Ibrutinib With Rituximab and Lenalidomide for Patients With Recurrent/Refractory Primary or Secondary Central Nervous System Lymphoma (PCNSL/SCNSL)

NCT03703167 | Completed Phase 1 FDA Drug

• 1 other identifier: 18-432
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 7

Brief Summary

The investigator's want to find out if treatment with ibrutinib, rituximab, and lenalidomide are safe and better than the usual approach in patients with recurrent or refractory central nervous system lymphoma.

Conditions

Primary Central Nervous System Lymphoma (PCNSL); Secondary Central Nervous System Lymphoma (SCNSL)

Keywords

Ibrutinib; Rituximab; Lenalidomide; relapsed/refractory PCNSL; relapsed/refractory SCNSL; 18-432

Outcome Measures

Primary Outcomes (1)

• maximum tolerated dose (MTD) of ibrutinib

  A standard 3+3 design will be employed. Four dose levels will be investigated. Patients will be treated in cohorts of size three to six and the dosage will be escalated if the clinical toxicity is acceptable. A dose limiting toxicity (DLT) is defined as in any of the following during cycle 1: any grade 4 hematologic toxicity, grade 3 febrile neutropenia and grade 3 thrombocytopenia associated with bleeding or any grade ≥3 non-hematologic toxicity that does not respond to supportive therapy and at least possibly related to treatment with ibrutinib. A minimum of 4 up to a maximum of 30 patients will be enrolled.

  1 year

Secondary Outcomes (1)

• progression free survival

  2 years

Study Arms (1)

ibrutinib in combination with rituximab and lenalidomide

EXPERIMENTAL

Ibrutinib will be given day 1-28; Lenalidomide will be given day 1-21; Rituximab will be given on day 1. Rituximab is given for 6 cycles; Lenalidomide is given for 12 cycles; Ibrutinib is continued until disease progression, intolerable toxicity or death.

Drug: Ibrutinib; Drug: Lenalidomide; Drug: Rituximab

Interventions

Ibrutinib DRUG

Oral ibrutinib will be given between days 1 and 28 of each 28-day cycle and will be continued daily after completion of rituximab and lenalidomide. The starting dose of ibrutinib is 560 mg/day (dose level 1) and (dose level 2 ibrutinib: 840 mg daily).

ibrutinib in combination with rituximab and lenalidomide

Lenalidomide DRUG

Oral lenalidomide will be given between days 1 and 21 of each 28-day cycle for a maximum of 12 cycles. The starting dose of lenalidomide is 10 mg/day (dose level 1 \& 2) lenalidomide: 15 mg daily (dose level 3) and lenalidomide: 20 mg daily (dose level 4).

ibrutinib in combination with rituximab and lenalidomide

Rituximab DRUG

Intravenous rituximab (500mg/m2) will be given on day 1 of all cycles (+/- 3 days), for up to 6 cycles.

ibrutinib in combination with rituximab and lenalidomide

Eligibility Criteria

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

You may qualify if:

• Participants must be able to understand and be willing to sign a written informed consent document.
• Men and woman who are at least 18 years of age on the day of consenting to the study.
• Histologically documented PCNSL or histologically documented systemic diffuse large B-cell lymphoma (DLBCL).
• Patients must have relapsed/refractory PCNSL or relapsed/refractory SCNSL
• All patients need to have received at least one prior CNS directed therapy. There is no restriction on the number of recurrences.
• Patients with parenchymal lesions must have unequivocal evidence of disease progression on imaging (MRI of the brain or head CT) 21 days prior to study registration. For patients with leptomeningeal disease only, CSF cytology must document lymphoma cells and/or imaging findings consistent with CSF disease 21 days prior to study registration (at the discretion of the investigator).
• Participants must have an ECOG performance status of 0, 1, or 2.
• Participants must have adequate bone marrow and organ function shown by:
• Absolute neutrophil count (ANC) ≥ 1.0 x 10\^9/L
• Platelets ≥ 75 x 10\^9/L and no platelet transfusion within the past 21 days prior to study registration
• Hemoglobin (Hgb) ≥ 8 g/dL and no red blood cell (RBC) transfusion within the past 21 days prior to study registration
• International Normalized Ratio (INR) ≤ 1.5 and PTT (aPTT) ≤ 1.5 times the upper limit of normal
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the upper limit of normal
• Serum bilirubin ≤ 1.5 times the upper limit of normal; or total bilirubin ≤ 3 times the upper limit of normal with direct bilirubin within the normal range in patients with well documented Gilbert Syndrome.
• Serum creatinine ≤ 2 times the upper limit of normal

