A PhaseⅠb Study Evaluating Safety and Efficacy of C-CAR011 Treatment in B- NHL Subjects
Study Details
Study Description
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).
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Detailed Description
The study will include the following sequential phases: Screening, Pre- Treatment (Cell Product Preparation; Lymphodepleting Chemotherapy), Treatment and Follow-up
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: CD19-directed CAR-T cells Lymphocytes will be transduced with lentiviral vector containing CAR-CD19 gene |
Biological: 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
Other Names:
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Outcome Measures
Primary Outcome Measures
- AE [12 weeks]
Incidence of adverse events (AEs) and serious adverse events (SAEs)
Secondary Outcome Measures
- Overall response rate (ORR) [12 months]
The ORR will be assessed at weeks 4 ,weeks 12 ,months 6 and months 12
- Duration of remission (DOR) [12 months]
The DOR will be assessed at months 12
- Progression free survival (PFS) [12 months]
The PFS will be assessed at months 12
- Overall survival rate(OSR) [12 months]
The OSR will be assessed at weeks 12 ,months 6 and months 12
Eligibility Criteria
Criteria
Inclusion Criteria:
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Volunteered to participate in this study and signed informed consent.
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Age 18-70 years old, male or female.
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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)
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DLBCL and Follicular Lymphoma (stage Ⅲ-Ⅳ, grade Ⅲb).
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Progressive disease after the last standard chemotherapy regimens.
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Stable disease after the last standard chemotherapy regimens(at least 4 cycles of first-line therapy or 2 cycles of later-line therapy).
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Relapse or progressive disease within 12 months after autologous stem cell transplantation (SCT).
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Follicular lymphoma (stage Ⅲ-Ⅳ) (gradeⅠ-Ⅲa)
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Relapse or progressive disease within 1 year after the last standard chemotherapy regimens(At least 2 combination chemotherapy regimens).
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Stable disease after the last standard chemotherapy regimens(at least 2 cycles of combination chemotherapy regimens).
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Mantle cell lymphoma
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Relapse after 1st CR or persistent disease, and not eligible or appropriate for SCT.
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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).
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Relapse or progressive disease within 12 months after autologous SCT.
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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).
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At least one measurable lesion per revised IWG Response Criteria (the longest diameter of the tumor ≥ 1.5cm).
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Expected survival ≥ 12 weeks.
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ECOG score 0-1.
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Left ventricular ejection fraction (LVEF) ≥ 50% (detected by echocardiography).
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No active pulmonary infections, normal pulmonary function and oxygen saturation ≥ 92% on room air.
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At least 2 weeks from receiving previous treatment (radiotherapy or chemotherapy) prior to leukapheresis.
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No contraindications of leukapheresis.
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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:
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History of allergy to cellular products.
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Laboratory tests: absolute neutrophil count < 1.0 × 109 /L, platelet count < 50×109 /L, serum albumin < 30 g/L,serum bilirubin > 1.5 ULN, serum creatinine > ULN, ALT/AST
3 ULN.
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History of CAR T cell therapy or any other genetically modified T cell therapy.
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Relapse after allogeneic hematopoietic stem cell transplantation.
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Active infections that require treatment (uncomplicated urinary tract infections and bacterial pharyngitis are allowed), prophylactic antibiotic, antiviral and antifungal treatment are permitted.
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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.
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Class III or IV heart failure according to the NYHA Heart Failure Classifications.
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QT interval prolongation ≥ 450 ms.
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History of epilepsy or other central nervous system disorders.
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Evidence of CNS lymphoma by head enhancement scan or magnetic resonance imaging.
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History of other primary cancers, with the following exceptions.
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Excisional non-melanoma (e.g. cutaneous basal cell carcinoma).
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Cured in situ carcinoma (e.g. cervical cancer, bladder cancer, breast cancer).
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Autoimmune diseases that require treatment, immune deficiency diseases or other diseases that require immunosuppressive therapy.
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Used of systemic steroids within two weeks (using inhaled steroids is an exception).
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Women who are pregnant or lactating, or who have breeding intent in 6 months.
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Participated in any other clinical trial within three months.
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Any situation that investigators believe the risk of the subjects is increased or results of the trial are disturbed.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Peking Union Medical College Hospital | Beijing | Beijing | China | 100010 |
Sponsors and Collaborators
- Peking Union Medical College Hospital
- Cellular Biomedicine Group Ltd.
Investigators
- Principal Investigator: Daobin Zhou, Peking Union Medical College Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CBMG-C2017007