Competitive Transfer of αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T Cells for B-cell Leukemia/Lymphoma

• Status: Unknown status
• Trial end date: 2019-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a single-arm open-label phase I/II study to determine the relative superiority of αCD19-TCRζ-CD28 and αCD19-TCRζ-CD137 CAR-T Cells in safety, efficacy and engraftment potential in patients with CD19+ B-lineage leukemia and lymphoma. Recently, cancer immunotherapy, treatments aiming to arm patients with immunity specifically against cancer cells, has emerged as a promising therapeutic strategy. Clinical trials utilizing CARs against B cell malignancies have demonstrated remarkable potential. In this trial, all subjects will be competitively infused with αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T cells in equal number to test a hypothesis that CD137-costimulation can promote the persistence and engraftment of CAR-T cells and this superiority can lead to improved progression-free survival.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine
• Collaborators: Xinqiao Hospital of Chongqing; Xuzhou Medical University
• Treatments: Cyclophosphamide; Fludarabine

Criteria

Inclusion Criteria:

1. 5 Years to 70 Years, Male and female;

2. Expected survival > 12 weeks;

3. Performance score 0-2;

4. Histologically confirmed as CD19-positive lymphoma/leukemia and who meet one of the following conditions;

• Patient receive at least 2-4 prior combination chemotherapy regimens (not including single agent monoclonal antibody therapy) and fail to achieve CR; or have disease recurrence; or not eligible for allogeneic stem cell transplantation; or disease responding or stable after most recent therapy but refused further treatment;

• Disease recurrence after stem cell transplantation;

• Diagnosis as lymphoma, but refuse conventional treatment such as chemotherapy, radiation, stem cell transplantation and monoclonal antibody therapy

5. Creatinine < 2.5 mg/dl;

6. ALT/AST < 3x normal;

7. Bilirubin < 2.0 mg/dl;

8. Adequate venous access for apheresis, and no other contraindications for leukapheresis;

9. Take contraceptive measures before recruit to this trial;

10. Written voluntary informed consent is given.

Exclusion Criteria:

1. Patients with symptoms of central nervous system

2. Accompanied by other malignant tumor

3. Active hepatitis B or C, HIV infection

4. Any other diseases could affect the outcome of this trial

5. Suffering severe cardiovascular or respiratory disease

6. Poorly controlled hypertension

7. A history of mental illness and poorly controlled

8. Taking immunosuppressive agents within 1 week due to organ transplantation or other disease which need long-lasting administration

9. Occurrence of unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events 30 days prior to assignment

10. Reaching a steady dose if receiving anticoagulant therapy before assignment

11. Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion

12. Pregnant or lactating women

13. Subject suffering disease affects the understanding of informed consent or comply with study protocol.