Anti-CD19 Allo-CAR-T Cells for Relapsed B Cell Malignancies After HSCT

NCT04516551 | Unknown Phase 1

• 1 other identifier: Anti-CD19 allo-CAR-T
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Relapsed Adult ALL; B Cell Leukemia

Outcome Measures

Primary Outcomes (2)

• the safety of anti-CD19 allo CAR-T cells

  Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  within 4 weeks after infusion

• the efficacy of anti-CD19 allo CAR-T cells

  ratio of bone marrow blast cells

  4 weeks after infusion

Secondary Outcomes (1)

• The long-term efficiency

  up to 2 years after infusion

Study Arms (1)

anti-CD19 allo-CAR-T

EXPERIMENTAL

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

Interventions

anti-CD19 allo-CAR-T cells BIOLOGICAL

The T cells collected from haploidentical donors have been manufactured to express CAR to binding CD19 on B-cell leukemia.

anti-CD19 allo-CAR-T

Eligibility Criteria

• Age: 14 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)；
• Severe mental disorders；
• A history of genetic diseases such as Fanconi anemia, Shudder-Dale syndrome, Costman syndrome, or any other known bone marrow failure syndrome；
• Subjects with II-IV grade acute graft versus host disease GVHD (Glucksberg Standrad) or chronic GVHD.
• 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；
• 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)；
• Subjects with a history of CNS lymphoma, CSF malignant cells, or brain metastasis；
• Subjects with a history of CNS disease,such as epilepsy, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving CNS；
• Any of the following virological ELISA results are positive: HIV antibody, HCV antibody, TPPA, HBsAg；
• Active infection requiring systematic treatment within 2 weeks before single collection；
• Subjects with known severe allergic reactions to cyclophosphamide or fludarabine, or diagnosed as the allergy；
• 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；
• Presence of pulmonary fibrosis；
• 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)；
• 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；

Sponsors & Collaborators

• Xinqiao Hospital of Chongqing: lead
• Gracell Biotechnologies (Shanghai) Co., Ltd.: collaborator
• First Affiliated Hospital of Zhejiang University: collaborator
• The Second Affiliated Hospital of Chongqing Medical University: collaborator
• The Affiliated Hospital Of Guizhou Medical University: collaborator
• The General Hospital of Western Theater Command: collaborator
• Chongqing University Cancer Hospital: collaborator
• The First Affiliated Hospital of Anhui Medical University: collaborator
• Tang-Du Hospital: collaborator
• 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China: collaborator

Study Sites (1)

Department of Hematology, Xinqiao Hospital

Chongqing, Chongqing Municipality, 400037, China

RECRUITING

Related Publications (1)

• Luo Y, Gao L, Liu J, Yang L, Wang L, Lai X, Gao S, Liu L, Zhao L, Ye Y, Wang M, Shen L, Cao WW, Wang D, Li W, Zhang X, Huang H. Donor-derived Anti-CD19 CAR T cells GC007g for relapsed or refractory B-cell acute lymphoblastic leukemia after allogeneic HSCT: a phase 1 trial. EClinicalMedicine. 2023 Dec 21;67:102377. doi: 10.1016/j.eclinm.2023.102377. eCollection 2024 Jan.

  PMID: 38204488 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, B-Cell

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Xi Zhang, MD phD

  Xinqiao Hospital of Chongqing

  STUDY CHAIR

• He Huang, MD

  First Affiliated Hospital of Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xi Zhang, MD phD

CONTACT

13808310064; zhangxxi@sina.com

Ruihao Huang

CONTACT

18984398751; 1169731117@qq.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chef of Hematology Department

Study Record Dates

• First Submitted: August 13, 2020
• First Posted: August 18, 2020
• Study Start: November 20, 2020
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2022
• Last Updated: November 17, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)