Tafasitamab Plus Lenalidomide in Relapsed CNS Lymphoma

NCT05351593 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 212531NCI-2022-03704
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (4)

• 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.

  Up to 1 cycle (1 cycle is equal to 28 days)

• 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.

  Up to 1 cycle (1 cycle is equal to 28 days)

• 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

  Up to 1 cycle (1 cycle is equal to 28 days)

• 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).

  Up to 3 months

Secondary Outcomes (3)

• Proportion of participants with Treatment-Related Adverse Events

  Up to 90 days

• Median Progression-free survival (PFS) (Phase 2)

  Up to 1 year

• Median Overall Survival (OS)

  Up to 1 year

Study Arms (2)

Phase 1 (Tafasitamab, Lenalidomide)

EXPERIMENTAL

Participants will be given 12mg of Tafasitamab on days 1, 4, 8, 15, and 22 of cycle 1, days 1, 8, 15, and 22 of cycles 2 \& 3, and days 1 and 15 for any cycle thereafter. Participants will also be given daily Lenalidomide on days 1-21 of each cycle.

Drug: Tafasitamab; Drug: Lenalidomide

Phase 2 (Tafasitamab, Lenalidomide)

EXPERIMENTAL

Participants will be given 12mg of Tafasitamab on days 1, 4, 8, 15, and 22 of cycle 1, days 1, 8, 15, and 22 of cycles 2 \& 3, and days 1 and 15 for any cycle thereafter. Participants will also be given daily Lenalidomide on days 1-21 of each cycle at the recommended phase 2 dose.

Drug: Tafasitamab; Drug: Lenalidomide

Interventions

Tafasitamab DRUG

Given IV

Also known as: MOR208

Phase 1 (Tafasitamab, Lenalidomide); Phase 2 (Tafasitamab, Lenalidomide)

Lenalidomide DRUG

Given Orally

Also known as: Revlimid

Phase 1 (Tafasitamab, Lenalidomide); Phase 2 (Tafasitamab, 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 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.
• Anticipated survival \> 2 months, as determined by the investigator.
• Eastern Cooperative Oncology Group (ECOG) performance status \<=1 (Karnofsky performance status \>= 70%)
• Demonstrates adequate organ function as defined below:
• Absolute neutrophil count (ANC) ≥ 1.5 X 10\^9/ L (1,500/ microliter (mcL), growth factors permitted).
• Platelets \>= 50 X 10\^9 / L (50,000/ mcL, platelet transfusion independent).
• Total bilirubin \<= 1.5 x institutional upper limit of normal,unless elevated due to Gilbert's syndrome.
• Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) \<=3 X institutional upper limit of normal.
• Alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) \<=3 X institutional upper limit of normal.
• d. Creatinine clearance (CrCl, calculated) \>= 60 mL/min/1.73 m\^2, calculated using the Cockcroft-Gault equation. CrCl \> 60 mL/min/1.73 m2 is requisite for eligibility for the phase I dose-escalation phase of the study.
• Ability to understand and the willingness to sign a written informed consent document.
• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. If a HBV test comes up positive due to Intravenous immunoglobulin (IVIG) and the participant has no prior history of HBV, then perform a HBV PCR to confirm.

You may not qualify if:

• 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.
• Has a history of HIV infection.
• Has CNS post-transplant lymphoproliferative disease (PTLD).
• Has known hypersensitivity to lenalidomide or Tafasitamab.
• Pregnant women and women of child-bearing potential who will not using an effective method of birth control (detailed in Appendix 3) are excluded from this study because the study drugs have potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lenalidomide and/or Tafasitamab, breastfeeding should be discontinued if the mother is treated with study drugs.
• Has any significant medical condition or comorbidity that could compromise patient safety (e.g., uncontrolled serious infection).

Sponsors & Collaborators

• James Rubenstein: lead
• Incyte Corporation: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

MeSH Terms

Interventions

tafasitamab; Lenalidomide

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

Study Officials

• James Rubenstein, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hayley Wallace

CONTACT

877-827-3222; Hayley.Wallace@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 22, 2022
• First Posted: April 28, 2022
• Study Start: June 8, 2022
• Primary Completion: September 30, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: February 3, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)