MB-CART19.1 cellular therapy for people with central nervous system lymphoma

A Phase I Study of MB-CART19.1 Cellular Therapy for Relapsed/Refractory Primary and Secondary Central Nervous System Lymphoma (CNSL) Using On- Site Manufacturing With the CliniMACS Prodigy Device

This will test whether MB-CART19.1 cellular therapy is safe and helps adults with relapsed or refractory primary or secondary central nervous system lymphoma.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Memorial Sloan Kettering Cancer Center (other)
• Drugs / interventions: CAR T, chemotherapy, methotrexate
• Locations: 7 sites (Basking Ridge, New Jersey and 6 other locations)
• Trial ID: NCT07137494 on ClinicalTrials.gov

What this trial studies

This Phase 1, open-label dose-escalation trial gives MB-CART19.1 cellular therapy to adults with relapsed or refractory CNS lymphoma of the DLBCL subtype to identify the highest dose with acceptable side effects. Eligible participants must be at least 18, have histologically confirmed CNS lymphoma (DLBCL), and have received at least one prior methotrexate-based CNS-directed therapy, with disease documented by MRI, CT, or CSF testing as appropriate. The autologous cellular product will be manufactured using the CliniMACS Prodigy device and patients will receive one of several escalating doses with close monitoring for toxicity and response. The trial is sponsored by Memorial Sloan Kettering Cancer Center in collaboration with Miltenyi Biomedicine and is conducted at MSK sites in New Jersey.

Who should consider this trial

Good fit: Adults (≥18) with relapsed or refractory primary or secondary CNS lymphoma of the DLBCL subtype who have had at least one prior methotrexate-based CNS-directed therapy and meet the imaging or CSF evidence requirements are ideal candidates.

Not a fit: Patients who do not meet the trial's inclusion criteria (for example, non-DLBCL histology, under 18, or lacking required imaging/CSF confirmation) or who cannot undergo leukapheresis or required site visits are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, MB-CART19.1 could provide a new targeted treatment option for patients whose CNS lymphoma has returned or not responded to prior therapies.

How similar studies have performed: CD19-directed CAR T-cell therapies have transformed treatment for systemic DLBCL and early reports suggest some promise in CNS lymphoma, but dedicated CNS-directed CAR-T approaches are still early and under evaluation.

Eligibility criteria

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.
* Patients with HIV
* Patients with active hepatitis B or hepatitis C infection (as manifested by either detectable hepatitis B virus DNA by PCR, hepatitis virus C RNA by PCR, or positivity for hepatitis B surface or core antigen)
* Patients with uncontrolled systemic fungal, bacterial, viral or other infection at time of leukapheresis or at time of CAR T cell infusion
* Patients with any concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation or hormonal therapy, with the exception of squamous and basal cell carcinoma of skin
* Patients exposed to immune checkpoint inhibitor within 8 weeks
* Use of herbal supplements are not allowed on study
* Any other issue which, in the opinion of the treating physician or PI, would make the patient ineligible for the study.

Where this trial is running

Basking Ridge, New Jersey and 6 other locations

• Memorial Sloan Kettering at Basking Ridge (All Protocol Activities) — Basking Ridge, New Jersey, United States (RECRUITING)
• Memorial Sloan Kettering at Monmouth (Limited Protocol Activities) — Middletown, New Jersey, United States (RECRUITING)
• Memorial Sloan Kettering at Bergen (Limited Protocol Activities) — Montvale, New Jersey, United States (RECRUITING)
• Memorial Sloan Kettering at Suffolk-Commack (Limited Protocol Activities) — Commack, New York, United States (RECRUITING)
• Memorial Sloan Kettering at Westchester (Limited Protocol Activities) — Harrison, New York, United States (RECRUITING)
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York, New York, United States (RECRUITING)
• Memorial Sloan Kettering at Nassau (Limited Protocol Activities) — Uniondale, New York, United States (RECRUITING)

Study contacts

• Principal investigator: Ivan Kotchetkov, MD — Memorial Sloan Kettering Cancer Center
• Study coordinator: Ivan Kotchetkov, MD

Conditions: Primary Central Nervous System Lymphoma, Secondary Central Nervous System Lymphoma, MB-CART19.1 Cellular Therapy, Relapsed/Refractory, CliniMACS Prodigy Device