B Acute Lymphoblastic Leukemia, Follicular Lymphoma, Mantle Cell Lymphoma
Conditions
Brief summary
CD19 is expressed in most B malignant tumors, especially in the former B cells ALL. This makes CD19 a natural target of immunotherapy. In terms of safety, the lack of B cells caused by CD19 targeted therapy will not cause life-threatening side effects (of course, Ig supplementation is necessary in the long-term B cell inhibition therapy). Moreover, the number of B cells can be restored after removing anti-CD19 treatment measures (such as anti-CD19 CART cells). In addition, CD19 has been chosen as the target of B-ALL therapy for the following reasons: ① as the BCR signal amplifier, CD19 plays a role in PAX-5-mediated tumor formation; ② by activating MYC (as the oncogene controlled by PAX-5, C-MYC plays a key role in promoting the malignant proliferation of B cells), CD19 can cause B-ALL formation. Based on the above reasons, CD19 has become an ideal target in the treatment of B-cell cancer.
Interventions
DRUGCD19-CART
1-10x106 / kg CD19 CART cells
Sponsors
Second Affiliated Hospital of Suzhou University
PersonGen BioTherapeutics (Suzhou) Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* 1\. At the time of initial diagnosis, the age is 18-70 years old, regardless of gender or race * 2\. Morphological analysis showed that the load of lymphoma was ≥ 5% * 3\. Estimated survival time \> 12 weeks * 4\. The main investigator and the attending physician of the patient think that there is no other feasible and effective alternative treatment, such as hematopoietic stem cell transplantation * 5\. Relapsed / refractory B-cell acute lymphocytic leukemia (all): A. objective remission rate (or) of grade 2 or higher bone marrow recurrence B. bone marrow relapse after allogeneic stem cell transplantation (SCT), SCT treatment is more than 6 months and in or state before cart-19 reinfusion C. refractory patients (CR status is not reached after 2 rounds of standard chemotherapy (CR refers to the load of myeloma detected by morphology \< 5%)) D. Philadelphia chromosome positive (Ph +) and tyrosine kinase inhibitor (TKI) treatment failed twice or TKI failed to maintain or E. treatment with allogeneic SCT * 6\. For patients with relapse, CD19 was detected in bone marrow or peripheral blood by flow cytometry within 3 months before admission * 7\. CD19 expression on lymphoma cells: immunohistochemistry \> 15% or flow cytometry \> 30% * 8\. The main organ functions are sound, including: A. renal function: radioisotope glomerular filtration rate \> 60 ml / min / 1.73 m2, or serum creatinine clearance rate in line with relevant age / gender standards B. alanine transferase (ALT) \< 5 times the normal maximum value of the same age C. bilirubin \< 2.0 mg / dl D. to achieve the minimum pulmonary function: ≤ grade I dyspnea and indoor blood oxygen concentration \> 91% E. echocardiography or multi gated angiography (MUGA) showed that the left ventricular short axis shortening rate (LVSF) was ≥ 28%, or left ventricular ejection fraction (LVEF) was ≥ 45% * 9\. Karnofsky score (age ≥ 16 years old) ≥ 50 or zubrod-ecog-who score ≤ 2 * 10\. Sign written informed consent and obtain consent before any research is carried out * 11\. When the above other conditions are met, the cell culture factory must receive fresh blood samples from patients. In the case of monocultured cells, they can only be accepted by the cell culture factory if the relevant tests are qualified
Exclusion criteria
* 1\. Recurrence of isolated extramedullary diseases * 2\. The patient is accompanied by the following genetic syndrome: Fanconi syndrome, Kostmann syndrome, Shwachman syndrome or any known myelofailure syndrome. Patients with Down syndrome are not included in the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CR | 12 weeks after infusion of the study drug | Complete response rate (CR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PR | 12 weeks after infusion of the study drug | Partial remission rate |
| 2-year disease-free survival rate 2-year disease-free survival rate | 12 weeks after infusion of the study drug | 2-year disease-free survival rate |
Countries
China
Contacts
Primary ContactBingzong Li, M.D.
Outcome results
None listed