Clinical trial NCT03758417: A Study of LCAR-B38M CAR-T Cells, a Chimeric Antigen Receptor T-cell (CAR-T) Therapy Directed Against B-cell Maturation Antigen (BCMA) in Chinese Participants With Relapsed or Refractory Multiple Myeloma
Official title: A Phase 2, Open-Label Study of LCAR-B38M CAR-T Cells, a Chimeric Antigen Receptor T-cell (CAR-T) Therapy Directed Against BCMA in Chinese Subjects With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Multiple Myeloma
Lead sponsor: Nanjing Legend Biotech Co.
Sponsor class: INDUSTRY
Collaborators: name: Janssen Research & Development, LLC
First posted: 2018-11-29
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of LCAR-B38M chimeric antigen receptor T (CAR-T) cells.


Eligibility criteria: Inclusion Criteria:

* Documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria
* Measurable disease at Screening
* Received at least 3 prior lines of treatment for multiple myeloma

  a) Undergone at least 1 complete cycle of treatment for each line, unless progressive disease (PD) was documented by IMWG criteria as the best response to the regimen
* Received a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD)
* Participant must have documented evidence of progressive disease based on investigator's determination of response consistent with IMWG criteria on or within 12 months of their last regimen. Non-responsive disease is defined as either failure to achieve minimal response or development of progressive disease (PD) while on therapy. Also, participants with documented evidence of PD disease (as above) within the previous 6 months and who are refractory or non-responsive to their most recent line of treatment afterwards are eligible
* Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 or 1

Exclusion Criteria:

* Prior treatment with chimeric antigen receptor T (cells) CAR-T therapy directed at any target
* Any therapy that is targeted to B-cell maturation antigen (BCMA)
* The following cardiac conditions: a) New York Heart Association (NYHA) stage III or IV congestive heart failure b) Myocardial infarction or coronary artery bypass graft (CABG) 6 months prior to enrollment c) History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration d) History of severe non-ischemic cardiomyopathy e) Impaired cardiac function (left ventricular ejection fraction \[LVEF\] less than \[\<\]45%) as assessed by echocardiogram or multiple-gated acquisition (MUGA) scan (performed less than or equal to (\<=) 8 weeks of apheresis)
* Have received a cumulative dose of corticosteroids equivalent to greater than or equal to(\>=)70 milligram (mg) of prednisone within 7 days prior to apheresis
* Diagnosed or treated for invasive malignancy other than multiple myeloma, except:

  1. Malignancy treated with curative intent and with no known active disease present for greater than or equal to (\>=) 2 years before enrollment; or
  2. Adequately treated non-melanoma skin cancer without evidence of disease
* Prior antitumor therapy with insufficient washout period
* Toxicity from previous anticancer therapy must resolve to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy
* Received either of the following:

  1. An allogeneic stem cell transplant for multiple myeloma
  2. An autologous stem cell transplant less than or equal to (\<=) 12 weeks before apheresis
* Known active, or prior history of, central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Minimum 2 years after LCAR-B38M chimeric antigen receptor T (CAR-T) infusion (Day 1)
Secondary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)
measure: Chimeric Antigen Receptor T (CAR-T) Positive Cell Concentration
timeFrame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)
measure: Transgene Levels of LCAR-B38M CAR-T Cells
timeFrame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)
measure: Systemic Cytokine Concentrations
timeFrame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)
measure: Number of Participants With Anti- LCAR-B38M CAR-T Cell Antibodies
timeFrame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)
measure: Percentage of Participants with Very Good Partial Response (VGPR) or Better Rate
timeFrame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)
measure: Percentage of Participants with Complete Response (CR)
timeFrame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)
measure: Percentage of Participants with Negative Minimal Residual Disease (MRD)
timeFrame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)
measure: Percentage of Participants who Achieve Clinical Benefit
timeFrame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)
measure: Duration of Response (DOR)
timeFrame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)
measure: Time to Response (TTR)
timeFrame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)
measure: Progression-Free Survival (PFS)
timeFrame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)
measure: Overall survival (OS)
timeFrame: Mnimum 2 years after LCAR-B38M CART infusion (Day 1)
measure: Levels of CAR-T cell Activation Markers
timeFrame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)
measure: Levels of LCAR-B38M CAR-T cell Expansion (proliferation)
timeFrame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)
measure: Levels of LCAR-B38M CAR-T Persistence
timeFrame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)
measure: Percentage of Participants with Stringent Complete Response (sCR)
timeFrame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)
measure: Circulating Soluble B-Cell Maturation Antigen (sBCMA) Levels
timeFrame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)
measure: Percent Reduction in BCMA Expression Cells
timeFrame: Minimum 2 years after LCAR-B38M CART infusion (Day 1)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Medical University Union hospital
state: Fujian
city: Guandong
country: China
facility: Sun Yat -Sen University Cancer Center
state: Guangzhou
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Shanghai
country: China
facility: Shanghai Changzheng Hospital
state: Shanghai
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiao Tong University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Fourth People Hospital
state: Shanghai
city: Xi'an
country: China
facility: The Second Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Medical School of Zhejiang University
state: Zhejiang
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research&Development,LLC Clinical Trail
role: STUDY_DIRECTOR
References:
citation: Mi JQ, Zhao W, Jing H, Fu W, Hu J, Chen L, Zhang Y, Yao D, Chen D, Schecter JM, Yang F, Tian X, Sun H, Zhuang SH, Ren J, Fan X, Jin J, Niu T, Chen SJ. Phase II, Open-Label Study of Ciltacabtagene Autoleucel, an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor-T-Cell Therapy, in Chinese Patients With Relapsed/Refractory Multiple Myeloma (CARTIFAN-1). J Clin Oncol. 2023 Feb 20;41(6):1275-1284. doi: 10.1200/JCO.22.00690. Epub 2022 Oct 21.