Multiple Myeloma, RefractoryPhase 1LMY-920-002NCT05546723
LMY-920 for Treatment of Relapsed or Refractory Myeloma
A Phase 1 study testing Autologous CAR-T cell therapy expressing the BAFF-ligand. in people with Multiple Myeloma, Refractory and Multiple Myeloma in Relapse, run by Luminary Therapeutics at 1 site in United States.
Trial summary
Since CAR-T cell treatment of refractory myeloma has shown success, based on preclinical data, we posit that CAR-T cells expressing B-cell activating factor (BAFF) can become another strategy to treat refractory myeloma, even after relapse following BCMA targeting CAR-T cell treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma, Refractory, Multiple Myeloma in Relapse
- What is being tested?
- Autologous CAR-T cell therapy expressing the BAFF-ligand.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Mar 2024to 31 Oct 2025
- Phase
- Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must have histologically confirmed myeloma relapsed or refractory after 3 or more lines of therapy including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody. Failing line of therapy is defined accordingly to International Myeloma Workshop Consensus Panel.
- No evidence of CNS myeloma.
- Male or female > 18 years of age.
- ECOG Performance status ≤ 2.
- Has measurable disease at the time of enrollment as defined by at least one of the following:
- Serum M-protein greater or equal to 0.5g/dL
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- Urine M-protein greater or equal to 200mg/24hr
- Serum free light chain (FLC) assay: involved light chain greater or equal to 10mg/dL provided serum FLC ratio is abnormal
- Bone marrow plasma cells greater than or equal to 30% total bone marrow cells
- >2 weeks since prior radiation therapy or systemic therapy at the time of leukapheresis.
- Total bilirubin ≤ 1.5 mg/dL (except in patients with Gilbert's syndrome).
- AST (SGOT)/ALT ≤ 2.5 X institutional upper limit of normal.
- Serum creatinine < 2 mg/dL.
- Cardiac ejection fraction of >45%, and no evidence of pericardial effusion, as determined by an echocardiogram.
- Adequate pulmonary function as defined as pulse oximetry ≥ 92% on room air.
- Subjects (or legal guardians) must have the ability to understand and the willingness to sign a written informed consent document.
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for at least 90 days after the BAFF CAR-T cell infusion.
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm
Who cannot join
- ASCT within 6 weeks of informed consent.
- History of allogeneic hematopoietic stem cell transplantation.
- Active graft-versus-host disease.
- Active central nervous system or meningeal involvement by myeloma. Subjects with untreated brain metastases/CNS disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with a history of CNS or meningeal involvement must be in a documented remission by CSF evaluation and contrast-enhanced MRI imaging for at least 90 days prior to registration.
- Active malignancy, other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast).
- Less than 28 days elapsed between prior treatment with investigational agent(s) and the day of lymphocyte collection.
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- New York Heart Association class IV congestive heart failure.
- Cardiovascular disorders including unstable angina pectoris, clinically significant cardiac arrhythmias, myocardial infarction or stroke (including transient ischemic attack, or other ischemic event) within 6 months prior to registration.
- Active infection requiring intravenous systemic treatment.
- HIV seropositivity.
- Pregnant or breastfeeding women are excluded from this study because LMY-920 therapy may be associated with the potential for teratogenic or abortifacient effects. Women of childbearing potential must have a negative serum pregnancy test. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with LMY-920, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study.
- Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy.
- Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.)
- Patients with history of clinically relevant CNS pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease.
- Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations that would limit compliance with study requirements.
- Known additional malignancies which require systemic treatment.
- History of autoimmune disease (i.e. rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medications (other than low dose steroids) within 6 months.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
University Hospitals Seidman Cancer Center
Cleveland, Ohio, 44106
Leland Metheny, MD, 2168440139, Leland.Metheny@uhhospitals.org
About this study
Official title: LUMT1A22, Phase 1 Study of BAFF CAR T Cells (LMY-920) for Treatment of Relapsed or Refractory Myeloma (LMY-920-002)
Since CAR-T cell treatment of refractory myeloma has shown success, based on preclinical data, we posit that CAR-T cells expressing B-cell activating factor (BAFF) can become another strategy to treat refractory myeloma, even after relapse following BCMA targeting CAR-T cell treatment. This will be phase 1 study of BAFF ligand CAR-T cells in relapsed and refractory myeloma.
