Phase 1 Study of BAFF CAR-T Cells (LMY-920) for Non-Hodgkin Lymphoma

NCT05312801 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: LMY-920-001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

Therapy with chimeric antigen receptor T (CAR-T) cells has demonstrated activity against refractory lymphoma, however not all tumors respond or remain in response to CD19 targeted CAR-T cells. We posit that CAR-T cells expressing BAFF (BAFF CAR-T cells) can become another strategy to treat refractory lymphoma, even after relapse following cluster of differentiation antigen 19 (CD19) targeting CAR-T treatment. This phase 1 study will evaluate safe dose and provide initial signal of the activity of BAFF CAR-T cells against relapsed non-Hodgkin lymphoma using a single lymphodepletion regimen and using a BAFF CAR-T cell manufacturing process.

Conditions

Lymphoma, Non-Hodgkin Lymphoma, B-Cell

Keywords

non-Hodgkin lymphoma.

Outcome Measures

Primary Outcomes (1)

• To determine recommended phase II dose of human LMY-920.

  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 .

  24 months

• To determine the complete response rate.

  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.

Drug: BAFF CAR-T

Interventions

BAFF CAR-T DRUG

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

Also known as: 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 non-Hodgkin lymphoma relapsed after 2 or more lines of therapy or disease refractory to chemotherapy (defined as progressive disease or stable disease lasting ≤6 months, as best response to most recent chemotherapy regimen; or disease progression or recurrence ≤12 months after prior autologous stem cell transplantation (ASCT).
• No evidence of central nervous system (CNS) lymphoma.
• Male or female \> 18 years of age.
• Eastern Cooperative Oncology Group Performance status ≤ 2.
• At least one measurable lesion.
• \>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).
• Aspartate aminotransferase/alanine transferase ≤ 2.5 X institutional upper limit of normal.
• Serum creatinine \< 1.5 mg/dL.
• Cardiac ejection fraction of \>50%, 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.

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 lymphoma or leukemia.
• 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.
• 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 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.

Sponsors & Collaborators

• Luminary Therapeutics: lead
• Case Comprehensive Cancer Center: collaborator

Study Sites (2)

University Hospitals Seidman Cancer Center

Cleveland, Ohio, 44106, United States

NOT YET RECRUITING

Taussig Cancer Institute | Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Paolo F. Caimi, MD

  Cleveland Clinic Taussig Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paolo F. Caimi, MD

CONTACT

216 445-4635; CAIMIP@ccf.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. Dose Levels 1. 1 x 10 million BAFF+ CAR cells/kg 2. 2 x 10 million BAFF+ CAR cells/kg 3. 4 x 10 million BAFF+ CAR cells/kg 4. 8 x 10 million BAFF+ CAR cells/kg

Study Record Dates

• First Submitted: March 24, 2022
• First Posted: April 6, 2022
• Study Start: November 21, 2023
• Primary Completion: May 1, 2025
• Study Completion: September 2, 2025
• Last Updated: October 21, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)