Refractory or Relapsed Multiple MyelomaPhase 1/2LEGEND-2NCT03090659
LCAR-B38M Cells in Treating Relapsed/Refractory (R/R) Multiple Myeloma
A Phase 1/2 study testing LCAR-B38M CAR-T cell injection in people with Refractory or Relapsed Multiple Myeloma, run by Nanjing Legend Biotech Co..
Trial summary
This is a single arm, open-label, multi-center, phase 1/2 study, to determine the safety and efficacy of LCAR-B38M CAR-T cells in treating patients diagnosed with refractory/relapsed multiple myeloma (r/r MM). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Refractory or Relapsed Multiple Myeloma
- What is being tested?
- LCAR-B38M CAR-T cell injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- 2 Oct 2015to 31 Dec 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have a confirmed prior diagnosis of active multiple myeloma as defined by the updated IMWG criteria.
- Patients with refractory multiple myeloma. Clear BCMA expression must be detected on malignant plasma cells from either bone marrow or a plasmacytoma by flow cytometry or immunohistochemistry.
- Refractory disease：1) At least 3 prior regimens, which must at least have contained bortezomi. or 2) other circumstances identified by clinical doctors.
- Relapse criteria in NCCN clinical practice guidelines in Oncology: Multiple Myeloma (2016.V2)
Who cannot join
- Women of child-bearing potential or who are pregnant or breastfeeding.
- Have any active and uncontrolled infection: hepatitis B, hepatitis C, HIV, or other fatal viral and bacterial infection.
- Systemic corticosteroid steroid therapy of greater than 5 mg/day of prednisone or equivalent dose of another corticosteroid are not allowed within 2 weeks prior to either the required leukapheresis or the initiation of the conditioning chemotherapy regimen.
- Patients with any uncontrolled intercurrent illness or serious uncontrolled medical disorder.
- Patients with CNS metastases or symptomatic CNS involvement (including cranial neuropathies or mass lesions and spinal cord compression).
- History of allogeneic stem cell transplantation. Have active acute or chronic graft-versus-host-disease (GVHD), or require immunosuppressant medications for GVHD, within 6 months of enrollment.
- Patients with active autoimmune skin diseases such as psoriasis or other active autoimmune diseases such as rheumatoid arthritis.
About this study
Official title: A Clinical Study of Legend Biotech BCMA-chimeric Antigen Receptor Technology in Treating Relapsed/Refractory (R/R) Multiple Myeloma Patients
This is a single arm, open-label, multi-center, phase 1/2 study, to determine the safety and efficacy of LCAR-B38M CAR-T cells in treating patients diagnosed with refractory/relapsed multiple myeloma (r/r MM).
Read the detailed description
Multiple myeloma (MM) is a usually incurable malignancy of plasma cells. Current therapies for multiple myeloma often cause remissions, but nearly all patients eventually relapse and die, an clear unmet clinical needs. As early as mid-2014, the investigators have started to develop a series of proprietary CAR-T products to target B cell maturation antigen (BCMA), a cell surface molecule which the investigator believes to be a desirable target antigen for multiple myeloma. All pre-clinical data and CMC data for LCAR-B38M CAR-T cell technology has been established by mid-2015 and a phase I proof-of-concept clinical trial has been planned since then.
- Conditions
- Refractory or Relapsed Multiple Myeloma
- Being tested
- LCAR-B38M CAR-T cell injection
- Keywords
- multiple myeloma, BCMA, CAR-T
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LCAR-B38M CAR-T cell injectionBiological
| Study group | Role | What they receive |
|---|---|---|
| LCAR-B38M treatment group | Experimental | r/r multiple myeloma patients be treated with a split doses of LCAR-B38M cells. Total dose of 0.5-5 millions /kg cells will be administered at day 0, day 2 and day 6 by split dose (20%, 30% and 50% respectively). Receives: Biological: LCAR-B38M CAR-T cell injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of treatment related adverse events as assessed by CTCAE v4.0
>= Grade 1 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment
Measured: Day 1-30 days after injection
Secondary outcomes (2)
Anti-myeloma responses to LCAR-B38M cell treatment
by measuring the changes of aberrant immunoglobulin in serum
Measured: Day 1-36 months after three split doses
Anti-myeloma responses to LCAR-B38M cell treatment
multiple myeloma cells in bone marrow.
