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

Official title

LMY-920 for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma

Overview

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.

Detailed description

LMY-920 is an autologous CAR-T cell therapy consisting of autologous cluster of differentiation 4 (CD4) positive and cluster of differentiation 8 (CD8) positive human T cells that are genetically engineered using the non-viral transposon system to express the BAFF-ligand CAR-T that target BAFF receptor family members to eliminate malignant B cells.

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). These receptors are present on non-Hodgkin lymphoma.

The goal of LMY-920-001 phase 1 study is to find recommended phase 2 dose of LMY-920 for treatment of patients with relapsed or refractory non-Hodgkin lymphoma.

Interventions

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

Primary outcome measures

• To determine recommended phase II dose of human LMY-920. [Time frame: 24 months]

Secondary outcome measures (8)

• To establish toxicity profile for the infusion of LMY-920. [Time frame: 24 months]
• To determine the objective response rate . [Time frame: 24 months]
• To determine the complete response rate. [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]

Eligibility criteria

Inclusion criteria

• 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.

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 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.
• Known additional malignancies which require systemic treatment.
• History of autoimmune disease with requirement of immunosuppressive medications (other than low dose steroids) within 6 months.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 2 centers

• University Hospitals Seidman Cancer Center — Cleveland
• Taussig Cancer Institute | Cleveland Clinic — Cleveland

Identifiers

NCT: NCT05312801 · LMY-920-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