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

NCT06916767 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CASE3424
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Relapsed CLL; Refractory CLL; Refractory Lymphoma

Keywords

BAFF CAR-T cells

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of LMY-920

  28 days after the day of infusion (day 0) of LMY-920 or until death, whichever occurs first

Secondary Outcomes (8)

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  1 month after LMY-920 therapy

• Objective response rate(ORR)

  12 months after LMY-920 therapy

• Complete response rate(CRR)

  12 months after LMY-920 therapy

• Duration of response(DOR) rate

  12 months after LMY-920 therapy

• Progression free survival (PFS)

  12 months after LMY-920 therapy

Study Arms (1)

LMY-920 dose escalation

EXPERIMENTAL

Drug: BAFF CAR-T; Drug: Obinutuzumab; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

BAFF CAR-T DRUG

Single infusion

LMY-920 dose escalation

Obinutuzumab DRUG

IV administered

LMY-920 dose escalation

Cyclophosphamide DRUG

500mg/m2 on days -5 to -3

LMY-920 dose escalation

Fludarabine DRUG

30mg/m2 daily on days -5 to -3

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:

• 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.
• No evidence of CNS lymphoma.
• Male or female ≥ 18 years of age.
• ECOG Performance status ≤ 2 \[See Appendix 1\].
• 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.
• 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 (ie, ECOG performance scale 2 or worse; cannot work or unable to perform usual activities).
• Fevers ≥100.5°F or 38.0°C for 2 or more weeks without evidence of infection.

You may not qualify if:

• The presence of any of the following will exclude a participant from study enrollment:
• 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. 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.
• Active malignancy, other than non-melanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, breast).
• 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).
• 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 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.
• 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. Participants 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 participants will be excluded.)

Sponsors & Collaborators

• Paolo Caimi, MD: lead
• The Leukemia and Lymphoma Society: collaborator

Study Sites (1)

Case Comprehensive Cancer Center, Cleveland Clinic Foundation Taussig Cancer Institute

Cleveland, Ohio, 44195, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma

Interventions

obinutuzumab; Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Paolo Caimi, MD

  Case Comprehensive Cancer Center, Cleveland Clinic Taussig Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paolo Caimi, MD

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 1, 2025
• First Posted: April 8, 2025
• Study Start: July 15, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: November 10, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data included in the peer reviewed publication will be publicly available indefinitely. No raw data will be shared.
• Access Criteria: A peer-reviewed publication will be made available according to the publishing journal's specifications. CCF personnel will not share study data apart from that which has been published publicly

Locations

US (1)