Safety and Pharmacokinetics Study of a Modified Tafasitamab IV Dosing Regimen Combined With Lenalidomide in R-R DLBCL Patients

Study Overview
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Brief Summary
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This is an open-label, multicentre study too Evaluate the Safety and Pharmacokinetics of a Modified Tafasitamab IV Dosing Regimen Combined with Lenalidomide (LEN) in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL) who have had at least one, but no more than three prior systemic regimens and who are not eligible for high dose chemotherapy (HDC) with autologous stem-cell transplantation (ASCT) at the time of study entry.

Official Title
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A Phase 1b/2, Open-Label, Multicenter Study to Evaluate the Safety and Pharmacokinetics of a Modified Tafasitamab IV Dosing Regimen Combined With Lenalidomide in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Conditions
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Diffuse Large B Cell Lymphoma

Intervention / Treatment
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* Drug: Tafasitamab
* Drug: Lenalidomide


Participation Criteria
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Eligibility Criteria
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Major Inclusion Criteria: Capable of giving signed informed consent Age 18 years or older Histologically confirmed diagnosis of DLBCL Tumor tissue for retrospective central pathology review must be provided as an adjunct to participation in this study. Patients must have: relapsed and/or refractory disease at least one bidimensionally measurable, PET positive disease site (transverse diameter of ≥1.5 cm and perpendicular diameter of ≥1.0 cm at baseline) received at least one, but no more than three previous systemic regimens for the treatment of DLBCL and one therapy line must have included a CD20-targeted therapy Eastern Cooperative Oncology Group 0 to 2 Patients not considered in the opinion of the investigator eligible to undergo intensive salvage therapy including ASCT Patients must meet the following laboratory criteria at screening: absolute neutrophil count ≥1.5 × 10^9/L platelet count ≥90 × 10^9/L total serum bilirubin ≤2.5 × ULN or ≤5 × ULN in cases of Glibert's Syndrome or liver involvement by lymphoma alanine transaminase, aspartate aminotransferase and alkaline phosphatase ≤3 × ULN or <5 × ULN in cases of liver involvement serum creatinine clearance ≥ 60 mL/minute Patients who received previous CD19 targeted therapy (other than tafasitamab) must have CD19 positive lymphoma confirmed on a biopsy taken since completing the prior CD19 targeted therapy Patients with primary refractory disease who received at least one, but no more than three previous systemic regimens (including a CD20 targeted therapy) Major Exclusion Criteria: Patients who are legally institutionalized or concurrent enrollment in another interventional clinical study Patients who have: other histological type of lymphoma a history of double/triple hit genetics Patients who have, within 14 days prior to Day 1 dosing: not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy or other lymphoma specific therapy undergone major surgery (with 4 weeks) or suffered from significant traumatic injury received live vaccines (within 4 weeks). required parenteral antimicrobial therapy for active, intercurrent infections Patients who: have not recovered sufficiently from the adverse toxic effects of prior therapies were previously treated with IMiDs® (e.g. thalidomide, LEN) have history of hyper sensitivity to compounds of similar biological or chemical composition to tafasitamab IMiDs® and/or the excipients contained in the study treatment formulations have undergone ASCT within the period ≤ 3 months prior to signing the informed consent form. have undergone previous allogenic stem cell transplantation have a history of deep venous thrombosis/embolism and who are not willing/able to take venous thromboembolic event prophylaxis during the entire treatment period concurrently use other anticancer or experimental treatments History of other malignancy that could affect compliance with the protocol or interpretation of results. Exceptions Patients with any malignancy appropriately treated with curative intent and the malignancy has been in remission without treatment for >2 years prior to enrollment are eligible Patients with low-grade, early-stage prostate cancer (Gleason score 6 or below, Stage 1 or 2) with no requirement for therapy at any time prior to study are eligible Patients with: positive hepatitis B and/or C serology. known seropositivity for or history of active viral infection with human immunodeficiency virus (HIV) CNS lymphoma involvement history or evidence of clinically significant cardiovascular, CNS and/or other systemic disease that would in the investigator's opinion preclude participation in the study or compromise the patient's ability to give informed consent history or evidence of rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption gastrointestinal (GI) abnormalities (issue with absorption) including the inability to take oral medication history or evidence of severe hepatic impairment (total serum bilirubin > 3mg/dL), jaundice unless secondary to Gilbert's syndrome or documented liver involvement by lymphoma history of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical class any other medical condition which, in the investigator's opinion, makes the patient unsuitable for the study Female participants: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods and refrain from breast feeding and donating eggs; agreement to ongoing pregnancy testing during the course of the study, and after study therapy has ended Male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom and agreement to refrain from donating sperm

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (Tafasitamab + Lenalidomide)<br>Treatment: Tafasitamab will be combined with lenalidomide in R/R DLBCL patients. Dose: Cohort 1: The dose of tafasitamab will be level 1 high dose in combination with the approved dose Cohort 2: The dose of tafasitamab will be level 2 high dose in combination with the approved dose Expansion Cohort: The dose of tafasitamab will be the dose that is deemed safe and tolerable as determined from cohort 1 & cohort 2 Treatment consisting of tafasitamab and lenalidomide combination will be administered until disease progression, unacceptable toxicity, or discontinuation for any other reason, whichever comes first. Lenalidomide can be given for up to 12 cycles in total, after which patients can continue with tafasitamab as monotherapy until progression or unacceptable toxicity. | Drug: Tafasitamab<br>* tafasitamab will be administered intravenously at protocol defined timepoints<br>* Other names: Xmab5574;Drug: Lenalidomide<br>* lenalidomide will be administered orally at protocol defined timepoints<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate safety and tolerability | Incidence and severity of TEAEs | 1 - 3 years approximately | 
| Determine recommended dose | Incidence and severity of TEAEs combination with lenalidomide in R/R DLBCL patients | 1 - 3 years approximately | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate pharmacokinetic profile | Tafasitamab serum concentration (Ctrough) | Upto 1 year | 
| Evaluate pharmacokinetic profile | Tafasitamab serum concentration (Cmax) | Upto 3 months | 
| Assess anti-tumor activity | Number of participants with Best Objective Response Rate, ORR = complete response [CR] + partial response [PR]; by Investigator assessment based on Cheson et al (2007) | upto 1 year | 
| Duration of response (DoR) | Investigator assessment | 1 - 3 years approximatey | 
| Progression-free Survival (PFS) | Investigator assessment | 1 - 3 years approximately | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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monoclonal antibody, CD19, tafasitamab