Clinical trial NCT03706547: Anti-CD19/BCMA Bispecific CAR-T Cell Therapy for R/R MM
Official title: Clinical Study of Anti-CD19/BCMA Bispecific Chimeric Antigen Receptors (CARs) T Cell Therapy for Relapsed and Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Multiple Myeloma in Relapse
Multiple Myeloma Progression
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
Collaborators: name: Hrain Biotechnology
name: Shanghai East Hospital
First posted: 2018-10-16
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to study the feasibility and efficacy of anti-CD19/BCMA bispecific chimeric antigen receptors (CARs) T cell therapy for relapsed and refractory multiple myeloma.

Detailed description: Primary Objectives

1. To determine the feasibility ad safety of anti-CD19/BCMA CAR-T cells in treating patients with BCMA-positive multiple myeloma.

Secondary Objectives

1. To access the efficacy of anti-CD19/BCMA CAR-T cells in patients with multiple myeloma.
2. To determine in vivo dynamics and persistency of anti-CD19/BCMA CAR-T cells.

Eligibility criteria: Inclusion Criteria:

* Expected survival \> 12 weeks
* Diagnosis of Multiple Myeloma by IMWG updated criteria (2014)
* Pathology demonstrated that BCMA-poitive malignant plasma cells exited in bone marrow or plamacytoma
* Exited measurable lesions and in accordance with one of the following test indicators: serum M protein≥1 g/dl; urine M protein≥200 mg/24h; serum free light chain≥10 mg/dl; diagnosis of plasmacytoma by biopsy
* The criteria for relapsed and refractory multiple myeloma: patients previously received at least 3 different prior treatment regimens for multiple myeloma, including protein inhibitors (eg: Bortezomib), and immunomodulator (eg: Revlimid), and have disease progression in the past 60 days
* At least 90 days after stem cell transplantation
* Clinical performance status of ECOG score 0-2
* Creatinine≤2.0 mg/dl
* Bilirubin≤2.0 mg/dl
* The ALT/AST value is lower than 2.5-fold of normal value
* Accessible to intravenous injection, and no white blood cell collection contraindications
* Sexually active patients must be willing to utilize one of the more effective birth control methods for 30 days after the CTL infusion. Male partner should use a condom
* 5mg/day dose of Prednisone or other equivalent steroid hormone drugs (eg: Dexamethasone) were not used for two weeks before apheresis and CAR-T infusion
* Able to understand and sign the Informed Consent Document.

Exclusion Criteria:

* Patients with symptoms of central nervous system
* Patients with second malignancies in addition to multiple myeloma
* Active hepatitis B or C, HIV infections
* Any other active diseases could affect the enrollment of this trial
* Long term use of immunosuppressive agents after organ transplantation, except currently receiving or recently received glucocorticoid treatment
* Patients with organ failure
* Women of child-bearing potential who are pregnant or breastfeeding during therapy, or have a planned pregnancy with 2 months after therapy
* A history of mental illness and poorly controlled
* Women of child-bearing potential who are not willing to practice birth control from the time of enrollment on this study and for 2 months after receiving the preparative regimen. Women of child bearing potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion
* Patients who are accounted by researchers to be not appropriate for this test
* Subjects suffering disease affects the understanding of informed consent or complying with study protocol

Primary outcomes:
measure: Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0
timeFrame: 6 months
Secondary outcomes:
measure: Overall remission rate defined by the standard response criteria for myeloma for each arm
timeFrame: 8 weeks
measure: Duration of CAR-positive T cells in circulation
timeFrame: 6 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Department of Hematology ,Fudan University Zhongshan Hospital
Study officials:
affiliation: Shanghai Zhongshan Hospital
name: Peng Liu, M.D. & Ph.D.
role: PRINCIPAL_INVESTIGATOR
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