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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03463928
Other study ID # CHN-PLAGH-BT-027
Secondary ID
Status Recruiting
Phase Phase 1
First received March 7, 2018
Last updated March 12, 2018
Start date October 8, 2017
Est. completion date December 2019

Study information

Verified date March 2018
Source Chinese PLA General Hospital
Contact Hejin Jia
Phone 86-10-55499341
Email jiahejin@163.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Allogenic hematopoietic stem cell transplant (Allo-HSCT) is routinely used for treatment of aggressive hematological malignancies. The biological foundation of allo-HSCT is the graft-versus-leukemia (GVL) effect, which is primarily mediated by donor T cells present in the graft and is able to eradicate malignant B cells either CD19+ or CD19-. Relapse following an allo-HSCT remains a major challenge in the treatment of B-ALL. CD19-directed CAR-T cell therapy has shown promising results for the treatment of relapsed or refractory B-cell malignancies; however, a subset of patients relapse due to the loss of CD19 in tumor cells. Co-infusion of donor-derived CD19/22 bispecific CAR-T cells or CD19-directed CAR-T cells and donor-derived-HSCT has the potential to combine the CAR-T cell mediated targeted elimination of CD19 expressing B cells with GVL effect, which could have clear advantages in reducing the risk of relapse and the evolution of CD19− escape variants or clonally related malignancies in other lineages. Therefore, a complete and durable tumor responses induced by this immunotherapy could be expected.


Description:

1. PRIMARY OBJECTIVES:

1. To evaluate the feasibility and safety of donor-derived HSCT following donor-derived CD19/22 bispecific CAR-T cells or CD19-directed CAR-T cells in patients with relapsed or refractory leukemia.

2. To evaluate the duration of in vivo persistence of adoptively transferred CAR-T cells, and the phenotype of persisting T cells. Real Time polymerase chain receptor (RT-PCR) and Flow cytometry(FCM) analysis of PB,BM will be used to detect and quantify survival of infused allo-CAR-T cells over time.

3. To evaluate the donor chimerism after co-infusion of donor-derived CD19/22 bispecific CAR-T cells or CD19-directed CAR-T cells and donor-derived-HSCT

2. SECONDARY OBJECTIVES:

1. For patients with detectable disease, measure anti-tumor response due to co-infusion of donor-derived CD19/22 bispecific CAR-T cells or CD19-directed CAR-T cells and donor-derived-HSCT.

The allo-CAR-T cells will be infused in a fractionated manner, 1/3 on day 0, 2/3 on day 1.The allo-HSCT will be infused on day 2.


Recruitment information / eligibility

Status Recruiting
Enrollment 10
Est. completion date December 2019
Est. primary completion date June 2019
Accepts healthy volunteers No
Gender All
Age group 12 Years to 60 Years
Eligibility Inclusion Criteria:

1. Male or female participant

2. 12 Years to 60 Years

3. Patient with relapsed or refractory B-cell leukemia or lymphoma

4. Estimated life expectancy = 12 weeks (according to investigator's judgement)

5. Eastern Cooperative Oncology Group (ECOG) performance status = 1

6. Adequate organ function

Exclusion Criteria:

1. Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease

2. Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic myelogenous leukemia lymphoid blast crisis

3. Richter's syndrome

4. Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening

5. Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy

6. Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis is allowed), Prophylactic antibiotic, antiviral and antifungal treatment is permissible

7. Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening

8. Patient has an investigational medicinal product within the last 30 days prior to screening

9. Previous treatment with investigational gene or cell therapy medicine products

10. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary

11. Pregnant or nursing women

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
donor-derived CD19/22 bispecific CAR-T cells or CD19-directed CAR-T cells; donor-derived-HSCT
The allo-CAR-T cells will be infused in a fractionated manner, 1/3 on day 0, 2/3 on day 1.The allo-HSCT will be infused on day 2.

Locations

Country Name City State
China Biotherapeutic Department and Hematology Department of Chinese PLA General Hospital Beijing

Sponsors (1)

Lead Sponsor Collaborator
Chinese PLA General Hospital

Country where clinical trial is conducted

China, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability 24 weeks
Secondary Overall remission rate (ORR) = CR + CRi 24 weeks
Secondary Six-month Overall survival 24 weeks
Secondary Six-month Progression free survival 24 weeks
See also
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