Multiple Myeloma in Relapse, Plasmacytoid; Lymphoma, Refractory Multiple Myeloma
Conditions
Keywords
BCMA, CD19, BCMA-CD19 cCAR T cells, multiple myeloma, plasmacytoid lymphoma
Brief summary
This is a phase I, interventional, single arm, open label, treatment study to evaluate the safety and tolerability of BCMA-CD19 cCAR in patients with relapsed and/or refractory multiple myeloma and plasmacytoid lymphoma.
Detailed description
BCMA-CD19 cCAR is a compound Chimeric Antigen Receptor (cCAR) immunotherapy with two distinct functional CAR molecules expressing on a T-cell, directed against the surface proteins BCMA and CD19. BCMA-CD19 cCAR is also aimed to treat multiple myeloma, a challenging disease due to the heterogeneity of myeloma cells, which renders single-antigen targeting CAR T-cell therapy ineffective. BCMA-CD19 cCAR is proposed to target both bulky myeloma cells expressing BCMA, and myeloma stem cells expressing CD19 to effectively eradicate the disease. BCMA-CD19 cCAR is also aimed to treat heterogeneous plasmacytoid lymphoma bearing two types of lymphoma cells, regular lymphoma cells expressing CD19 and plasmacytoid lymphoma cells expressing BCMA. The use of two different targets intends to increase coverage and eradicate cancerous cells before resistance develops in surviving cancer cells that have undergone selective pressures or antigen escape.
Interventions
BIOLOGICALBCMA-CD19 cCAR T cells
BCMA-CD19 cCAR T cells administered to patients, will be either fresh or thawed CAR T cells by IV injection after receiving lymphodepleting chemotherapy
Sponsors
iCAR Bio Therapeutics Ltd.
Peking University Shenzhen Hospital
iCell Gene Therapeutics
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose escalation phase: BCMA-CD19 cCAR T cells transduced with a lentiviral vector to express two distinct units of BCMA and CD19 CARs on a T cell with an escalation approach, 2e6 to 10e6 CAR-T cells/kg
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Signed written informed consent; Patients volunteer to participate in the research * Diagnosis is mainly based on the World Health Organization (WHO) 2008 * Patients have exhausted standard therapeutic options * Systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 1 weeks * Female must be not pregnant during the study
Exclusion criteria
* Patients declining to consent for treatment * Prior solid organ transplantation * Potentially curative therapy including chemotherapy or hematopoietic cell transplant * Prior treatment with BCMAxCD3 or CD19xCD3 bispecific agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of adverse events after BCMA-CD19 cCAR T cells infusion | 2 years particularly the first 28 days after infusion | Determine the toxicity profile of BCMA-CD19 cCAR T cell therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events | up to 6 months | Incidence of treatment-emergent adverse events |
Other
| Measure | Time frame | Description |
|---|---|---|
| For multiple myeloma - Stable disease (SD) | 24 months | Stable disease (SD) (IMWG criteria) |
| For multiple myeloma - Progressive disease (PD) | 12 months | Progressive disease (PD) (IMWG criteria) |
| For multiple myeloma - Progression-free survival (PFS) | up to 24 months | Progression-free survival (PFS) (IMWG criteria) |
| For plasmacytoid lymphoma - Assessment of morphologic CR, CR1, no residual disease, and molecular remission | 1 year | Assessment of morphologic complete remission (CR), complete remission with incomplete recovery of counts (CR1), no residual disease as analyzed by flow cytometry analysis, and molecular remission by molecular studies |
| For multiple myeloma - Stringent complete response | 24 months | Stringent complete response (sCR) (IMWG criteria) |
| For multiple myeloma - Complete response (CR) | 24 months | Complete response (CR) (IMWG criteria) |
| For multiple myeloma - Very good partial response (VGPR) | 24 months | Very good partial response (VGPR) (IMWG criteria) |
| For multiple myeloma - Partial response (PR) | 24 months | Partial response (PR) (IMWG criteria) |
| For multiple myeloma - Minimal response (MR) | 24 months | Minimal response (MR) (IMWG criteria) |
| For plasmacytoid lymphoma - Overall survival | 1 year | Overall survival |
| For plasmacytoid lymphoma - Progression-free survival (PFS) | 1 year | Progression-free survival (PFS) |
Countries
China
Contacts
Primary ContactKevin Pinz, MS
Outcome results
None listed