A Study Evaluating Safety and Efficacy of C-CAR011 in Subjects With B-NHL

NCT ID: NCT03299738

Last Updated: 2017-12-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-31
• Study Completion Date: 2019-08-31

Brief Summary

This is a single arm, single-center, non-randomized study to evaluate the safety and efficacy of C-CAR011 in relapsed or refractory B cell Non-Hodgkin Lymphoma (NHL).

Detailed Description

The study will include the following sequential phases: Screening, Pre-Treatment (Cell Product Preparation, Lymphodepleting Chemotherapy), Treatment and Follow-up.

Conditions

Refractory or Relapsed B-cell Non-Hodgkin Lymphoma

Study Design

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

Study Groups

C-CAR011

Lymphocytes will be transduced with lentiviral vector containing CAR-CD19 gene

Group Type: EXPERIMENTAL

C-CAR011

Intervention Type: BIOLOGICAL

Autologous 2nd generation CD19-directed CAR-T cells, single infusion intravenously at a target dose of 0.5-5.0 x 10\^6 anti-CD19 CAR+ T cells/kg

Interventions

C-CAR011

Autologous 2nd generation CD19-directed CAR-T cells, single infusion intravenously at a target dose of 0.5-5.0 x 10\^6 anti-CD19 CAR+ T cells/kg

Intervention Type: BIOLOGICAL

Other Intervention Names

Anti-CD19 Chimeric Antigen Receptor T cell

Eligibility Criteria

Inclusion Criteria

1. Volunteered to participate in this study and signed informed consent

2. Age 18-70 years old, male or female

3. Relapse or refractory B cell non-Hodgkin's lymphoma

• 1. Histologically diagnosed as DLBCL (including PMBCL) or follicular lymphoma (grade Ⅲb) according to the NCCN non-Hodgkin's lymphoma Clinical Practice Guidelines (2017 Version 1)

• Progressive disease after the last standard chemotherapy regimens per the IWG Response Criteria (1999)
• Stable disease after the last standard chemotherapy regimens (at least 4 cycles of first-line therapy or 2 cycles of later-line therapy) per the IWG Response Criteria (1999)
• Relapse or progressive disease within 12 months after autologous stem cell transplantation (SCT)
• 2. Follicular lymphoma (stage Ⅲ-Ⅳ) (gradeⅠ-Ⅲa)

• At least 2 combination chemotherapy regimens (excluding single agent monoclonal antibody)
• Relapse or progressive disease within 1 year after last chemotherapy regimens
• 3. Mantle cell lymphoma

• Relapse after 1st CR or persistent disease, and not eligible or appropriate for SCT
• Relapse or progressive disease within 1 year after the last chemotherapy regimens
• Relapse or progressive disease within 12 months after autologous SCT

4. All subjects must have received anti-CD20 monoclonal antibody (unless tumor is CD20-negative) and anthracycline-containing chemotherapy regimens according to NCCN non-Hodgkin lymphoma Clinical Practice Guidelines (2017 Version 1)

5. At least one measurable lesion per revised IWG Response Criteria (the longest diameter of the tumor ≥ 1.5 cm)

6. Expected survival ≥ 12 weeks

7. ECOG score 0-1

8. Left ventricular ejection fraction (LVEF) ≥ 50% (detected by echocardiography)

9. No active pulmonary infections, normal pulmonary function and oxygen saturation ≥ 92% on room air

10. At least 2 weeks from receiving previous treatment (radiotherapy or chemotherapy) prior to leukapheresis, or at least 4 weeks from monoclonal antibody therapy prior to CAR T cell therapy

11. No contraindications of leukapheresis

12. Female subjects in childbearing age, their serum or urine pregnancy test must be negative, and must agree to take effective contraceptive measures during the trial

Exclusion Criteria

1. History of allergy to cellular products

2. Laboratory tests: absolute neutrophil count < 1.0 × 10^9 /L, platelet count < 50 × 10^9 /L, serum albumin < 30 g/L, serum bilirubin > 1.5 ULN, serum creatinine > ULN, ALT/AST > 3 ULN

3. History of CAR T cell therapy or any other genetically modified T cell therapy

4. Relapse after allogeneic hematopoietic stem cell transplantation

5. Active infections that require treatment (uncomplicated urinary tract infections and bacterial pharyngitis are allowed), prophylactic antibiotic, antiviral and antifungal treatment are permitted

6. Hepatitis B or hepatitis C virus infection (including carriers), syphilis, as well as acquired or congenital immune deficiency diseases, including but not limited to HIV infection

7. Class III or IV heart failure according to the NYHA Heart Failure Classifications

8. QT interval prolongation ≥ 450 ms

9. History of epilepsy or other central nervous system disorders

10. Evidence of CNS lymphoma by head enhancement scan or magnetic resonance imaging

11. History of other primary cancers, with the following exceptions

• Excisional non-melanoma (e.g. cutaneous basal cell carcinoma)
• Cured in situ carcinoma (e.g. cervical cancer, bladder cancer, breast cancer)

12. Autoimmune diseases that require treatment, immune deficiency diseases or other diseases that require immunosuppressive therapy

13. Used of systemic steroids within two weeks (using inhaled steroids is an exception)

14. Women who are pregnant or lactating, or who have breeding intent in 6 months

15. Participated in any other clinical trial within three months

16. Any situation that investigators believe the risk of the subjects is increased or results of the trial are disturbed

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

Sponsors

Tianjin Medical University Cancer Institute and Hospital

OTHER

Sponsor Role: collaborator

Shanghai AbelZeta Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Huilai Zhang

Role: PRINCIPAL_INVESTIGATOR

Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital

Locations

Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital

Tianjin, , China

Countries

China

Central Contacts

Huilai Zhang

Role: CONTACT

Phone: +86-022-23340123

Facility Contacts

Huilai Zhang

Role: primary

Other Identifiers

CBMG-C2017006

Identifier Type: -

Identifier Source: org_study_id