- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05546723
LMY-920 for Treatment of Relapsed or Refractory Myeloma (LMY-920-002)
March 13, 2024 updated by: Luminary Therapeutics
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.
Study Overview
Status
Recruiting
Intervention / Treatment
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 Type
Interventional
Enrollment (Estimated)
30
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Leland Metheny, MD
- Phone Number: (216) 844-0139
- Email: Leland.Metheny@uhhospitals.org
Study Locations
-
-
Ohio
-
Cleveland, Ohio, United States, 44106
- Recruiting
- University Hospitals Seidman Cancer Center
-
Contact:
- Leland Metheny, MD
- Phone Number: 216-844-0139
- Email: Leland.Metheny@uhhospitals.org
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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.
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: LMY-920 dose escalation
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.
|
LMY-920
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To determine recommended phase II dose of human LMY-920 in patients with relapsed or refractory myeloma.
Time Frame: 24 months
|
Maximum tolerated dose
|
24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To establish toxicity profile for the infusion of LMY-920.
Time Frame: 24 months
|
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.
|
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
|
Response rate.
|
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
|
Response rate.
|
24 months
|
To determine the duration of response.
Time Frame: 24 months
|
Duration of response
|
24 months
|
To determine the progression-free survival.
Time Frame: 24 months
|
Progression-free survival
|
24 months
|
To determine the overall survival
Time Frame: 24 months
|
Overall survival
|
24 months
|
To determine incidence of adverse events
Time Frame: 24 months
|
Incidence of adverse events
|
24 months
|
To determine incidence of anti- LMY-920 antibodies
Time Frame: 24 months
|
Incidence of anti- LMY-920 antibodies
|
24 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Leland Metheny, MD, University Hospitals Seidman Cancer Center
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 13, 2024
Primary Completion (Estimated)
July 31, 2025
Study Completion (Estimated)
October 31, 2025
Study Registration Dates
First Submitted
September 15, 2022
First Submitted That Met QC Criteria
September 15, 2022
First Posted (Actual)
September 21, 2022
Study Record Updates
Last Update Posted (Actual)
March 15, 2024
Last Update Submitted That Met QC Criteria
March 13, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
Other Study ID Numbers
- LMY-920-002
- LUMT1A22 (Other Identifier: Cleveland Clinic Taussig Cancer Institute)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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