You may not qualify if:

• Patients with SCNSL actively receiving treatment for extra-CNS disease are excluded.
• Patient is concurrently using other approved or investigational antineoplastic agents.
• 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 prior to starting the study drug, or the patient has not recovered from the side effects of such therapy.
• Patient has received external beam radiation therapy to the CNS within 21 days of the first dose of the study drug.
• Patient requires more than 8 mg of dexamethasone daily or the equivalent
• Patient has an active concurrent malignancy requiring active therapy
• The patient has been treated with radio- or toxin-immunoconjugates within 70 days of the first dose of the study drug.
• Patient is allergic to components of the study drug.
• Patient is using warfarin or any other Coumadin-derivative anticoagulant or vitamin K antagonists. Patients must be off warfarin-derivative anticoagulants for at least seven days prior to starting the study drug. Low molecular weight heparin is allowed. Patients with congenital bleeding diathesis are excluded.
• Patient is taking a drug known to be a moderate and strong inhibitor or inducers of the P450 isoenzyme CYP3A. Participants must be off P450/CYP3A inhibitors and inducers for at least two weeks prior to starting the study drug.
• Patient is using systemic immunosuppressant therapy, including cyclosporine A, tacrolimus, sirolimus, and other such medications, or chronic administration of \> 5 mg/day or prednisone or the equivalent. Participants must be off immunosuppressant therapy for at least 28 days prior to the first dose of the study drug.
• Patient has significant abnormalities on screening electrocardiogram (EKG) and active and significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, hypertension, valvular disease, pericarditis, or myocardial infarction within 6 months of screening,
• Patient has a known bleeding diathesis (e.g. von Willebrand"s disease) or hemophilia.
• Patient is known to have human immunodeficiency virus (HIV) infection.
• Patient is known to have a history of active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) as determined by serologic tests.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Pharmacyclics LLC.: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Publications (1)

• Schaff LR, Piotrowski AF, Pentsova E, Gavrilovic IT, Lin A, Kaley TJ, Wongchai V, Emadi-Paramkouhi L, Madzsar J, Quinn L, Gonzalez A, Breakey L, Tang SS, Mendez JS, Malani R, Nolan C, Hatzoglou V, Young RJ, DeAngelis LM, Reiner AS, Panageas KS, Francis JH, Mellinghoff IK, Grommes C. Phase Ib study with expansion of ibrutinib, lenalidomide, and rituximab in patients with relapsed/refractory central nervous system lymphoma. Neuro Oncol. 2025 Sep 17;27(8):2107-2116. doi: 10.1093/neuonc/noaf104.

  PMID: 40269592 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Recurrence

Interventions

ibrutinib; Lenalidomide; Rituximab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Christian Grommes, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

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: This is an open-label, phase Ib trial with dose expansion of the BTK inhibitor ibrutinib in combination with rituximab and lenalidomide.

Study Record Dates

• First Submitted: October 9, 2018
• First Posted: October 11, 2018
• Study Start: January 22, 2019
• Primary Completion: January 26, 2026
• Study Completion: January 26, 2026
• Last Updated: January 29, 2026

Record last verified: 2026-01

Locations

US (7)