The Clinical Application of Chimeric Antigen Receptor T Cells in the Treatment of CD19 Positive Recurrent Refractory B Cell-derived Hematological Malignancies

NCT ID: NCT04184414

Last Updated: 2019-12-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-09
• Study Completion Date: 2020-01-01

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.

Conditions

B Acute Lymphoblastic Leukemia; Mantle Cell Lymphoma; Follicular Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CART cells

dosage：Once dose，1.0\*10\^6cells/kg CART cells Administration mode:Intravenous infusion

Group Type: EXPERIMENTAL

CD19-CART

Intervention Type: DRUG

1-10x106 / kg CD19 CART cells

Interventions

CD19-CART

1-10x106 / kg CD19 CART cells

Intervention Type: DRUG

Other Intervention Names

Targeting hcd19 chimeric antigen receptor

Eligibility Criteria

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
• 3. Patients with Burkitt's lymphoma / leukemia (i.e. patients with mature B cell all, B cell surface immunoglobulin positive (SIG +) and light chain kappa or lambda type, morphology Fab L3 or myc ectopic expression)
• 5. Previous use of gene therapy
• 6. Previous use of anti-CD19 / CD3 combination therapy or any other anti-CD19 treatment
• 7. Hepatitis B or C or HBV / HCV or other uncontrolled infection at the time of screening
• 8. Screening with HIV infection
• 9. Acute or chronic graft-versus-host reaction (GVHD) of level 2-4
• 12. Pregnant or lactating women: 48 hours before reinfusion, the female test participants must carry out serum or urine pregnancy test, and the test result is positive
• 13. Women of childbearing age and all men did not take effective contraceptive methods within one year after cart-19 transfusion

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital of Suzhou University

OTHER

Sponsor Role: collaborator

PersonGen BioTherapeutics (Suzhou) Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hematology Department of the Second Affiliated Hospital of Suzhou University

Suzhou, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Bingzong Li, M.D.

Role: CONTACT

lbzwz0907@hotmail.com

+8613776054037

Facility Contacts

Bingzong Li, M.D.

Role: primary

lbzwz0907@hotmail.com

+8613776054037

Other Identifiers

PA-P19-001

Identifier Type: -

Identifier Source: org_study_id