Clinical trial NCT04516551: Anti-CD19 Allo-CAR-T Cells for Relapsed B Cell Malignancies After HSCT
Official title: Anti-CD19 Donor-derived CAR-T Cells for Patients With Relapsed B Cell Malignancies After Hematopoietic Stem Cell Transplantation: a Multi-center, Uncontrolled Trial.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Relapsed Adult ALL
B Cell Leukemia
Lead sponsor: Xinqiao Hospital of Chongqing
Sponsor class: OTHER
Collaborators: name: Gracell Biotechnologies (Shanghai) Co., Ltd.
name: First Affiliated Hospital of Zhejiang University
name: The Second Affiliated Hospital of Chongqing Medical University
name: The Affiliated Hospital Of Guizhou Medical University
name: The General Hospital of Western Theater Command
name: Chongqing University Cancer Hospital
name: The First Affiliated Hospital of Anhui Medical University
name: Tang-Du Hospital
name: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
First posted: 2020-08-18
Enrollment: 18
Sex: ALL
Minimum age (years): 14
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of relapsed B-cell acute lymphoblastic leukemia (B-ALL).
2. Patients have received hematologic stem cell transplantation from matching sibling donor or unrelated donor.
3. CD19-positive tumor (\>20% CD19 positive blasts by flow cytometry or immunohistochemistry (tissue)）
4. Hgb ≥ 7.0 (can be transfused)
5. Life expectancy greater than 12 weeks
6. Informed consent explained to, understood by and signed by the patient/guardian. The patient/guardian is given a copy of informed consent.

Exclusion Criteria:

1. 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)；
2. Severe mental disorders；
3. A history of genetic diseases such as Fanconi anemia, Shudder-Dale syndrome, Costman syndrome, or any other known bone marrow failure syndrome；
4. Subjects with II-IV grade acute graft versus host disease GVHD (Glucksberg Standrad) or chronic GVHD.
5. 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；
6. 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)；
7. Subjects with a history of CNS lymphoma, CSF malignant cells, or brain metastasis；
8. Subjects with a history of CNS disease,such as epilepsy, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving CNS；
9. Any of the following virological ELISA results are positive: HIV antibody, HCV antibody, TPPA, HBsAg；
10. Active infection requiring systematic treatment within 2 weeks before single collection；
11. Subjects with known severe allergic reactions to cyclophosphamide or fludarabine, or diagnosed as the allergy；
12. 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；
13. Presence of pulmonary fibrosis；
14. 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)；
15. 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；
16. 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；
17. The lactating woman who is reluctant to stop breastfeeding；
18. Any other condition considered unsuitable by the investigator.

Primary outcomes:
measure: the safety of anti-CD19 allo CAR-T cells
timeFrame: within 4 weeks after infusion
measure: the efficacy of anti-CD19 allo CAR-T cells
timeFrame: 4 weeks after infusion
Secondary outcomes:
measure: The long-term efficiency
timeFrame: up to 2 years after infusion
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Department of Hematology, Xinqiao Hospital
state: Chongqing
Study officials:
affiliation: Xinqiao Hospital of Chongqing
name: Xi Zhang, MD phD
role: STUDY_CHAIR
affiliation: First Affiliated Hospital of Zhejiang University
name: He Huang, MD
role: PRINCIPAL_INVESTIGATOR
References: