Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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 (CARTIFAN-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03758417
Recruitment Status : Recruiting
First Posted : November 29, 2018
Last Update Posted : May 7, 2019
Sponsor:
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Nanjing Legend Biotech Co.

Tracking Information
First Submitted Date  ICMJE November 27, 2018
First Posted Date  ICMJE November 29, 2018
Last Update Posted Date May 7, 2019
Actual Study Start Date  ICMJE January 28, 2019
Estimated Primary Completion Date July 20, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 27, 2018)
Overall Response Rate (ORR) [ Time Frame: Minimum 2 years after LCAR-B38M chimeric antigen receptor T (CAR-T) infusion (Day 1) ]
The ORR is defined as the percentage of participants who achieve partial response (PR) or better according to international myeloma working group (IMWG) criteria.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03758417 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 19, 2019)
  • Number of Participants With Adverse Events [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
  • Chimeric Antigen Receptor T (CAR-T) Positive Cell Concentration [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Venous blood samples will be collected for measurement of CAR-T positive cellular concentration.
  • Transgene Levels of LCAR-B38M CAR-T Cells [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Transgene Levels of LCAR-B38M CAR-T Cells using sensitive assay methods will be assessed.
  • Systemic Cytokine Concentrations [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Serum cytokine concentrations such as Interleukin [IL]-6, IL-15, IL-10 will be measured for biomarker assessment.
  • Number of Participants With Anti- LCAR-B38M CAR-T Cell Antibodies [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Number of participants with anti- LCAR-B38M CAR-T cell antibodies will be evaluated.
  • Percentage of Participants with Very Good Partial Response (VGPR) or Better Rate [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    The VGPR or better rate, defined as the percentage of participants achieving VGPR and complete response (CR) (including stringent complete response [sCR]) according to IMWG criteria during or after the study treatment. IMWG criteria for VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or greater than or equal to (>=) 90 percent (%) reduction in serum Mprotein plus urine M-protein less than (<) 100 milligram (mg)/24 hours, CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells (PCs) in bone marrow. sCR: CR plus normal free light chain (FLC) ratio, and absence of clonal PCs by immunohistochemistry (IHC), immunofluorescence for 2 to 4 color flow cytometry.
  • Percentage of Participants with Complete Response (CR) [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Complete response is based on serum M-Protein and bone marrow assessments as per IMWG criteria.
  • Percentage of Participants with Negative Minimal Residual Disease (MRD) [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Minimal residual disease negative rate is defined as the percentage of participants who achieve MRD negative status by the respective time point. MRD will be assessed by bone marrow 8-colored flow cytometry.
  • Percentage of Participants who Achieve Clinical Benefit [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Clinical Benefit Rate is defined as the percentage of participants who achieve ORR (sCR + CR + VGPR + PR) and minimal response (MR) as per IMWG criteria.
  • Duration of Response (DOR) [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Duration of response (DOR) will be calculated among responders (with a PR or better response) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria.
  • Time to Response (TTR) [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Time to response (TTR) is defined as the time between date of the initial infusion of LCAR-B38M CAR-T cells and the first efficacy evaluation that the participant has met all criteria for PR or better.
  • Progression-Free Survival (PFS) [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    PFS defined as time from date of initial infusion of LCAR-B38M CAR-T cells to date of first documented disease progression, defined in the IMWG criteria, or death due to any cause, whichever occurs first.
  • Overall survival (OS) [ Time Frame: Mnimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Overall survival (OS) is measured from the date of infusion of the LCAR-B38M CAR-T cells to the date of the participant's death.
  • Levels of CAR-T cell Activation Markers [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Levels of CAR-T cell Activation Markers like CD4+, CD8+, and CD25+ will be assessed. An evaluation of cell populations may be performed by flow cytometry.
  • Levels of LCAR-B38M CAR-T cell Expansion (proliferation) [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Levels of LCAR-B38M CAR-T cell expansion (proliferation) will be reported.
  • Levels of LCAR-B38M CAR-T Persistence [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Levels of LCAR-B38M CAR-T persistence will be evaluated via monitoring CAR-T positive cell counts and CART transgene levels.
  • Percentage of Participants with Stringent Complete Response (sCR) [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Stringent Complete Response (sCR) is based on serum M-Protein and bone marrow assessments as per IMWG criteria for complete response(CR) plus normal free light chain (FLC) ratio, and absence of clonal PCs by immunohistochemistry(IHC), or 2 to 4 color flow cytometry.
  • Circulating Soluble B-Cell Maturation Antigen (sBCMA) Levels [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Blood samples will be collected for measurement of sBCMA level.
  • Percent Reduction in BCMA Expression Cells [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Percent reduction in BCMA Expression Cells will be measured.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 27, 2018)
  • Number of Participants With Adverse Events [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
  • Chimeric Antigen Receptor T (CAR-T) Positive Cell Concentration [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Venous blood samples will be collected for measurement of CAR-T positive cellular concentration.
  • Transgene Levels of LCAR-B38M CAR-T Cells [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Transgene Levels of LCAR-B38M CAR-T Cells using sensitive assay methods will be assessed.
  • Systemic Cytokine Concentrations [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Serum cytokine concentrations such as Interleukin [IL]-6, IL-15, IL-10 will be measured for biomarker assessment.
  • Immune Related Proteins Levels [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Immune related proteins (such as perforin and granzymes) levels will be assessed.
  • Number of Participants With Anti- LCAR-B38M CAR-T Cell Antibodies [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Number of participants with anti- LCAR-B38M CAR-T cell antibodies will be evaluated.
  • Percentage of Participants with Very Good Partial Response (VGPR) or Better Rate [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    The VGPR or better rate, defined as the percentage of participants achieving VGPR and complete response (CR) (including stringent complete response [sCR]) according to IMWG criteria during or after the study treatment. IMWG criteria for VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or greater than or equal to (>=) 90 percent (%) reduction in serum Mprotein plus urine M-protein less than (<) 100 milligram (mg)/24 hours, CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells (PCs) in bone marrow. sCR: CR plus normal free light chain (FLC) ratio, and absence of clonal PCs by immunohistochemistry (IHC), immunofluorescence for 2 to 4 color flow cytometry.
  • Percentage of Participants with Complete Response (CR) [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Complete response is based on serum MProtein assessments as per IMWG criteria.
  • Percentage of Participants with Negative Minimal Residual Disease (MRD) [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Minimal residual disease negative rate is defined as the percentage of participants who achieve MRD negative status by the respective time point. MRD will be assessed by bone marrow 8-colored flow cytometry.
  • Percentage of Participants who Achieve Clinical Benefit [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Clinical Benefit Rate is defined as the percentage of participants who achieve ORR (sCR + CR + VGPR + PR) and minimal response (MR) as per IMWG criteria.
  • Duration of Response (DOR) [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Duration of response (DOR) will be calculated among responders (with a PR or better response) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria.
  • Time to Response (TTR) [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Time to response (TTR) is defined as the time between date of the initial infusion of LCAR-B38M CAR-T cells and the first efficacy evaluation that the participant has met all criteria for PR or better.
  • Progression-Free Survival (PFS) [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    PFS defined as time from date of initial infusion of LCAR-B38M CAR-T cells to date of first documented disease progression, defined in the IMWG criteria, or death due to any cause, whichever occurs first.
  • Overall survival (OS) [ Time Frame: Mnimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Overall survival (OS) is measured from the date of infusion of the LCAR-B38M CAR-T cells to the date of the participant's death.
  • Levels of CAR-T cell Activation Markers [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Levels of CAR-T cell Activation Markers like CD4+, CD8+ will be assessed. An evaluation of cell populations may be performed by flow cytometry.
  • Levels of LCAR-B38M CAR-T cell Expansion (proliferation) [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Levels of LCAR-B38M CAR-T cell expansion (proliferation) will be reported.
  • Levels of LCAR-B38M CAR-T Persistence [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Levels of LCAR-B38M CAR-T persistence will be reported.
  • Stringent Complete Response (sCR) [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Stringent Complete response is based on serum M-Protein assessments as per IMWG criteria.
  • Circulating Soluble B-Cell Maturation Antigen (sBCMA) Levels [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Blood samples will be collected for measurement of sBCMA level.
  • Percent Reduction in BCMA Expression Cells [ Time Frame: Minimum 2 years after LCAR-B38M CART infusion (Day 1) ]
    Percent reduction in BCMA Expression Cells will be measured.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
Brief Summary The purpose of this study is to evaluate the efficacy and safety of LCAR-B38M chimeric antigen receptor T (CAR-T) cells.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE Biological: LCAR-B38M CAR-T Cell
Participants will receive LCAR-B38M CAR-T cells as a single infusion which consists of autologous T lymphocytes transduced with LCAR-B38M, a lentiviral vector to express a chimeric antigen receptor targeting the human B cell maturation antigen (anti-BCMA CAR).
Study Arms  ICMJE Experimental: LCAR-B38M Chimeric Antigen Receptor T Cell
Participants will receive LCAR-B38M CAR-T cells as a single infusion which consists of autologous T lymphocytes transduced with LCAR-B38M, a lentiviral vector to express a chimeric antigen receptor targeting the human B cell maturation antigen (anti-BCMA CAR).
Intervention: Biological: LCAR-B38M CAR-T Cell
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 27, 2018)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 21, 2022
Estimated Primary Completion Date July 20, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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 (>=) 3 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Xiaohu Fan 13851733397 frank.fan@legendbiotech.com
Contact: Qiong Wang 18051978283 wangqiong@legendbiotech.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03758417
Other Study ID Numbers  ICMJE CR108494
68284528MMY2002 ( Other Identifier: Janssen Research & Development, LLC )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Nanjing Legend Biotech Co.
Study Sponsor  ICMJE Nanjing Legend Biotech Co.
Collaborators  ICMJE Janssen Research & Development, LLC
Investigators  ICMJE
Study Director: Janssen Research&Development,LLC Clinical Trail Janssen Research & Development, LLC
PRS Account Nanjing Legend Biotech Co.
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP