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RECRUITINGPHASE1

Phase 1 Study of BAFF CAR-T Cells (LMY-920) for Treatment of Relapsed or Refractory Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma

NCT06916767•Paolo Caimi, MD

Summary

CAR-T cell treatment of refractory lymphoma has shown success, particularly with CD-19 targeted CAR-T cells, however, many participants are refractory or relapse after response. Responses are more limited in CLL/SLL, possibly secondary to the suppressive effect of circulating B cells on T cell function. BAFF receptor is a target that has been explored in CLL. Preclinical data indicates that CAR- T cells expressing B-cell activating factor (BAFF) can be another effective strategy to treat refractory CLL. This study aims to explore the efficacy of LMY-920 a BAFF-ligand CAR T cells with depletion of B cells with Obinutuzumab prior to apheresis.

Detailed Description

There is a persistent need for development of new, effective therapies for treatment of B cell malignancies. Therapy with CAR-T cells has demonstrated activity against refractory lymphoma, however not all tumors respond or remain in response to CD19 targeted CAR-T cells. While CAR T-cells have activity against CLL/SLL, the rates of response are more limited than non Hodgkin lymphoma. Based on preclinical data of anti BAFF-R CAR T-cells13 as well as preclinical and early phase studies using anti-BAFF-R monoclonal antibodies in CLL) investigators posit that CAR-T cells expressing BAFF (BAFF CAR-T cells, LMY-920 can become another strategy to treat refractory CLL. This study will evaluate the safe dose and provide initial signal of the activity of BAFF CAR- T cells against relapsed CLL/SLL using a single lymphodepletion regimen and using a BAFF CAR-T cell manufacturing process that can be replicated in multiple academic institutions with the appropriate cellular manufacturing facilities.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Histologically confirmed chronic lymphocytic leukemia (including small lymphocytic lymphoma)
•* Relapsed after 2 or more lines of therapy, including a BTK inhibitor and a BCL2 inhibitor.
•2. No evidence of CNS lymphoma.
•3. Male or female ≥ 18 years of age.
•4. ECOG Performance status ≤ 2 \[See Appendix 1\].
•5. Presence of Presence of active disease for participants with CLL and SLL and presence of measurable disease for participants with SLL.
•A. CLL/SLL (note that SLL participants must have both measurable disease and active disease): Active disease as defined by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL), with at least one of the following criteria21:
•* 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 × 109/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.
+20 more criteria

Exclusion Criteria

•The presence of any of the following will exclude a participant from study enrollment:
•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 lymphoma or leukemia. Participants 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. participants 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. Known active additional malignancies which require systemic treatment (non-immediately morbid malignancies receiving only low-toxicity regimens such as hormone suppression for prostate or breast cancer may be allowed at the judgment of the investigator).
•7. Less than 28 days elapsed between prior treatment with investigational agent(s) and the day of lymphocyte collection.
•8. New York Heart Association class IV congestive heart failure.
•9. 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.
+30 more criteria

Locations (1)

Case Comprehensive Cancer Center, Cleveland Clinic Foundation Taussig Cancer Institute

Cleveland, Ohio, United States

Key Dates

Start Date

July 15, 2025

Primary Completion Date

December 31, 2027

Completion Date

December 31, 2027

Last Updated

November 10, 2025

Enrollment

ESTIMATED participants

Conditions

Relapsed CLLRefractory CLLRefractory Lymphoma

Interventions

BAFF CAR-T

DRUG

Obinutuzumab

DRUG

Cyclophosphamide

DRUG

Fludarabine

DRUG

Contacts

Paolo Caimi, MD

CONTACT

1-866-223-8100 TaussigResearch@ccf.orgarch@ccf.org

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: November 10, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Phase 1 Study of BAFF CAR-T Cells (LMY-920) for Treatment of Relapsed or Refractory Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma

Inclusion Criteria

Exclusion Criteria

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