This is a single arm open-label multicenter phase I/II investigation of combination lenalidomide/Tafasitamab in patients with relapsed central nervous system (CNS) lymphoma. This is the first study to examine a naked anti-CD19 monoclonal antibody in relapsed CNS lymphoma patients as well as the combination of anti-CD19 antibody plus an Immunomodulatory imide drugs (IMiDs) in CNS lymphomas. This study will also test the novel hypothesis that Tafasitamab enhances blood-brain barrier permeability, a potential property that could have broad clinical implications.
Participants must have relapsed primary or secondary CNS lymphoma, diffuse large B-cell lymphoma (DLBCL) type, based on radiographic, ophthalmologic, or CSF criteria (evidence of malignant cells based on CSF studies: cytospin/cytology and flow-cytometry).
Concomitant systemic lymphoma as well as transformation from follicular lymphoma and/or Chronic lymphocytic leukemia (CLL) to an aggressive B-cell histology is allowed.
Participants are eligible with disease in each CNS compartment: brain, leptomeninges/CSF and intraocular compartment.
Age >= 18 years.
Has received systemic anti-cancer therapies within 2 weeks of first dose, radiation within 1 week, antibody therapy within 4 weeks.
Has not recovered from adverse events due to prior anti-cancer therapy to ≤ grade 1 or baseline (other than alopecia).
Is currently receiving any other investigational agents.
Has participated in a study of an investigational product and received study treatment or used an investigational device within four weeks of the first dose of treatment.
Parallel
Tafasitamab
DrugGiven IV
Lenalidomide
DrugGiven Orally
Proportion of participants with dose limiting toxicities (DLTs) (Phase 1)
Toxicities will be classified using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The DLT will be based on the tolerability observed during the first cycle. In order for a patient to be assessed for DLT, they must receive at least 75% of lenalidomide dose (16 of the planned 21 days of lenalidomide administration). The maximum tolerated dose of lenalidomide/Tafasitamab will be the highest dose at which fewer than one-third of patients experience dose limiting toxicity. If multiple toxicities are seen, the presence of dose limiting toxicity should be based on the most severe toxicity experienced.
Maximum Tolerated Dose (MTD) (Phase 1)
The MTD is the highest dose at which no more than one instance of a DLT is observed among 6 participants treated.
Recommended Phase 2 Dose (RP2D) (Phase1)
The RP2D is the dose at which the Phase 2 portion of the study will begin enrolling. RP2D will be determined based on all data including available pharmacokinetics (PK), pharmacodynamic (PD), target engagement, efficacy, safety and tolerability data collected during Phase 1
Percentage of participants with demonstrated Clinical Benefit Rate (CBR) (Phase 2)
Response to the combination lenalidomide/Tafasitamab treatment is defined as achieving clinical benefit better at three months restaging. That is overall tumor shrinkage within three months of treatment initiation or stable disease at three months restaging. Response criteria will be graded using the Cytologic Response Criteria, Neurologic Response Criteria, and Radiographic Response Criteria developed by the International Workshop to Standardize Baseline Evaluation and Response Criteria in Primary CNS Lymphoma The response rate is defined as the proportion of study participants meeting the definition of response in Efficacy Analysis Set (EAS). Response rate will be summarized by percentage, along with the corresponding exact 95% confidence intervals (CIs).
Proportion of participants with Treatment-Related Adverse Events
Serious adverse events, adverse events which are \>=Grade 3, and adverse events resulting in discontinuation of treatment, withdrawal from the study, and deaths on-study will be used to determine the proportion of participants with treatment-related adverse events. Analyses will be performed based on the safety population.
Median Progression-free survival (PFS) (Phase 2)
PFS is defined as the duration from first dose to disease relapse, progression, or death, whichever occurs first. The censoring time for PFS is set to be last study assessment for progression, and will be descriptively analyzed using Kaplan-Meier methods
Median Overall Survival (OS)
OS is defined as the duration from first dose to death. The censoring time for OS is set to be the last study contact. OS will be descriptively analyzed using Kaplan-Meier methods.
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James Rubenstein
Lead sponsor
University of California, San Francisco
Sponsor institution
Incyte Corporation
Collaborator
