B-cell Acute Lymphoblastic Leukemia, B-cell Lymphoma
Conditions
Brief 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.
Interventions
BIOLOGICALanti-CD19 UCAR-T cells
Dose range:1 to 5 ×10\^7 cells/Kg, Dose level one: 1×10\^7 cells/Kg, Dose level two: 3×10\^7 cells/Kg, Dose level three:5 ×10\^7 cells/Kg
DRUGFludarabine
30mg/m\^2 per day for 6 days
DRUGCytoxan
300mg/m\^2 per day for 2 to 6 days determined by tumor burden at baseline
DRUGMelphalan
50 to 70 mg/m\^2 in total for 1 or 2 days, whether to use determined by tumor burden at baseline
Sponsors
Gracell Biotechnologies (Shanghai) Co., Ltd.
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
The Second Affiliated Hospital of Chongqing Medical University
The Affiliated Hospital Of Guizhou Medical University
Central South University
First Affiliated Hospital of Kunming Medical University
The General Hospital of Western Theater Command
Second Affiliated Hospital of Xi'an Jiaotong University
Nanfang Hospital, Southern Medical University
Fujian Medical University Union Hospital
The First Affiliated Hospital of Anhui Medical University
Tang-Du Hospital
Xinqiao Hospital of Chongqing
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the anti-tumor efficiency of anti-CD19 UCAR-T cells | 4 weeks after infusion | ratio of bone marrow blast cells and/or the measurable lesion size and strandralized uptake value |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| the long-term efficiency of anti-CD19 UCAR-T cells | 3 and 6 months after infusion | ratio of bone marrow blast cells and/or the measurable lesion size and strandralized uptake value |
Countries
China
Contacts
Primary ContactXi Zhang, MD
Backup ContactRuihao Huang
Outcome results
None listed