CMV-TCR-T cell proliferation will be monitored in the scheduled time (day 0, day 4, day 7, day 10, day 14, day 28).

Eligibility criteria: Inclusion Criteria:

1. Age 1-70 years, including boundary values, gender unlimited;
2. Allogenic hematopoietic stem cell transplantation patients with CMV infection disease or persistent CMV emia;
3. At least one of the following conditions after allogeneic HSCT:

   * After trested with 2-week standard antiviral drug, compared to the baseline of treatment, the decrease of CMV DNA copies number was less than 1log10, and the CMV DNA copies number is greater than 1000 copies/ mL ;
   * Unable to tolerate the toxic and side effects of antiviral drugs,such as bone marrow hematopoietic suppression, nephrotoxicity;
4. Estimated life expectancy ≥3 months；
5. ECOG 3;
6. Patients who voluntarily sign informed consent and are willing to comply with treatment plans, visit arrangements, laboratory tests and other research procedures.

Exclusion Criteria:

1. Patients with active aGVHD III-IV and / or mild and severe cGVHD;
2. Received cell therapy such as DLI,CTL,CAR-T or participated in any other clinical study of drugs and medical devices before 30 days of enrollment.
3. Pregnant or lactating women;
4. Intracranial hypertension or confusion; respiratory failure; disseminated intravascular coagulation;
5. patients with organ failure:

   * Heart: NYHA heart function grade IV;
   * Liver: Grade C that achieves Child-Turcotte liver function grading;
   * Kidney: kidney failure and uremia;
   * Lung: symptoms of respiratory failure;
   * Brain: a person with a disability;
6. The researchers found that it was unsuitable for the recipients to be enrolled.

Primary outcomes:
measure: Percentage of adverse events
timeFrame: 3months
Secondary outcomes:
measure: Persistence of TCR-T cells
timeFrame: 3months
measure: Changes of CMV-DNA copies number
timeFrame: 3months
Other outcomes:
Locations:
city: Sanhe
country: China
facility: Hebei Yanda Ludaopei Hospital
state: Hebei
Study officials:
affiliation: Hebei Yanda Ludaopei Hospital
name: Xingyu Cao, Ph.D
role: STUDY_DIRECTOR
References: