C-CAR066 in Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma (r/r B-NHL)
Study Details
Study Description
Brief Summary
The goal of this multicenter study is to test C-CAR066 in Relapsed or Refractory Non-Hodgkin
Lymphoma Patients. The main questions the study aims to answer are:
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is C-CAR066 safe and do patients tolerate it well?
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what is the best dose of C-CAR066?
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will C-CAR066 help patients achieve a response and for how long?
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
This is a Phase Ib multicenter, open-label study of C-CAR066, an autologous anti-CD20 Chimeric Antigen Receptor (CAR) T cell therapy, for the treatment of adult patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL).
This trial will employ the Bayesian optimal interval (BOIN) design, with a dosing finding Run-In, to find the MTD and/or determine the recommended Phase 2 dose (RP2D).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: C-CAR066
|
Drug: C-CAR066
C-CAR066, an autologous CAR-T therapy targeting CD20
|
Outcome Measures
Primary Outcome Measures
- Calculate the incidence of adverse events [up to 24 months]
The safety and tolerability will be measured by recording the incidence and severity of all adverse events or dose limiting toxicities that occur according to Common Terminology Criteria for Adverse Events (CTCAE) criteria V5.0
- Determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 dose (RP2D) [up to 24 months]
Employ a Bayesian optimal interval (BOIN) design, with a dosing finding Run-In, to find the MTD and/or determine the RP2D with review of the number of dose-limiting toxicities
Secondary Outcome Measures
- Determine the overall response rate (ORR) [up to 24 months]
Record the number of subjects who have a complete response (CR) or partial response (PR) by radiographical assessment using Lugano Criteria 2014
- Determine the time to response (TTR) [up to 24 months]
Record the number of days from the date of C-CAR066 infusion to a CR or PR
- Determine the duration of response (DOR) [up to 24 months]
Record the number of days from the date of the first CR or PR to relapse or death.
- Measure the amount of C-CAR066 in blood over time [up to 24 months]
Review pharmacokinetics (PK) of C-CAR066 by measuring the CAR copy number over time by Quantitative polymerase chain reaction (qPCR).
Other Outcome Measures
- Evaluate progression-free survival [up to 24 months]
Progression-free survival is defined as time from the date of C-CAR066 infusion to the date of first documented disease progression or death, whichever occurs first
- Evaluate overall survival [up to 24 months]
Measure overall survival by days as time from the date of C-CAR066 infusion to the date of death
- Investigate the pharmacodynamic biomarkers [up to 24 months]
Measure serum and whole blood samples to determine cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) and concentration of CD20 positive B cells
- Evaluate the concentration pf anti-drug antibodies (ADA) [up to 24 months]
Determine immunogenicity by measuring the number of anti-drug antibodies in blood over time after administration of C-CAR066
- Measure blood samples to determine concentration of cytokines over time. [up to 24 months]
- Measure blood samples to determine the concentration of CD20 positive B cells over time. [up to 24 months]
Eligibility Criteria
Criteria
Key Inclusion Criteria
Patients will be eligible for the study only if all the following criteria apply:
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Written informed consent must be obtained prior to any screening procedures
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≥ 18 years of age, at the time of signing informed consent
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Diagnosis of aggressive B cell non-Hodgkin lymphoma
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Histologically confirmed CD20 positive disease by immunohistochemistry test result and corresponding pathology report
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Relapsed or refractory disease after ≥ 2 lines of standard therapy (i.e., no response or progression/relapse after first- and second-line therapy) and having relapsed within 12 months of receipt of the most recent anti-lymphoma treatment
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Measurable disease as defined in the IRB approved clinical protocol
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ECOG performance status of either 0 or 1 at screening
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Adequate organ function as defined in the IRB approved clinical protocol
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Life expectancy ≥ 12 weeks
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Women of child-bearing potential (defined as all women physiologically capable of becoming pregnant) and all male participants must agree to use highly effective methods of contraception for one year following C-CAR066 CAR-T therapy
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Sexually active males who accept to use a condom during intercourse drug for 12 months after treatment. A condom is also required by vasectomized men (as well as during intercourse with a male partner) to prevent delivery of the drug via seminal fluid
Key Exclusion Criteria
Patients will be excluded from the study if any of the following criteria apply:
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Human herpes virus (HHV) 8-positive Diffuse large B Cell lymphoma(DLBCL)
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Prior allogeneic Hematopoietic stem cell transplantation (HSCT)
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Autologous stem cell transplant within 12 weeks of CAR T cell infusion
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The exclusion of following medications: Steroids, Immunosuppressive therapy, Chemotherapy, Antibody, Investigational medicinal products and CNS disease prophylaxis
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Received a live vaccine within 4 weeks of leukapheresis
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Uncontrolled active infections as defined in the IRB approved clinical protocol
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History of deep vein thrombosis or pulmonary embolism within six months of infusion (line associated deep vein thrombosis (DVT) is allowed)
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History of stroke, unstable angina, myocardial infarction, congestive heart failure (NYHA Class III or IV), severe cardiomyopathy or ventricular arrhythmia requiring medication or mechanical control within 6 months of screening
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History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease
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Known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system
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Active central nervous system (CNS) involvement by malignancy
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Current active liver or biliary disease (except for Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per Investigator assessment)
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Previous or concurrent malignancy as defined in the IRB approved clinical protocol
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Women of child-bearing potential who are pregnant or breastfeeding
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Severe allergies to fludarabine or cyclophosphamide
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Any known allergies to the components or excipients of the C-CAR066 cell product
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History or current evidence of any condition, therapy, or laboratory abnormality that, in the opinion of the investigator, might confound the results of the trial, interfere with the patient's safe participation and compliance in the trial
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Cellular Biomedicine Group, Inc.
- Mayo Clinic
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CBM-112