Anti-CD19 Allo-CAR-T Cells for Relapsed B Cell Malignancies After HSCT
Study Details
Study Description
Brief Summary
The patients with relapsed B cell acute lymphoblastic leukemia (ALL) after hematopoietic stem cell transplant (HSCT) have a poor prognosis, especially for these relapsed in a short time after transplantation. Nowadays there is no effective way to salvage patients in such conditions. T cells derived from healthy matched sibling or unrelated donors have not been restrained by tumor micro-environment and retain anti-leukemia ability, which makes it serve well for patients with relapsed B-ALL. So we launched a multi-center clinical trial to proved the safety and efficacy of anti-CD19 CAR-T cells for relapsed B cell ALL.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
The stunning response rate of anti-CD19(cluster of differentiation antigen 19) auto-CAR(chimeric antigen receptor)-T cell therapy brings hope to patients with relapsed or refractory B-cell hematologic malignancies. However, for B-ALL patients suffered from relapse after allo-HSCT (hematopoietic stem cell transplant), the T cells derived from healthy donor seems like a better origin for CAR-T cells producing because T cells derived from healthy matched sibling or unrelated donors have not been restrained by tumor micro-environment and retain anti-leukemia ability. So after we designed a clinical trial to manifest the safety and efficacy of anti-CD19 CAR-T cells for patients with relapsed B cell ALL.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: anti-CD19 allo-CAR-T The study will employ dose level cohorts of three patients that will be treated at each level described below, based on the number of T cells to be infused using the "3 + 3" dose-escalation strategy to find MTD followed by a dose-expansion phase at determining optimal dosage. dosage: the number of anti CD19+CD22 CAR T cells -1(if needed) 1×10^6/KG 3×10^6 /KG 6×10^6 /KG 1×10^7/KG Treatment follows a lymphodepletion, chemotherapy regimen that consists of Fludarabine (30 mg/m2 per day) and Cyclophosphamide (300mg/m2 per day) for 3 days or bendamustione (90mg/m2 per day) for two days prior to cell infusion. |
Biological: anti-CD19 allo-CAR-T cells
The T cells collected from haploidentical donors have been manufactured to express CAR to binding CD19 on B-cell leukemia.
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Outcome Measures
Primary Outcome Measures
- the safety of anti-CD19 allo CAR-T cells [within 4 weeks after infusion]
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
- the efficacy of anti-CD19 allo CAR-T cells [4 weeks after infusion]
ratio of bone marrow blast cells
Secondary Outcome Measures
- The long-term efficiency [up to 2 years after infusion]
ratio of bone marrow blast cells
Eligibility Criteria
Criteria
Inclusion Criteria:
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Diagnosis of relapsed B-cell acute lymphoblastic leukemia (B-ALL).
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Patients have received hematologic stem cell transplantation from matching sibling donor or unrelated donor.
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CD19-positive tumor (>20% CD19 positive blasts by flow cytometry or immunohistochemistry (tissue)）
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Hgb ≥ 7.0 (can be transfused)
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Life expectancy greater than 12 weeks
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Informed consent explained to, understood by and signed by the patient/guardian. The patient/guardian is given a copy of informed consent.
Exclusion Criteria:
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Other tumors except cured non-melanoma skin cancer, cervical cancer in situ, superficial bladder cancer, breast duct cancer in situ, or other malignant tumors with complete remission of more than 5 years)；
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Severe mental disorders；
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A history of genetic diseases such as Fanconi anemia, Shudder-Dale syndrome, Costman syndrome, or any other known bone marrow failure syndrome；
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Subjects with II-IV grade acute graft versus host disease GVHD (Glucksberg Standrad) or chronic GVHD.
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Heart disease with grade III-IV heart failure [NYHA classification], myocardial infarction, angioplasty or stenting, unstable angina or other heart diseases with prominent clinical symptoms within one year before admission；
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Subjects with any indwelling catheter or drainage tube (such as percutaneous nephrostomy tube, bile drainage tube or pleura/peritoneum/pericardium catheter), should be excluded. (Special central venous catheter is allowed)；
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Subjects with a history of CNS lymphoma, CSF malignant cells, or brain metastasis；
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Subjects with a history of CNS disease,such as epilepsy, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving CNS；
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Any of the following virological ELISA results are positive: HIV antibody, HCV antibody, TPPA, HBsAg；
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Active infection requiring systematic treatment within 2 weeks before single collection；
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Subjects with known severe allergic reactions to cyclophosphamide or fludarabine, or diagnosed as the allergy；
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History of autoimmune diseases (e.g. Crohn disease, rheumatoid arthritis, systemic lupus erythematosus) that cause end-organ damage or require systemic immunosuppressive medications or systemic disease modifying drugs in the past 2 years；
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Presence of pulmonary fibrosis；
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Subjects who have received other clinical trial treatment within 4 weeks before participating in this trial should be excluded. Or the signing date of informed consent is within 5 half-lives of the last application of another clinical trial (whichever is longer)；
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Subjects with poor compliance due to physiological, family, social, geographical and other factors, or those unable to cooperate with the study plan or follow-up；
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At the discretion of the investigator, there are complications requiring systemic corticosteroid therapy (≥ 5mg / day of prednisone or equivalent dose of other corticosteroids) or other immunosuppressive drugs within 6 months after this clinical research treatment；
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The lactating woman who is reluctant to stop breastfeeding；
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Any other condition considered unsuitable by the investigator.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Hematology, Xinqiao Hospital | Chongqing | Chongqing | China | 400037 |
Sponsors and Collaborators
- Xinqiao Hospital of Chongqing
- Gracell Biotechnology Shanghai Co., Ltd.
- First Affiliated Hospital of Zhejiang University
- The Second Affiliated Hospital of Chongqing Medical University
- The Affiliated Hospital Of Guizhou Medical University
- The General Hospital of Western Theater Command
- Chongqing University Cancer Hospital
- The First Affiliated Hospital of Anhui Medical University
- Tang-Du Hospital
- 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
Investigators
- Study Chair: Xi Zhang, MD phD, Xinqiao Hospital of Chongqing
- Principal Investigator: He Huang, MD, First Affiliated Hospital of Zhejiang University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Anti-CD19 allo-CAR-T