CD19 Targeted UCAR-T for CD19+ Refractory/Relapsed B-ALL/NHL
Study Details
Study Description
Brief Summary
This is a single arm, open-label, multi-center prospective study to determine the safety and efficacy of CD19 UCAR-T cells in patients diagnosed with CD19+ refractory/relapsed B cell acute lymphoblastic leukemia and B cell non-Hodgkin lymphoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Detailed Description
Who can participate? Patients diagnosed with relapsed/refractory B cell leukaemia or lymphoma.
Before CAR-T infusion, all participants will receive a preconditioning therapy including several chemotherapy agents or other interventions that are required to help the effect of the CAR-T cells. After completion of preconditioning therapy, infusion of the CAR-T cells via a tube into the vein needs to start within 1 week. Participants will receive one infusion of CAR-T cells which will take between 15 and 30 mins. All participants will have a blood test before infusion and at 4, 7, 10 and 14 days following infusion to measure their response to the treatment and some further tests will be required in some participants.
What are the possible benefits and risks of participating? The universal CAR-T cells targeting CD19 may lead to durable disease control and long term survival. The main risks of participating include cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS).
Where is the study run from? Haematology department of 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China (China).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: anti-CD19 UCAR-T treatment Anti-CD19 UCAR-T is an allogeneic CAR-T. A single infusion. |
Biological: anti-CD19 UCAR-T injection
After preconditioning with chemotherapy ( Flu+ Cy), the dosage of anti-CD19 UCAR-T cells between 0.5 and 2 ×10^7 cells/Kg will be evaluated.
|
Outcome Measures
Primary Outcome Measures
- Dose limiting toxicity [Up to 4 weeks after CAR-T infusion]
CRS lasting ≥7 days G3 or ≥G4 after CAR-T infusion
- Incidence of AE after CAR-T infusion [B-ALL up to 12 weeks and B-NHL up to 24 weeks after CAR-T infusion]
Incidence of adverse events after CAR-T infusion
Secondary Outcome Measures
- ORR rate [4 weeks，12 weeks, 24 weeks after CAR-T infusion]
Overall response rate after CAR-T infusion
- PFS [4 weeks，12 weeks, 24 weeks after CAR-T infusion]
Progression free survival after CAR-T infusion
- OS [4 weeks，12 weeks, 24 weeks after CAR-T infusion]
overall survival after CAR-T infusion
- Change of CAR Copies [B-ALL up to 12 weeks and B-NHL up to 24 weeks after CAR-T infusion]
CAR Copies measured by qPCR after CAR-T infusion
- Change of CAR-T cell counts [B-ALL up to 12 weeks and B-NHL up to 24 weeks after CAR-T infusio]
CAR-T cell counts measured by Flow cytometry after CAR-T infusion
- Changes in the concentration of cytokine [Up to 4 weeks after CAR-T infusion]
Cytokines in serum measured by ELISA after CAR-T infusion
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Eastern cooperative oncology group (ECOG) performance status of 0 to 1；
-
Life expectancy ≥12 weeks;
-
Quantifiable tumor burden;
-
Understand and voluntarily sign the informed consent form.
-
Confirmed diagnosis of CD19+ relapsed/refractory B-ALL or B-NHL;
-
Adequate hematological, renal and liver function;
-
Female of childbearing age must agree to take effective contraceptive measures at least 1 year after infusion; Male with fertile partners must agree to use effective barrier contraceptive methods at least 1 year after infusion;
Exclusion Criteria:
-
Diagnosis of other malignancy (except for cured non-melanoma skin cancer, cervical carcinoma in situ, superficial bladder cancer, ductal carcinoma in situ, or other malignancies that have completely responsed for more than 5 years);
-
Severe mental disorders;
-
History of hereditary diseases, including but not limited to: Fanconi anemia, Shut-Dai syndrome, Costman syndrome or any other known bone marrow failure syndrome;
-
History of grade 2-4 acute graft-versus-host disease (GVHD) (Glucksberg criteria) or extensive chronic GVHD (Seattle criteria);
-
Grade III-IV heart failure or myocardial infarction, angioplasty or stent placement, unstableangina pectoris, or other clinically prominent heart disease within one year before enrollment.
-
Subjects with CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases.
-
History or presence of CNS disorder, including but not limited to: seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement;
-
Positive for any of the following etiological tests: HIV, HBV, HCV, TPPA;
-
There were active infections requiring systematic treatment in the 2 weeks prior to screening;
-
Severe Allergic subjects or subjects with allergic reactions to cyclophosphamide or fludarabine;
-
History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years;
-
History or diagnosis of pulmonary fibrosis;
-
Subjects who received other clinical trial therapy within 4 weeks before participating in this trial, or the informed consent form was signed within the 5 half-life of the last administration in the other clinical trial (take longer time as standard);
-
Poor adherence due to physical, family, social, geographic, and other factors, who cannot follow the research plan and follow-up plan;
-
Subjects with comorbidities that require systemic corticosteroid therapy (≥5 mg/day of prednisone or an equivalent dose of other corticosteroids) or other immunosuppressive drugs within 1 months after study therapy according to the discretion of investigator;
-
Donor lymphocyte infusion 6 weeks prior to enrollment;
-
Pregnant women and lactating women who are reluctant to stop breastfeeding;
-
Any other conditions defined by researcher that is inappropriate for the subject to be enrolled;
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China | Kunming | Yunnan | China | 650000 |
Sponsors and Collaborators
- 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
- Gracell Biotechnology Shanghai Co., Ltd.
Investigators
- Principal Investigator: Sanbin Wang, Professor, 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GC502-411