BAFF CAR-T Cells (LMY-922) for Treatment of Refractory Hematologic Malignancies

ConditionsNon-Hodgkin Lymphoma Chronic Lymphocytic Leukemia Hairy Cell Leukemia Multiple Myeloma

Trial statusNot yet recruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexAll

Age18-75

SponsorLuminary Therapeutics

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.).

Disqualifiers

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.

Trial design

Design model

Sequential

Treatments tested in this trial

LMY-922
Biological/Vaccine
Allogeneic CAR-T cell therapy expressing the BAFF-ligand

Treatment groups

27 Participants

are divided into 12 treatment groups

Treatment groups

See each treatment group below.

Group A: Non-Hodgkin Lymphoma: LMY-922 Dose Level -1Experimental treatment 1 intervention

Group B: Non-Hodgkin Lymphoma: LMY-922 Dose Level 1Experimental treatment 1 intervention

Group C: Non-Hodgkin Lymphoma: LMY-922 Dose Level 2Experimental treatment 1 intervention

Group D: Non-Hodgkin Lymphoma: LMY-922 Dose Level 3Experimental treatment 1 intervention

Group E: Chronic Lymphocytic Leukemia / Hairy Cell Leukemia: LMY-922 Dose Level -1Experimental treatment 1 intervention

Group F: Chronic Lymphocytic Leukemia / Hairy Cell Leukemia: LMY-922 Dose Level 1Experimental treatment 1 intervention

Group G: Chronic Lymphocytic Leukemia / Hairy Cell Leukemia: LMY-922 Dose Level 2Experimental treatment 1 intervention

Group H: Chronic Lymphocytic Leukemia / Hairy Cell Leukemia: LMY-922 Dose Level 3Experimental treatment 1 intervention

Group I: Multiple Myeloma: LMY-922 Dose Level -1Experimental treatment 1 intervention

Group J: Multiple Myeloma: LMY-922 Dose Level 1Experimental treatment 1 intervention

Group K: Multiple Myeloma: LMY-922 Dose Level 2Experimental treatment 1 intervention

Group L: Multiple Myeloma: LMY-922 Dose Level 3Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

To assess the safety profile of LMY-922 in patients with refractory hematologic malignancies.

Incidence and severity of treatment-emergent adverse events

Time frame

12 Months

To determine the Recommended Phase II Dose of LMY-922 in patients with refractory hematologic malignancies.

Incidence of dose limiting toxicities (DLT)

Time frame

12 Months

Secondary outcomes

Response rates for each malignancy

NHL: per Lugano Revised Response Criteria for Malignant Lymphoma; CLL: per 2018 iwCLL criteria; HCL: per Consensus Guidelines for The Diagnosis and Management of Patients with Classic Hairy Cell Leukemia; MM: per IMWG uniform response criteria

Time frame

12 Months

Progression free survival (PFS) for each malignancy

Progression free survival

Time frame

12 Months

Duration of response for each malignancy

Duration of response

Time frame

12 Months

Overall survival (OS) for each malignancy

Overall survival

Time frame

12 Months

Other outcomes

CAR-T cell expansion and persistence

CAR-T cell expansion and persistence (described as maximum concentration (Cmax), time to maximum concentration (Tmax), area under the curve (AUC)s and other relevant pharmacokinetics (PK) parameters)

Time frame

12 Months

Changes in serum concentration of cytokines

Changes in serum concentration of cytokines and their correlation with toxicity and response.

Time frame

12 Months

Expression of BR3 on tumor cells

Expression of BR3 on tumor cells and the association with response

Time frame

12 Months

Serum soluble BR3

Serum soluble BR3 pre and post infusion and the correlation with clinical response

Time frame

12 Months

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Luminary Therapeutics

Lead sponsor

Source ClinicalTrials.gov

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