Read the detailed description
In this open label, dose escalation study, up to four dose levels of autologous BAFF ligand CAR-T cells (LMY-920) will be evaluated for treatment relapsed and refractory myeloma. BAFF receptor family includes B-cell activating factor receptor (BR3), B-cell maturation antigen (BCMA) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI). The maximum tolerated dose (MTD) of LMY-920 will be determined using dose-escalation 3+3 design. The primary goal of this study is to determine recommended phase II dose of human LMY-920 in patients with relapsed or refractory myeloma.
- Being tested
- Autologous CAR-T cell therapy expressing the BAFF-ligand.
- Keywords
- multiple myeloma, CAR-T, BAFF ligand
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous CAR-T cell therapy expressing the BAFF-ligand.Biological
LMY-920
| Study group | Role | What they receive |
|---|---|---|
| LMY-920 dose escalation | Experimental | Open label, dose escalation study with up to four dose levels of LMY-920. The maximum tolerated dose (MTD) of LMY-920 will be determined using dose-escalation 3+3 design. Receives: Biological: Autologous CAR-T cell therapy expressing the BAFF-ligand. |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine recommended phase II dose of human LMY-920 in patients with relapsed or refractory myeloma.
Maximum tolerated dose
Measured: 24 months
Secondary outcomes (8)
To establish toxicity profile for the infusion of LMY-920.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0. All adverse events during study will be collected, categorized, and graded. Attribution of relatedness to the investigational agent will be assigned.
Measured: 24 months
To determine the objective response rate per International Myeloma Working Group uniform response criteria after treatment with LMY-920 in patients with relapsed or refractory myeloma.
Response rate.
Measured: 24 months
To determine the complete response rate per International Myeloma Working Group uniform response criteria after treatment with LMY-920 in patients with relapsed or refractory myeloma.
Response rate.
Measured: 24 months
To determine the duration of response.
Duration of response
Measured: 24 months
To determine the progression-free survival.
Progression-free survival
Measured: 24 months
To determine the overall survival
Overall survival
Measured: 24 months
To determine incidence of adverse events
Incidence of adverse events
Measured: 24 months
To determine incidence of anti- LMY-920 antibodies
Incidence of anti- LMY-920 antibodies
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2022
- Study start13 Mar 2024
- Primary completion31 Jul 2025 (estimated)
- Study completion31 Oct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple Myeloma, RefractoryStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- Open label, dose escalation study with up to four dose levels of LMY-920. The maximum tolerated dose (MTD) of LMY-920 will be determined using dose-escalation 3+3 design.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Luminary Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- The Cleveland Clinic, Case Western Reserve University
- Responsible party
- Sponsor
- Investigators
- Leland Metheny, MD, Principal investigator, University Hospitals Seidman Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05546723
- Sponsor's protocol ID
- LMY-920-002
- Other IDs
- LUMT1A22
- Acronym
- LMY-920-002
- Status last verified
- Oct 2024
- First submitted
- 15 Sep 2022
- Last updated
- 18 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- LUMT1A22, Phase 1 Study of BAFF CAR T Cells (LMY-920) for Treatment of Relapsed or Refractory Myeloma (LMY-920-002)
- ClinicalTrials.gov ID
- NCT05546723
- Acronym / sponsor ID
- LMY-920-002 / LMY-920-002
- Keywords
- multiple myeloma, CAR-T, BAFF ligand
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Luminary TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- The Cleveland Clinic, Case Western Reserve University
- Study start
- 13 Mar 2024 (actual)
- Primary completion
- 31 Jul 2025 (estimated)
- Study completion
- 31 Oct 2025 (estimated)
- First posted
- 21 Sep 2022 (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.
