A Study of MB-CART19.1 Cellular Therapy for People With Central Nervous System Lymphoma (CNSL)

NCT07137494 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 25-066
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 7

Brief Summary

This study will test whether MB-CART19.1 is a safe and effective treatment for central nervous system lymphoma (CNSL). This study will test different doses of MB-CART19.1 to find the highest dose that causes few or mild side effects in participants.

Conditions

Primary Central Nervous System (CNS) Lymphoma; Secondary Central Nervous System Lymphoma

Keywords

MB-CART19.1 Cellular Therapy; Relapsed/Refractory; CliniMACS Prodigy Device

Outcome Measures

Primary Outcomes (1)

• To identify the maximum tolerated dose (MTD)

  The maximum tolerated dose (MTD) is defined as the highest dose level where a Dose limiting toxicity (DLT) occurs within at most one out of six patients treated. DLT is defined as any of the following adverse events (AEs) that occur within 28 days of the MB-CART19.1 infusion, based on Common Terminology Criteria for Adverse Events (CTCAE) v5.0, TIAN grading65, or the ASTCT Consensus Grading guidelines for Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity (ICANS).

  1 year

Study Arms (1)

MB-CART19.1 Cellular Therapy

EXPERIMENTAL

Following enrollment, patients will undergo leukapheresis of peripheral blood for mononuclear cell collection, followed by further T cell enrichment, activation and genetic modification using a lentiviral vector encoding a CD19 targeted CAR. These T cells will be expanded and after the appropriate number of cells is generated, the modified T cells may be infused fresh or frozen for later use according to standard operating procedures. Modified T cell infusions will be administered 2-7 days following completion of the conditioning chemotherapy. Serial sampling of blood and cerebrospinal fluid (CSF) will be performed following treatment to assess toxicity, therapeutic effects, and survival of the genetically modified T cells.

Biological: MB-CART19.1 Cellular Therapy

Interventions

MB-CART19.1 Cellular Therapy BIOLOGICAL

MB-CART19.1 will be infused as a single infusion during an inpatient admission.

MB-CART19.1 Cellular Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women who are at least 18 years of age on the day of consenting to the study.
• Histologically documented primary or secondary central nervous system lymphoma of DLBCL subtype
• Relapsed/refractory primary or secondary CNSL patients. All relapsed//refractory patients need to have received at least one prior CNS-directed methotrexate-based therapy. There is no restriction on the number of recurrences.
• For relapsed patients, parenchymal lesions must have unequivocal evidence of disease progression on imaging (MRI of the brain or head CT) within 21 days of study consent.
• For refractory patients, there must be residual disease after their last line of therapy.
• For patients with leptomeningeal disease only, CSF cytology and/or flow cytometry must document CSF findings consistent with CSF involvement by lymphoma and/or imaging findings consistent with CSF disease within 21 days of study registration (at the discretion of the investigator).
• Creatinine Clearance ≥ 40 ml/min/m2, direct bilirubin ≤2.0 mg/100 ml, AST and ALT ≤3.0x upper limit of normal (ULN)
• Adequate pulmonary function as assessed by ≥90% oxygen saturation on room air by pulse oximetry.
• Must be able to tolerate both MRI and CT scans
• Must be able to tolerate lumbar puncture and/or Ommaya taps
• Must have been either off corticosteroids, or on a stable or decreasing dose of dexamethasone equivalent ≤ 2 mg daily for 7 days before apheresis and 72 hours prior to CAR T cell infusion o Use of corticosteroids to treat CAR T cell toxicities per MSKCC guidelines is permitted

You may not qualify if:

• ECOG performance status \>2
• o Patients with ECOG status of 2 will be enrolled at the discretion of the PI
• Active systemic lymphoma (i.e. involvement outside of the CNS)
• If the most recent CSF or brain tissue sample demonstrates absence of CD19 expression
• Size of any single CNS lymphoma lesion exceeds 3 cm in maximal diameter in eloquent brain structures.
• Prior treatment of systemic lymphoma with CD19-targeted CAR T cells
• Pregnant or lactating patients. Patients of childbearing age should use effective contraception while on this study and continue for 1 year after all treatment is finished.
• Impaired cardiac function (LVEF \<40%) as assessed by most recent ECHO in the last 1 year.
• Patients with autoimmune disease requiring systemic T cell-suppressive therapy.
• Patients with following cardiac conditions will be excluded:
• New York Heart Association (NYHA) stage III or IV congestive heart failure
• Myocardial infarction ≤6 months prior to enrollment
• History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration ≤6 months prior to enrollment
• Patients with ocular lymphoma in the absence of other CNS involvement
• Patient has received chemotherapy, monoclonal antibodies or targeted anticancer therapy ≤ 4 weeks or 5 half-lives, whichever is shorter, or 6 weeks for nitrosourea or mitomycin-C, or 3 months since allogeneic hematopoietic stem cell transplantation, prior to starting the study drug, or the patient has not recovered from the side effects of such therapy.

Sponsors & Collaborators

• Miltenyi Biomedicine GmbH: collaborator
• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering at Basking Ridge (All Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering at Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering at Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering at Suffolk-Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering at Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering at Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lymphoma; Recurrence

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ivan Kotchetkov, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ivan Kotchetkov, MD

CONTACT

212-610-0751; kotcheti@mskcc.org

Maria Palomba, MD

CONTACT

646-608-3711

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: It is modeled on a 3+3 design.

Study Record Dates

• First Submitted: August 15, 2025
• First Posted: August 22, 2025
• Study Start: August 14, 2025
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (7)