LMY-920 for Treatment of Relapsed or Refractory Myeloma

NCT05546723 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: LMY-920-002LUMT1A22
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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. This will be phase 1 study of BAFF ligand CAR-T cells in relapsed and refractory myeloma.

Conditions

Multiple Myeloma, Refractory; Multiple Myeloma in Relapse

Keywords

multiple myeloma; CAR-T; BAFF ligand

Outcome Measures

Primary Outcomes (1)

• To determine recommended phase II dose of human LMY-920 in patients with relapsed or refractory myeloma.

  Maximum tolerated dose

  24 months

Secondary Outcomes (8)

• To establish toxicity profile for the infusion of LMY-920.

  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.

  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.

  24 months

• To determine the duration of response.

  24 months

• To determine the progression-free survival.

  24 months

Study Arms (1)

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.

Biological: Autologous CAR-T cell therapy expressing the BAFF-ligand.

Interventions

Autologous CAR-T cell therapy expressing the BAFF-ligand. BIOLOGICAL

LMY-920

LMY-920 dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Luminary Therapeutics: lead
• The Cleveland Clinic: collaborator
• Case Western Reserve University: collaborator

Study Sites (1)

University Hospitals Seidman Cancer Center

Cleveland, Ohio, 44106, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Leland Metheny, MD

  University Hospitals Seidman Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Leland Metheny, MD

CONTACT

(216) 844-0139; Leland.Metheny@uhhospitals.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 15, 2022
• First Posted: September 21, 2022
• Study Start: March 13, 2024
• Primary Completion: July 31, 2025
• Study Completion: October 31, 2025
• Last Updated: October 18, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)