Since CAR-T cell treatment of refractory myeloma has shown success, based on preclinical data, we posit that CAR-T cells expressing B-cell activating factor (BAFF) can become another strategy to treat refractory myeloma, even after relapse following BCMA targeting CAR-T cell treatment. This will be phase 1 study of BAFF ligand CAR-T cells in relapsed and refractory myeloma.
Detailed description
In this open label, dose escalation study, up to four dose levels of autologous BAFF ligand CAR-T cells (LMY-920) will be evaluated for treatment relapsed and refractory myeloma. BAFF receptor family includes B-cell activating factor receptor (BR3), B-cell maturation antigen (BCMA) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI). The maximum tolerated dose (MTD) of LMY-920 will be determined using dose-escalation 3+3 design. The primary goal of this study is to determine recommended phase II dose of human LMY-920 in patients with relapsed or refractory myeloma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open label, dose escalation study with up to four dose levels of LMY-920. The maximum tolerated dose (MTD) of LMY-920 will be determined using dose-escalation 3+3 design.
| Arm | Type | Receives |
|---|---|---|
| LMY-920 dose escalation | Experimental | Biological: Autologous CAR-T cell therapy expressing the BAFF-ligand.Open label, dose escalation study with up to four dose levels of LMY-920. The maximum tolerated dose (MTD) of LMY-920 will be determined using dose-escalation 3+3 design. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Subjects must have histologically confirmed myeloma relapsed or refractory after 3 or more lines of therapy including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody. Failing line of therapy is defined accordingly to International Myeloma Workshop Consensus Panel.
- No evidence of CNS myeloma.
- Male or female > 18 years of age.
- ECOG Performance status ≤ 2.
- Has measurable disease at the time of enrollment as defined by at least one of the following:
Key exclusion criteria (17 listed)
- ASCT within 6 weeks of informed consent.
- History of allogeneic hematopoietic stem cell transplantation.
- Active graft-versus-host disease.
- Active central nervous system or meningeal involvement by myeloma. Subjects with untreated brain metastases/CNS disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with a history of CNS or meningeal involvement must be in a documented remission by CSF evaluation and contrast-enhanced MRI imaging for at least 90 days prior to registration.
- Active malignancy, other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast).
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 |
|---|---|---|
| Autologous CAR-T cell therapy expressing the BAFF-ligand.LMY-920 | Biological | LMY-920 dose escalation |
Primary outcome
To determine recommended phase II dose of human LMY-920 in patients with relapsed or refractory myeloma.
Time frame: 24 months
Maximum tolerated dose
8 secondary outcomes
To establish toxicity profile for the infusion of LMY-920.
Time frame: 24 months
To determine the objective response rate per International Myeloma Working Group uniform response criteria after treatment with LMY-920 in patients with relapsed or refractory myeloma.
Time frame: 24 months
To determine the complete response rate per International Myeloma Working Group uniform response criteria after treatment with LMY-920 in patients with relapsed or refractory myeloma.
Time frame: 24 months
To determine the duration of response.
Time frame: 24 months
To determine the progression-free survival.
Time frame: 24 months
To determine the overall survival
Time frame: 24 months
To determine incidence of adverse events
Time frame: 24 months
To determine incidence of anti- LMY-920 antibodies
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2024.
- Individual participant dataSharing planned: No
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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.
Leland Metheny, MD principal investigator
University Hospitals Seidman Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Autologous CAR-T cell therapy expressing the BAFF-ligand. in people with Multiple Myeloma, Refractory and Multiple Myeloma in Relapse, run by Luminary Therapeutics at 1 site in United States.
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 18 inclusion and 17 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 18 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 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.
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?
Contact Leland Metheny, MD ((216) 844-0139, Leland.Metheny@uhhospitals.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine recommended phase II dose of human LMY-920 in patients with relapsed or refractory myeloma. (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Oct 2024.