Clinical trial NCT04162353: BCMA-CD19 cCAR in Multiple Myeloma and Plasmacytoid Lymphoma
Official title: BCMA-CD19 cCAR in Relapsed and /or Refractory Multiple Myeloma and Plasmacytoid Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Multiple Myeloma in Relapse
Refractory Multiple Myeloma
Plasmacytoid; Lymphoma
Keywords: BCMA
CD19
BCMA-CD19 cCAR T cells
multiple myeloma
plasmacytoid lymphoma
Lead sponsor: iCell Gene Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: iCAR Bio Therapeutics Ltd.
name: Peking University Shenzhen Hospital
First posted: 2019-11-14
Enrollment: 12
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
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
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of adverse events after BCMA-CD19 cCAR T cells infusion
timeFrame: 2 years particularly the first 28 days after infusion
Secondary outcomes:
measure: Incidence of treatment-emergent adverse events
timeFrame: up to 6 months
Other outcomes:
measure: For multiple myeloma - Stringent complete response
timeFrame: 24 months
measure: For multiple myeloma - Complete response (CR)
timeFrame: 24 months
measure: For multiple myeloma - Very good partial response (VGPR)
timeFrame: 24 months
measure: For multiple myeloma - Partial response (PR)
timeFrame: 24 months
measure: For multiple myeloma - Minimal response (MR)
timeFrame: 24 months
measure: For multiple myeloma - Stable disease (SD)
timeFrame: 24 months
measure: For multiple myeloma - Progressive disease (PD)
timeFrame: 12 months
measure: For multiple myeloma - Progression-free survival (PFS)
timeFrame: up to 24 months
measure: For plasmacytoid lymphoma - Assessment of morphologic CR, CR1, no residual disease, and molecular remission
timeFrame: 1 year
measure: For plasmacytoid lymphoma - Progression-free survival (PFS)
timeFrame: 1 year
measure: For plasmacytoid lymphoma - Overall survival
timeFrame: 1 year
Locations:
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital, China
state: Guangdong
city: Chengdu
country: China
facility: Chengdu Military General Hospital
state: Sichuan
Study officials:
affiliation: Peking University Shenzhen Hospital, China
name: Hongyu Zhang, MD/PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chengdu Military General Hospital
name: Fang Liu, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References: