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.

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

Condition or disease Intervention/treatment Phase
Multiple Myeloma Biological: LCAR-B38M CAR-T Cell Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 28, 2019
Estimated Primary Completion Date : July 20, 2020
Estimated Study Completion Date : April 21, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
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).
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).




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03758417


Contacts
Layout table for location contacts
Contact: Xiaohu Fan 13851733397 frank.fan@legendbiotech.com
Contact: Qiong Wang 18051978283 wangqiong@legendbiotech.com

Locations
Layout table for location information
China, Beijing
Peking University Third Hospital Recruiting
Beijing, Beijing, China, 100191
China, Fujian
Fujian Medical University Union hospital Recruiting
Fuzhou, Fujian, China, 350001
China, Jiangsu
Jiangsu Province Hospital Recruiting
Nanjing, Jiangsu, China, 210029
China, Shanghai
Shanghai Changzheng Hospital Not yet recruiting
Shanghai, Shanghai, China, 200003
Ruijin Hospital, Shanghai Jiao Tong University Recruiting
Shanghai, Shanghai, China, 200025
China, Shanxi
The Second Affiliated Hospital of Xi'an Jiaotong University Recruiting
Xi'an, Shanxi, China, 710004
China, Sichuan
West China Hospital, Sichuan University Recruiting
Chengdu, Sichuan, China, 610041
China, Zhejiang
The First Affiliated Hospital, Medical School of Zhejiang University Recruiting
Hangzhou, Zhejiang, China, 310003
Sponsors and Collaborators
Nanjing Legend Biotech Co.
Janssen Research & Development, LLC
Investigators
Layout table for investigator information
Study Director: Janssen Research&Development,LLC Clinical Trail Janssen Research & Development, LLC

Layout table for additonal information
Responsible Party: Nanjing Legend Biotech Co.
ClinicalTrials.gov Identifier: NCT03758417     History of Changes
Other Study ID Numbers: CR108494
68284528MMY2002 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: November 29, 2018    Key Record Dates
Last Update Posted: May 7, 2019
Last Verified: May 2019

Layout table for additional information
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

Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases