Clinical trial NCT03093168: BCMA Chimeric Antigen Receptor Expressing T Cells in Multiple Myeloma
Official title: A Phase I Clinical Trial of T-Cells Targeting B-Cell Maturation Antigen for Subjects With BCMA-positive Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Multiple Myeloma
Lead sponsor: The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine
Sponsor class: OTHER
Collaborators: name: Hrain Biotechnology Co., Ltd.
name: First Affiliated Hospital of Wenzhou Medical University
name: Shanghai Changzheng Hospital
First posted: 2017-03-28
Enrollment: 10
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-B-Cell Maturation Antigen (BCMA) expressing T cells in treating patients with multiple myeloma.

Detailed description: Primary Objectives

1. To determine the feasibility ad safety of BCMA CAR-T cells in treating patients with multiple myeloma.
2. To determine in vivo dynamics and persistency of BCMA CAR-T cells.
3. To access the efficacy of BCMA CAR-T cells in patients with multiple myeloma.

Secondary Objectives

1. To assess the bone marrow and tumor migration of BCMA CAR-T cells.
2. To investigate the tumor killing capability of BCMA CAR-T cells in vitro
3. To investigate the possibility of host immune response to the mouse derived BCMA scFv, and evaluate its correlation to CAR-T persistence.
4. To correlate the subsets and differentiation of BCMA CAR-T cells to observed anti-tumor efficacy.

Eligibility criteria: Inclusion Criteria:

* Expected survival \> 12 weeks
* Diagnosis of Multiple Myeloma by MWG criteria 20
* Patients previously received at least 3 different prior treatment regimens for multiple myeloma, including alkylating agent, protein inhibitors, and immunomodulator, and have disease progression in the past 60 days
* Important organs function enough to tolerate this therapy
* At least 90 days after stem cell transplantation
* Clinical performance status of ECOG score 0-4
* 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
* 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
* Suffering severe cardiovascular or respiratory disease
* Poorly controlled hypertension
* Long term use of immunosuppressive agents after organ transplantation, except currently receiving or recently received glucocorticoid treatment
* A history of mental illness and poorly controlled
* Screening showing target cell transduction efficacy is lower than 30%, or T cell proliferation is not enough for infusion (less than 5 fold)
* Occurrence of unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events 30 days prior to assignment
* Women of child-bearing potential who are pregnant or breastfeeding during therapy, or have a planned pregnancy with 2 months after therapy
* 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
* Active systemic infections or uncontrolled infection within 14 days prior enrollment
* 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 complete remission rate defined by the standard response criteria for malignant lymphoma for each arm
timeFrame: 8 weeks
measure: Duration of CAR-positive T cells in circulation
timeFrame: 6 months
measure: Total number of CAR-positive T cells infiltrated into lymphoma tissue
timeFrame: 6 months
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: Henan Province of TCM
state: Henan
Study officials:
References: