BAFF CAR-T Cells (LMY-922) for Treatment of Refractory Hematologic Malignancies
A Phase 1 Study of Allogeneic (γ/δ) BAFF CAR-T Cells (LMY-922) for Treatment of Refractory Hematologic Malignancies
1 other identifier
interventional
27
1 country
1
Brief Summary
Therapy with chimeric antigen receptor T (CAR-T) cells has demonstrated activity against refractory hematologic malignancies, 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 hematologic malignancies, 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 refractory hematologic malignancies using a single lymphodepletion regimen and using a BAFF CAR-T cell manufacturing process.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Sep 2026
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 22, 2026
CompletedFirst Posted
Study publicly available on registry
July 1, 2026
CompletedStudy Start
First participant enrolled
September 1, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2029
Study Completion
Last participant's last visit for all outcomes
April 1, 2029
July 1, 2026
June 1, 2026
2.6 years
June 22, 2026
June 25, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
To assess the safety profile of LMY-922 in patients with refractory hematologic malignancies.
Incidence and severity of treatment-emergent adverse events
12 Months
To determine the Recommended Phase II Dose of LMY-922 in patients with refractory hematologic malignancies.
Incidence of dose limiting toxicities (DLT)
12 Months
Secondary Outcomes (4)
Response rates for each malignancy
12 Months
Progression free survival (PFS) for each malignancy
12 Months
Duration of response for each malignancy
12 Months
Overall survival (OS) for each malignancy
12 Months
Other Outcomes (12)
CAR-T cell expansion and persistence
12 Months
Changes in serum concentration of cytokines
12 Months
Expression of BR3 on tumor cells
12 Months
- +9 more other outcomes
Study Arms (12)
Non-Hodgkin Lymphoma: LMY-922 Dose Level -1
EXPERIMENTALDose Level -1 of 75 million BAFF+ CAR cells for the non-Hodgkin lymphoma group of an open label, dose escalation study with up to four dose levels of LMY-922. The maximum tolerated dose of LMY-922 will be determined using dose-escalation 3+3 design.
Non-Hodgkin Lymphoma: LMY-922 Dose Level 1
EXPERIMENTALDose Level 1 of 150 million BAFF+ CAR cells for the non-Hodgkin lymphoma group of an open label, dose escalation study with up to four dose levels of LMY-922. The maximum tolerated dose of LMY-922 will be determined using dose-escalation 3+3 design.
Non-Hodgkin Lymphoma: LMY-922 Dose Level 2
EXPERIMENTALDose Level 2 of 300 million BAFF+ CAR cells for the non-Hodgkin lymphoma group of an open label, dose escalation study with up to four dose levels of LMY-922. The maximum tolerated dose of LMY-922 will be determined using dose-escalation 3+3 design.
Non-Hodgkin Lymphoma: LMY-922 Dose Level 3
EXPERIMENTALDose Level 3 of 450 million BAFF+ CAR cells for the non-Hodgkin lymphoma group of an open label, dose escalation study with up to four dose levels of LMY-922. The maximum tolerated dose of LMY-922 will be determined using dose-escalation 3+3 design.
Chronic Lymphocytic Leukemia / Hairy Cell Leukemia: LMY-922 Dose Level -1
EXPERIMENTALDose Level -1 of 75 million BAFF+ CAR cells for the Chronic Lymphocytic Leukemia / Hairy Cell Leukemia group of an open label, dose escalation study with up to four dose levels of LMY-922. The maximum tolerated dose of LMY-922 will be determined using dose-escalation 3+3 design.
Chronic Lymphocytic Leukemia / Hairy Cell Leukemia: LMY-922 Dose Level 1
EXPERIMENTALDose Level 1 of 150 million BAFF+ CAR cells for the Chronic Lymphocytic Leukemia / Hairy Cell Leukemia group of an open label, dose escalation study with up to four dose levels of LMY-922. The maximum tolerated dose of LMY-922 will be determined using dose-escalation 3+3 design.
Chronic Lymphocytic Leukemia / Hairy Cell Leukemia: LMY-922 Dose Level 2
EXPERIMENTALDose Level 2 of 300 million BAFF+ CAR cells for the Chronic Lymphocytic Leukemia / Hairy Cell Leukemia group of an open label, dose escalation study with up to four dose levels of LMY-922. The maximum tolerated dose of LMY-922 will be determined using dose-escalation 3+3 design.
Chronic Lymphocytic Leukemia / Hairy Cell Leukemia: LMY-922 Dose Level 3
EXPERIMENTALDose Level 3 of 450 million BAFF+ CAR cells for the Chronic Lymphocytic Leukemia / Hairy Cell Leukemia group of an open label, dose escalation study with up to four dose levels of LMY-922. The maximum tolerated dose of LMY-922 will be determined using dose-escalation 3+3 design.
Multiple Myeloma: LMY-922 Dose Level -1
EXPERIMENTALDose Level -1 of 75 million BAFF+ CAR cells for the Multiple Myeloma group of an open label, dose escalation study with up to four dose levels of LMY-922. The maximum tolerated dose of LMY-922 will be determined using dose-escalation 3+3 design.
Multiple Myeloma: LMY-922 Dose Level 1
EXPERIMENTALDose Level 1 of 150 million BAFF+ CAR cells for the Multiple Myeloma group of an open label, dose escalation study with up to four dose levels of LMY-922. The maximum tolerated dose of LMY-922 will be determined using dose-escalation 3+3 design.
Multiple Myeloma: LMY-922 Dose Level 2
EXPERIMENTALDose Level 2 of 300 million BAFF+ CAR cells for the Multiple Myeloma group of an open label, dose escalation study with up to four dose levels of LMY-922. The maximum tolerated dose of LMY-922 will be determined using dose-escalation 3+3 design.
Multiple Myeloma: LMY-922 Dose Level 3
EXPERIMENTALDose Level 3 of 450 million BAFF+ CAR cells for the Multiple Myeloma group of an open label, dose escalation study with up to four dose levels of LMY-922. The maximum tolerated dose of LMY-922 will be determined using dose-escalation 3+3 design.
Interventions
Allogeneic CAR-T cell therapy expressing the BAFF-ligand
Eligibility Criteria
You may qualify if:
- \. Male or female 18-75 years of age. 2. Patient with:
- a. NHL: Histologically confirmed B cell NHL (including but not limited to diffuse large B cell lymphoma (DLBCL), follicular lymphoma, MCL, marginal zone lymphoma (MZL)) i. Relapsed after 2 or more lines of therapy, or ii. Have disease refractory to prior 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), and iii. Measurable disease per Lugano Revised Response Criteria for Malignant Lymphoma
- b. CLL: histologically confirmed CLL i. Relapsed after 2 or more lines of therapy ii. Previous therapies prescribed must have included a Bruton's tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL2) inhibitor, iii. Measurable disease and active disease: Active disease as defined by the iwCLL criteria, meeting at least one of the following criteria:
- Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia. Cutoff levels of Hb \<10 g/dL or platelet counts \<100 × 10\^9/L are generally regarded as indication for treatment.
- Massive (i.e., ≥6 cm below the left costal margin) or progressive or symptomatic splenomegaly.
- Massive nodes (i.e., ≥10 cm in longest diameter) or progressive or symptomatic lymphadenopathy.
- Symptomatic or functional extranodal involvement (e.g., skin, kidney, lung, spine, etc.).
- Disease-related symptoms as defined by any of the following:
- Unintentional weight loss ≥10% within the previous 6 months.
- Significant fatigue (i.e., Eastern Cooperative Oncology Group (ECOG) performance scale 2 or worse; cannot work or unable to perform usual activities).
- Fevers ≥ 38.0°C for 2 or more weeks without evidence of infection.
- Night sweats for ≥1 month without evidence of infection.
- c. HCL: histologically confirmed HCL i. Relapsed after at least one line of therapy, which must have included a purine nucleoside (eg. fludarabine, cladribine or pentostatin) and moxetumomab pasudotox.
- ii. Need for treatment as evidenced by any one of the following: Absolute Neutrophil Count (ANC) \<1 × 10\^3/mcL, Hb \<10g/dL, platelet count \<100 × 10\^3/mcL, leukemia cell count \>5 × 10\^3/mcL, symptomatic splenomegaly, or enlarging HCL mass \>2 cm in short axis.
- d. MM: histologically confirmed MM i. Relapsed or refractory after 3 or more lines of therapy including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody.
- +15 more criteria
You may not qualify if:
- Second active (i.e., currently requires antineoplastic therapy) non-B cell lineage malignancy, other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast).
- Renal failure requiring regular dialysis.
- Uncontrolled pulmonary disease or infection.
- Cardiovascular disorders including symptomatic congestive heart failure, 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 systemic treatment.
- HIV seropositive with a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within 12 months of enrollment, or has not been on an established antiretroviral therapy (ART) for at least four weeks with an HIV viral load less than 400 copies/mL.
- Pregnant or breastfeeding women are excluded from this study (breastfeeding should be discontinued), because there is an unknown, but potential risk for adverse events in fetuses and nursing infants secondary to treatment of the mother with LMY-922 and lymphodepleting chemotherapy. Women of childbearing potential must have a negative serum pregnancy test.
- 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 central nervous system (CNS) pathology such as uncontrolled epilepsy, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia, and Parkinson's disease.
- Subjects with uncontrolled intercurrent or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients receiving a live vaccine within 2 weeks prior to screening.
- Concurrent use of high dose systemic steroids and/or immunosuppressive therapies.
- Steroid dose must be weaned to ≤10 mg/day prednisone equivalent prior to CAR-T cell infusion.
- Immunosuppressive medications must be stopped at least 5 half-lives prior to CAR-T cell infusion.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Taussig Cancer Institute | Cleveland Clinic
Cleveland, Ohio, 44195, United States
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 22, 2026
First Posted
July 1, 2026
Study Start (Estimated)
September 1, 2026
Primary Completion (Estimated)
April 1, 2029
Study Completion (Estimated)
April 1, 2029
Last Updated
July 1, 2026
Record last verified: 2026-06
Data Sharing
- IPD Sharing
- Will not share