LMY-920 for Treatment of Relapsed or Refractory Myeloma

NCT ID: NCT05546723

Last Updated: 2024-10-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-13
• Study Completion Date: 2025-10-31

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.

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.

Conditions

Multiple Myeloma, Refractory; Multiple Myeloma in Relapse

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

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

Intervention Type: BIOLOGICAL

LMY-920

Interventions

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

LMY-920

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. 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.

2. No evidence of CNS myeloma.

3. Male or female > 18 years of age.

4. ECOG Performance status ≤ 2.

5. 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

6. >2 weeks since prior radiation therapy or systemic therapy at the time of leukapheresis.

7. Total bilirubin ≤ 1.5 mg/dL (except in patients with Gilbert's syndrome).

8. AST (SGOT)/ALT ≤ 2.5 X institutional upper limit of normal.

9. Serum creatinine < 2 mg/dL.

10. Cardiac ejection fraction of >45%, and no evidence of pericardial effusion, as determined by an echocardiogram.

11. Adequate pulmonary function as defined as pulse oximetry ≥ 92% on room air.

12. Subjects (or legal guardians) must have the ability to understand and the willingness to sign a written informed consent document.

13. 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.

14. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm

Exclusion Criteria

1. ASCT within 6 weeks of informed consent.

2. History of allogeneic hematopoietic stem cell transplantation.

3. Active graft-versus-host disease.

4. 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.

5. Active malignancy, other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast).

6. Less than 28 days elapsed between prior treatment with investigational agent(s) and the day of lymphocyte collection.

7. New York Heart Association class IV congestive heart failure.

8. 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.

9. Active infection requiring intravenous systemic treatment.

10. HIV seropositivity.

11. 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.

12. Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy.

13. 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.)

14. 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.

15. 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.

16. Known additional malignancies which require systemic treatment.

17. History of autoimmune disease (i.e. rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medications (other than low dose steroids) within 6 months.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Luminary Therapeutics

INDUSTRY

Sponsor Role: lead

The Cleveland Clinic

OTHER

Sponsor Role: collaborator

Case Western Reserve University

OTHER

Sponsor Role: collaborator

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Leland Metheny, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospitals Seidman Cancer Center

Locations

University Hospitals Seidman Cancer Center

Cleveland, Ohio, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Leland Metheny, MD

Role: CONTACT

Leland.Metheny@uhhospitals.org

(216) 844-0139

Facility Contacts

Leland Metheny, MD

Role: primary

Leland.Metheny@uhhospitals.org

2168440139

Other Identifiers

LUMT1A22

Identifier Type: OTHER

Identifier Source: secondary_id

LMY-920-002

Identifier Type: -

Identifier Source: org_study_id