Anti-CD19 U-CAR-T Cell Therapy for B Cell Hematologic Malignancies

• Status: Not yet recruiting
• Trial end date: 2022-04-01
• Target enrollment: 0
• Participant gender: All

Summary

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, based on open clinical trials, using patients' T cells might encounter the failure of apheresis available T cells, even if successful, the time needed for the manufacture could also cause the irreversible disease progress. Furthermore, the cost of auto-CAR-T cells is not affordable for most patients. So to provide an accessible and affordable anti-CD19 CAR-T cell therapy for patients with B-cell hematologic malignancies, we launch such a trial that using the edited T cells from healthy donors to manufacture universal CAR-T cells and adapt it in patients with CD19+ B-cell leukemia or lymphoma.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Xinqiao Hospital of Chongqing
• Collaborators: 920th Hospital of Joint Logistics Support Force; 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China; Central South University; Fujian Medical University Union Hospital; Gracell Biotechnologies (Shanghai) Co., Ltd; Gracell Biotechnology Shanghai Co., Ltd.; Nanfang Hospital of Southern Medical University; Second Affiliated Hospital of Xi'an Jiaotong University; Tang-Du Hospital; The Affiliated Hospital Of Guizhou Medical University; The First Affiliated Hospital of Anhui Medical University; The First Affiliated Hospital of Kunming Medical College; The General Hospital of Western Theater Command; The Second Affiliated Hospital of Chongqing Medical University
• Treatments: Cyclophosphamide; Fludarabine; Fludarabine phosphate; Melphalan

Criteria

Inclusion Criteria:

• 1. Diagnosis of recurrent B-cell acute lymphoblastic leukemia (B-ALL), B-cell acute lymphoblastic lymphoma (B-LLy), or B-non-Hodgkin lymphoma (B-NHL)

2. CD19-positive tumor (≥20% CD19 positive blasts by flow cytometry or immunohistochemistry (tissue)）

3. Hgb ≥ 7.0 (can be transfused)

4. Life expectancy greater than 12 weeks

5. 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. Pregnant or lactating.

2. Tumor in a location where enlargement could cause airway obstruction (per investigator discretion).

3. Active infection with HIV or HTLV.

4. Clinically significant viral infection or uncontrolled viral reactivation of EBV(Epstein-Barr virus), CMV(cytomegalovirus), ADV(adenovirus), BK-virus, or HHV(human herpesvirus)-6.

5. Any of the following cardiac criteria: Atrial fibrillation/flutter; Myocardial infarction within the last 12 months; Prolonged QT syndrome or secondary prolonged QT, per investigator discretion. Cardiac echocardiography with LVSF (left ventricular shortening fraction)<30% or LVEF(left ventricular ejection fraction)<50%; or clinically significant pericardial effusion. Cardiac dysfunction NYHA(New York Heart Association) III or IV (Confirmation of absence of these conditions on echocardiogram within 12 months of treatment).

6. CNS abnormalities: Presence of CNS(central nervous system)-3 disease defined as detectable cerebrospinal blast cells in a sample of CSF(cerebrospinal fluid) with ≥ 5 WBC( white blood cell)s per mm3 (unless negative by the Steinherz/Bleyer algorithm); Presence of any CNS disorder such as an uncontrolled seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.