Measured: Day 1-36 months after three split doses
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2017
- Study start2 Oct 2015
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Refractory or Relapsed Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nanjing Legend Biotech Co.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Second Affiliated Hospital of Xi'an Jiaotong University, Ruijin Hospital, Jiangsu Provincial People's Hospital, Shanghai Changzheng Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03090659
- Sponsor's protocol ID
- LCAR-B38M
- Acronym
- LEGEND-2
- Status last verified
- Jun 2023
- First submitted
- 7 Mar 2017
- Last updated
- 12 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Xu J, Wang BY, Yu SH, Chen SJ, Yang SS, Liu R, Chen LJ, Hou J, Chen Z, Zhao WH, He AL, Mi JQ, Chen SJ. Long-term remission and survival in patients with relapsed or refractory multiple myeloma after treatment with LCAR-B38M CAR T cells: 5-year follow-up of the LEGEND-2 trial. J Hematol Oncol. 2024 Apr 24;17(1):23. doi: 10.1186/s13045-024-01530-z.
PubMed 38659046Palmer S, Lin Y, Martin TG, Jagannath S, Jakubowiak A, Usmani SZ, Buyukkaramikli N, Phelps H, Slowik R, Pan F, Valluri S, Pacaud L, Jackson G. Extrapolation of Survival Data Using a Bayesian Approach: A Case Study Leveraging External Data from Cilta-Cel Therapy in Multiple Myeloma. Oncol Ther. 2023 Sep;11(3):313-326. doi: 10.1007/s40487-023-00230-x. Epub 2023 Jun 4.
PubMed 37270762Zhao WH, Wang BY, Chen LJ, Fu WJ, Xu J, Liu J, Jin SW, Chen YX, Cao XM, Yang Y, Zhang YL, Wang FX, Zhang PY, Lei B, Gu LF, Wang JL, Zhang H, Bai J, Xu Y, Zhu H, Du J, Jiang H, Fan XH, Li JY, Hou J, Chen Z, Zhang WG, Mi JQ, Chen SJ, He AL. Four-year follow-up of LCAR-B38M in relapsed or refractory multiple myeloma: a phase 1, single-arm, open-label, multicenter study in China (LEGEND-2). J Hematol Oncol. 2022 Jul 6;15(1):86. doi: 10.1186/s13045-022-01301-8.
PubMed 35794616Zhao WH, Liu J, Wang BY, Chen YX, Cao XM, Yang Y, Zhang YL, Wang FX, Zhang PY, Lei B, Gu LF, Wang JL, Yang N, Zhang R, Zhang H, Shen Y, Bai J, Xu Y, Wang XG, Zhang RL, Wei LL, Li ZF, Li ZZ, Geng Y, He Q, Zhuang QC, Fan XH, He AL, Zhang WG. A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma. J Hematol Oncol. 2018 Dec 20;11(1):141. doi: 10.1186/s13045-018-0681-6.
PubMed 30572922
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Study of Legend Biotech BCMA-chimeric Antigen Receptor Technology in Treating Relapsed/Refractory (R/R) Multiple Myeloma Patients
- ClinicalTrials.gov ID
- NCT03090659
- Acronym / sponsor ID
- LEGEND-2 / LCAR-B38M
- Conditions
- Refractory or Relapsed Multiple Myeloma
- Keywords
- multiple myeloma, BCMA, CAR-T
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Nanjing Legend Biotech Co.Industry (pharma, biotech, devices)
- Collaborators
- Second Affiliated Hospital of Xi'an Jiaotong University, Ruijin Hospital, Jiangsu Provincial People's Hospital, Shanghai Changzheng Hospital
- Study start
- 2 Oct 2015 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 27 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single arm, open-label, multi-center, phase 1/2 study, to determine the safety and efficacy of LCAR-B38M CAR-T cells in treating patients diagnosed with refractory/relapsed multiple myeloma (r/r MM).
Detailed description
Multiple myeloma (MM) is a usually incurable malignancy of plasma cells. Current therapies for multiple myeloma often cause remissions, but nearly all patients eventually relapse and die, an clear unmet clinical needs. As early as mid-2014, the investigators have started to develop a series of proprietary CAR-T products to target B cell maturation antigen (BCMA), a cell surface molecule which the investigator believes to be a desirable target antigen for multiple myeloma. All pre-clinical data and CMC data for LCAR-B38M CAR-T cell technology has been established by mid-2015 and a phase I proof-of-concept clinical trial has been planned since then.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LCAR-B38M treatment group | Experimental | Biological: LCAR-B38M CAR-T cell injectionr/r multiple myeloma patients be treated with a split doses of LCAR-B38M cells. Total dose of 0.5-5 millions /kg cells will be administered at day 0, day 2 and day 6 by split dose (20%, 30% and 50% respectively). |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients must have a confirmed prior diagnosis of active multiple myeloma as defined by the updated IMWG criteria.
