A Study of C-CAR039 in Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
Study Details
Study Description
Brief Summary
This is a Phase Ib multicenter, open-label study of C-CAR039, an autologous bi-specific CAR-T therapy targeting CD19 and CD20, for the treatment of adult patients with relapsed or refractory B-Cell non-Hodgkin lymphoma (r/r B-NHL).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: C-CAR039 Autologous C-CAR039 administered by intravenous (IV) infusion |
Biological: CD19/CD20-directed CAR-T cells
Autologous 2nd generation CD19/CD20-directed CAR-T cells, single infusion intravenously
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Incidence of Adverse Events [Safety and Tolerability] [Throughout the first 12 months follow up period completion (3 years)]
Incidence of any adverse events (AEs), including dose limiting toxicities (DLTs)
- The recommended Phase 2 dose (RP2D) of C-CAR039 in patients with r/r B-NHL [Throughout the run-in period completion (an average of 12 months)]
Based on the assessment of dose-limiting toxicities (DLTs) rates and overall safety profile
Secondary Outcome Measures
- Overall response rate (ORR) [Throughout the first 12 months follow up period completion (3 years)]
complete response (CR) rate and partial response (PR) rate
- Time to response (TTR) [Throughout the first 12 months follow up period completion (3 years)]
the time from the date of C-CAR039 infusion to the first documented CR or PR
- Duration of response (DOR) [Throughout the first 12 months follow up period completion (3 years)]
the time from the first documented CR or PR to relapse or death, whichever occurs first
- C-CAR039 CAR copy number by qPCR in peripheral blood [Up to 24 months]
C-CAR039 CAR copy number change over time by qPCR in peripheral blood
- Cmax (maximal plasma concentration) [Up to 24 months]
maximal plasma concentration of C-CAR039 in peripheral blood
- Tmax (Time to reach the maximal plasma concentration) [Up to 24 months]
Time to reach the maximal plasma concentration of C-CAR039 in peripheral blood
- AUCs (area under the curve) [Up to 24 months]
area under the curve of C-CAR039 in peripheral blood
- Presence of replication competent lentivirus (RCL) [Throughout the first 12 months follow up period completion (3 years)]
Measurement of RCL in peripheral blood via a quantitative polymerase chain reaction (qPCR) assay
Other Outcome Measures
- Progression-free survival (PFS) [Throughout the first 12 months follow up period completion (3 years)]
The time from the date of C-CAR039 infusion to the date of first documented disease progression or death
- Overall survival (OS) [Throughout the first 12 months follow up period completion (3 years)]
The time from the date of C-CAR039 infusion to the date of death
- The B cell percentage changes and CD19/CD20 expression changes in blood [up to 24 months]
The B cell percentage changes and CD19/CD20 expression changes in blood by flow cytometry assay before and after C-CAR039 infusion;
- Blood cytokines changes [up to 24 months]
Blood cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) changes over time in blood
- Anti-drug (C-CAR039) antibody [Up to 24 months]
Presence of serum anti-drug (C-CAR039) antibody
Eligibility Criteria
Criteria
Inclusion Criteria
-
≥ 18 years of age, at the time of signing informed consent
-
Diagnosis of aggressive B-cell non-Hodgkin lymphoma, including the following neoplasms as defined by the 2016 WHO classification of lymphoid neoplasms:
-
Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS)
-
Primary mediastinal large B-cell lymphoma (PMBCL)
-
Transformed follicular lymphoma (tFL)
-
High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements
-
High-grade B-cell lymphoma, NOS
-
Follicular lymphoma grade 3B (FL3B)
-
Histologically confirmed CD19 or CD20 positive disease by immunohistochemistry test result and corresponding pathology report
-
Relapsed or refractory disease after ≥ 2 lines of standard therapy and having relapsed within 12 months of receipt of the most recent anti-lymphoma treatment
- For patients with DLBCL, PMBCL, high-grade B-cell lymphomas, tFL and FL grade 3B, patients must have been treated with a line of therapy with an anthracycline and a line of therapy with an anti-CD20 targeted agent
- Measurable disease per the Lugano 2014 Classification, having at least one measurable lesion defined as:
-
Nodal lesion with longest diameter ≥ 1.5 cm
-
Extranodal lesion with longest diameter ≥ 1.0 cm
-
ECOG performance status of either 0 or 1 at screening
-
Adequate bone marrow, liver, renal and cardiopulmonary function
Exclusion Criteria
-
HHV8-positive DLBCL
-
Prior allogeneic HSCT
-
Autologous stem cell transplant within 12 weeks of CAR T cell infusion
-
Inadequate wash-out time for previous anti-tumor treatments prior to C-CAR039 infusion
-
Received a live vaccine within 4 weeks of leukapheresis
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Uncontrolled active HIV, HBC, or HCV infection
-
History of deep vein thrombosis or pulmonary embolism within six months of infusion (line associated DVT is allowed)
-
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
-
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
-
Active 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 (within 5 years) or concurrent malignancy except for basal cell or squamous cell carcinoma or In situ carcinoma of the cervix or breast in complete remission
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Pregnant or lactating women
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Allergies to concomitant drugs used in this study or C-CAR039 cell product
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Other co-morbid condition or disease 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
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | City of Hope Medical Center | Duarte | California | United States | 91010-3000 |
Sponsors and Collaborators
- Cellular Biomedicine Group Ltd.
- City of Hope Medical Center
Investigators
- Principal Investigator: John Baird, M.D., City of Hope Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CCAR039L1101