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

NCT ID: NCT03483688

Last Updated: 2020-03-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-06
• Study Completion Date: 2020-01-10

Brief Summary

This is a single arm, single-center, non-randomized study to evaluate the safety and efficacy of C-CAR011 therapy 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

B-cell Non-Hodgkin Lymphoma

Study Design

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

Study Groups

CD19-directed CAR-T cells

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

Group Type: EXPERIMENTAL

CD19-directed CAR-T cells

Intervention Type: BIOLOGICAL

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

CD19-directed CAR-T cells

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 cells (C- CAR011)

Eligibility Criteria

Inclusion Criteria

• Volunteered to participate in this study and signed informed consent.
• Age 18-70 years old, male or female.
• Relapse or refractory B cell non-Hodgkin's lymphoma ,Histologically diagnosed as DLBCL,follicular lymphoma and Mantle cell lymphoma according to the NCCN. nonHodgkin's lymphoma Clinical Practice Guidelines (2017 Version 1)

1. DLBCL and Follicular Lymphoma (stage Ⅲ-Ⅳ, grade Ⅲb).

1. Progressive disease after the last standard chemotherapy regimens.

2. Stable disease after the last standard chemotherapy regimens(at least 4 cycles of first-line therapy or 2 cycles of later-line therapy).

3. Relapse or progressive disease within 12 months after autologous stem cell transplantation (SCT).

2. Follicular lymphoma (stage Ⅲ-Ⅳ) (gradeⅠ-Ⅲa)

1. Relapse or progressive disease within 1 year after the last standard chemotherapy regimens(At least 2 combination chemotherapy regimens).

2. Stable disease after the last standard chemotherapy regimens(at least 2 cycles of combination chemotherapy regimens).

3. Mantle cell lymphoma

1. Relapse after 1st CR or persistent disease, and not eligible or appropriate for SCT.

2. Relapse or progressive disease within 1 year after the last chemotherapy regimens(at least 4 cycles of first-line therapy or 2 cycles of later- line therapy).

3. Relapse or progressive disease within 12 months after autologous SCT.

• 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).
• At least one measurable lesion per revised IWG Response Criteria (the longest diameter of the tumor ≥ 1.5cm).
• Expected survival ≥ 12 weeks.
• ECOG score 0-1.
• Left ventricular ejection fraction (LVEF) ≥ 50% (detected by echocardiography).
• No active pulmonary infections, normal pulmonary function and oxygen saturation ≥ 92% on room air.
• At least 2 weeks from receiving previous treatment (radiotherapy or chemotherapy) prior to leukapheresis.
• No contraindications of leukapheresis.
• 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

• History of allergy to cellular products.
• 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.
• History of CAR T cell therapy or any other genetically modified T cell therapy.
• Relapse after allogeneic hematopoietic stem cell transplantation.
• Active infections that require treatment (uncomplicated urinary tract infections and bacterial pharyngitis are allowed), prophylactic antibiotic, antiviral and antifungal treatment are permitted.
• 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.
• Class III or IV heart failure according to the NYHA Heart Failure Classifications.
• QT interval prolongation ≥ 450 ms.
• History of epilepsy or other central nervous system disorders.
• Evidence of CNS lymphoma by head enhancement scan or magnetic resonance imaging.
• History of other primary cancers, with the following exceptions.

1. Excisional non-melanoma (e.g. cutaneous basal cell carcinoma).

2. Cured in situ carcinoma (e.g. cervical cancer, bladder cancer, breast cancer).

• Autoimmune diseases that require treatment, immune deficiency diseases or other diseases that require immunosuppressive therapy.
• Used of systemic steroids within two weeks (using inhaled steroids is an exception).
• Women who are pregnant or lactating, or who have breeding intent in 6 months.
• Participated in any other clinical trial within three months.
• 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

Shanghai AbelZeta Ltd.

INDUSTRY

Sponsor Role: collaborator

Peking Union Medical College Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daobin Zhou

Role: PRINCIPAL_INVESTIGATOR

Peking Union Medical College Hospital

Locations

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Countries

China

References

Zhang L, Zhang Y, Zhou DB. [Anti-CD19 CART (C-CAR011) Therapy for Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2021 Aug;29(4):1141-1147. doi: 10.19746/j.cnki.issn.1009-2137.2021.04.019. Chinese.

Reference Type: DERIVED

PMID: 34362494 (View on PubMed)

Other Identifiers

CBMG-C2017007

Identifier Type: -

Identifier Source: org_study_id