- Patients with refractory multiple myeloma. Clear BCMA expression must be detected on malignant plasma cells from either bone marrow or a plasmacytoma by flow cytometry or immunohistochemistry.
- Refractory disease：1) At least 3 prior regimens, which must at least have contained bortezomi. or 2) other circumstances identified by clinical doctors.
- Relapse criteria in NCCN clinical practice guidelines in Oncology: Multiple Myeloma (2016.V2)
Key exclusion criteria (7 listed)
- Women of child-bearing potential or who are pregnant or breastfeeding.
- Have any active and uncontrolled infection: hepatitis B, hepatitis C, HIV, or other fatal viral and bacterial infection.
- Systemic corticosteroid steroid therapy of greater than 5 mg/day of prednisone or equivalent dose of another corticosteroid are not allowed within 2 weeks prior to either the required leukapheresis or the initiation of the conditioning chemotherapy regimen.
- Patients with any uncontrolled intercurrent illness or serious uncontrolled medical disorder.
- Patients with CNS metastases or symptomatic CNS involvement (including cranial neuropathies or mass lesions and spinal cord compression).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LCAR-B38M CAR-T cell injection | Biological | LCAR-B38M treatment group |
Primary outcome
Occurrence of treatment related adverse events as assessed by CTCAE v4.0
Time frame: Day 1-30 days after injection
>= Grade 1 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment
2 secondary outcomes
Anti-myeloma responses to LCAR-B38M cell treatment
Time frame: Day 1-36 months after three split doses
Anti-myeloma responses to LCAR-B38M cell treatment
Time frame: Day 1-36 months after three split doses
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2023.
- Derived from this study: PubMed 38659046Xu J, Wang BY, Yu SH, Chen SJ, Yang SS, Liu R, Chen LJ, Hou J, Chen Z, Zhao WH, He AL, Mi JQ, Chen SJ. Long-term remission and survival in patients with relapsed or refractory multiple myeloma after treatment with LCAR-B38M CAR T cells: 5-year follow-up of the LEGEND-2 trial. J Hematol Oncol. 2024 Apr 24;17(1):23. doi: 10.1186/s13045-024-01530-z.
- Derived from this study: PubMed 37270762Palmer S, Lin Y, Martin TG, Jagannath S, Jakubowiak A, Usmani SZ, Buyukkaramikli N, Phelps H, Slowik R, Pan F, Valluri S, Pacaud L, Jackson G. Extrapolation of Survival Data Using a Bayesian Approach: A Case Study Leveraging External Data from Cilta-Cel Therapy in Multiple Myeloma. Oncol Ther. 2023 Sep;11(3):313-326. doi: 10.1007/s40487-023-00230-x. Epub 2023 Jun 4.
- Derived from this study: PubMed 35794616Zhao WH, Wang BY, Chen LJ, Fu WJ, Xu J, Liu J, Jin SW, Chen YX, Cao XM, Yang Y, Zhang YL, Wang FX, Zhang PY, Lei B, Gu LF, Wang JL, Zhang H, Bai J, Xu Y, Zhu H, Du J, Jiang H, Fan XH, Li JY, Hou J, Chen Z, Zhang WG, Mi JQ, Chen SJ, He AL. Four-year follow-up of LCAR-B38M in relapsed or refractory multiple myeloma: a phase 1, single-arm, open-label, multicenter study in China (LEGEND-2). J Hematol Oncol. 2022 Jul 6;15(1):86. doi: 10.1186/s13045-022-01301-8.
- Derived from this study: PubMed 30572922Zhao WH, Liu J, Wang BY, Chen YX, Cao XM, Yang Y, Zhang YL, Wang FX, Zhang PY, Lei B, Gu LF, Wang JL, Yang N, Zhang R, Zhang H, Shen Y, Bai J, Xu Y, Wang XG, Zhang RL, Wei LL, Li ZF, Li ZZ, Geng Y, He Q, Zhuang QC, Fan XH, He AL, Zhang WG. A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma. J Hematol Oncol. 2018 Dec 20;11(1):141. doi: 10.1186/s13045-018-0681-6.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing LCAR-B38M CAR-T cell injection in people with Refractory or Relapsed Multiple Myeloma, run by Nanjing Legend Biotech Co..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of treatment related adverse events as assessed by CTCAE v4.0 (time frame: Day 1-30 days after injection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03090659, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2023.