A Feasibility and Safety Study of Concomitant Therapy With Allo-CAR-T Cells and Allo-HSCT in Patients With Relapse or Refractory Leukemia
Study Details
Study Description
Brief 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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1 |
Detailed Description
-
PRIMARY OBJECTIVES:
-
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.
-
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.
-
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
-
SECONDARY OBJECTIVES:
-
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.
Study Design
Outcome Measures
Primary Outcome Measures
- Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability [24 weeks]
Secondary Outcome Measures
- Overall remission rate (ORR) = CR + CRi [24 weeks]
- Six-month Overall survival [24 weeks]
- Six-month Progression free survival [24 weeks]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female participant
-
12 Years to 60 Years
-
Patient with relapsed or refractory B-cell leukemia or lymphoma
-
Estimated life expectancy ≥ 12 weeks (according to investigator's judgement)
-
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
-
Adequate organ function
Exclusion Criteria:
-
Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease
-
Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic myelogenous leukemia lymphoid blast crisis
-
Richter's syndrome
-
Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening
-
Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy
-
Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis is allowed), Prophylactic antibiotic, antiviral and antifungal treatment is permissible
-
Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening
-
Patient has an investigational medicinal product within the last 30 days prior to screening
-
Previous treatment with investigational gene or cell therapy medicine products
-
Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
-
Pregnant or nursing women
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Biotherapeutic Department and Hematology Department of Chinese PLA General Hospital | Beijing | China | 100853 |
Sponsors and Collaborators
- Chinese PLA General Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CHN-PLAGH-BT-027