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

A Phase 1 Study Evaluating Safety and Efficacy of C-CAR011 in Subjects With B-cell Non-Hodgkin Lymphoma (NHL)

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).

Study Overview

• Status: Unknown
• Conditions: Refractory or Relapsed B-cell Non-Hodgkin Lymphoma
• Intervention / Treatment: Biological: C-CAR011

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Tianjin, China
    • Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: C-CAR011; Lymphocytes will be transduced with lentiviral vector containing CAR-CD19 gene	Biological: 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; Other Names: Anti-CD19 Chimeric Antigen Receptor T cell

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Vital signs, physical examination, clinical laboratory tests, incidence of adverse events (AEs) and serious adverse events (SAEs)	Vital signs, physical examination, clinical laboratory tests, incidence of adverse events (AEs) and serious adverse events (SAEs)	12 weeks
Overall response rate (ORR)		12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression free survival (PFS)	12 months
Overall response rate (ORR)	12 months
Overall survival (OS)	12 months
Overall response rate (ORR)	6 months
Duration of remission (DOR)	12 months

Collaborators and Investigators

• Sponsor: Cellular Biomedicine Group Ltd.
• Collaborators: Tianjin Medical University Cancer Institute and Hospital
• Investigators: Principal Investigator: Huilai Zhang, Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2017
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): August 1, 2019

Study Registration Dates

• First Submitted: September 28, 2017
• First Submitted That Met QC Criteria: October 2, 2017
• First Posted (Actual): October 3, 2017

Study Record Updates

• Last Update Posted (Actual): December 19, 2017
• Last Update Submitted That Met QC Criteria: December 18, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: CBMG-C2017006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No