Newly-diagnosed high-intermediate and high-risk diffuse large B-cell lymphoma (DLBCL). MedDRA version: 21.0 Level: PT Classification code 10012818 Term: Diffuse large B-cell lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classification code 10012820 Term: Diffuse large B-cell lymphoma NOS System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Monjuvi
Product Name: Tafasitamab
Product Code: MOR00208
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Tafasitamab
Other descriptive name: MOR0
Sponsors
MorphoSys AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent. 2. Age 18 to 80 years at time of signing of the ICF. 3. Previously untreated patients with local biopsy-proven, CD20-positive DLBCL, including one of the following diagnoses by 2016 World Health Organization (WHO) classification of lymphoid neoplasms are eligible: a. DLBCL, NOS including GCB type, ABC type b. T-cell rich large BCL c. Epstein-Barr virus-positive DLBCL, NOS d. Anaplastic lymphoma kinase (ALK)-positive large BCL e. Human herpes virus-8 (HHV8)-positive DLBCL, NOS f. High-grade BCL with MYC and B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) rearrangements (double-hit or triple-hit lymphoma). g. DLBCL coexistent with either follicular lymphoma (FL) of any grade, gastric MALT lymphoma or non-gastric MALT lymphoma h. FL grade 3b 4. Availability of archival or freshly collected tumor tissue sent for retrospective central pathology review. 5. Up to six of the largest target nodes, nodal masses, or other lymphomatous lesions that are measurable in two diameters should be identified by local assessment from different body regions representative of the patient’s overall disease burden and include mediastinal and retroperitoneal disease, if involved. 6. ECOG performance status of 0, 1, or 2. 7. IPI status of 3 to 5 (for patients > 60 years of age) or aaIPI 2 to 3 (for patients = 60 years of age). 8. Diagnosis to treatment interval, defined as the time between the date of DLBCL diagnosis (date of the first biopsy specimen containing lymphoma according to the local pathology report) and the start of treatment (C1D1) = 28 days. 9. Left ventricular ejection fraction equal to or greater than lower limit of institutional normal range, assessed by local echocardiography or cardiac multi-gated acquisition (MUGA) scan 10. Patient must have the following local laboratory criteria at screening: a. Absolute neutrophil count (ANC) = 1.5 x 109/L (unless secondary to bone marrow involvement by DLBCL) b. Platelet count = 75 x 109/L (unless secondary to bone marrow involvement by DLBCL) c. Total serum bilirubin < 1.5 × upper limit of normal (ULN) unless secondary to Gilbert’s Syndrome or documented liver involvement by lymphoma. Patients with Gilbert’s Syndrome or documented liver involvement by lymphoma may be included if their total bilirubin is = 5 × ULN d. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) = 3 × ULN, or = 5 × ULN in cases of documented liver involvement e. Serum creatinine clearance must be = 30 mL/minute either measured or calculated using a standard Cockcroft and Gault formula (Cockroft and Gault, 1976) 11. In the opinion of investigator, the patient must: a. Be able and willing to receive adequate prophylaxis and/or therapy for thromboembolic events, e.g. aspirin 70 to 325 mg daily or low molecular weight heparin. b. Be able to understand, give written informed consent, and comply with all study-related procedures, medication use, and evaluations c. Not have a history of noncompliance in relation to medical regimens nor be considered potentially unreliable and/or uncooperative d. Be able to understand the reason for complying with the special conditions of the pregnancy prevention risk management plan and in writing acknowledge to adhere to this plan 12. Due to the teratogenic potential of lenalidomide, females of childbearing potential (FCBP) must: a. Not be pregnant as confirmed by a neg
Exclusion criteria
Exclusion criteria: 1. Any other histological type of lymphoma according to WHO 2016 classification of lymphoid neoplasms, e.g., primary mediastinal (thymic) large B-cell lymphoma, Burkitt’s lymphoma, BCL, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma (grey-zone lymphoma); primary effusion lymphoma; primary cutaneous DLBCL, leg type; primary DLBCL of the CNS; DLBCL arising from CLL or indolent lymphoma. 2. History of radiation therapy to = 25% of the bone marrow for other diseases. 3. History of prior non-hematologic malignancy except for the following: a. Malignancy treated with curative intent and with no evidence of active disease present for more than 2 years before screening b. Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer c. Adequately treated carcinoma in situ without current evidence of disease 4. Patients with: a. Positive local test result during screening for hepatitis C (hepatitis C virus [HCV] antibody serology testing) and a positive test for HCV RNA. Patients with positive serology must have been tested locally for HCV RNA and are eligible, in case of negative HCV RNA test results b. Positive local test result during screening for chronic hepatitis B virus (HBV) infection (defined by hepatitis B surface antigen [HBsAg] positivity). Patients with occult or prior HBV infection (defined as negative HBsAg and positive total hepatitis B core antibody [HBcAb]) may be included if HBV DNA is undetectable (local test result), provided that they are willing to undergo ongoing DNA testing. Antiviral prophylaxis may be administered as per institutional guidelines. Patients who have protective titers of hepatitis B surface antibody (HBsAb) after vaccination or prior but cured hepatitis B are eligible c. Seropositive (local test result during screening) for, or history of active viral infection with human immunodeficiency virus (HIV) d. Known active systemic bacterial, viral, fungal, or other infection at screening, including patients with suspected active or latent tuberculosis (as confirmed by a positive interferon-gamma release assay) e. Positive results for the human T-lymphotrophic 1 virus (HTLV-1). HTLV testing during screening is required for patients at sites in endemic countries (Japan and Melanesia and countries in the Caribbean basin, South America, Central America, and sub-Saharan Africa) f. Known CNS lymphoma involvement g. History or evidence of clinically significant cardiovascular, CNS and/or other systemic disease that in the investigator’s opinion would preclude participation in the study or compromise the patient’s ability to give informed consent h. History or evidence of rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption i. Vaccination with live vaccine within 21 days prior to study randomization j. Major surgery within up to 21 days prior to signing the informed consent form (ICF), unless the patient is recovered at the time of signing the ICF k. Any systemic anti-lymphoma and/or investigational therapy prior to the start of C1D1, except for permitted pre-phase treatment l. Contraindication to any of the individual components of R-CHOP, including prior receipt of anthracyclines m. Pregnancy or lactation n. History of hypersensitivity to any component of R-CHOP, to lenalidomide, to compounds of similar biological or chem
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of tafasitamab plus lenalidomide in addition to R-CHOP versus tafasitamab placebo, lenalidomide placebo and R-CHOP (henceforth referred to as R-CHOP in the context of the control arm).;Secondary Objective: 1. To compare the efficacy (additional parameters) of tafasitamab plus lenalidomide in addition to R-CHOP versus R-CHOP. 2. To compare the safety of tafasitamab plus lenalidomide in addition to R-CHOP versus R-CHOP. 3. To compare the efficacy of tafasitamab plus lenalidomide in addition to R-CHOP versus R-CHOP in DLBCL subtypes of COO 4. To compare the efficacy of tafasitamab plus lenalidomide in addition to R-CHOP versus R-CHOP in DLBCL subtypes: DLBCL not otherwise specified versus HGBL versus other. 5. To compare the incidence of central nervous system relapse in patients receiving tafasitamab plus lenalidomide in addition to R-CHOP versus R-CHOP. 6. To assess patient-reported outcomes in patients receiving tafasitamab plus lenalidomide in addition to R-CHOP versus R-CHOP. 7. To assess the pharmacokinetic profile of tafasitamab. 8. To assess the potential immunogenicity of tafasitamab. 9. To assess the role of baseline NK cell count as a predictor of response. ;Primary end point(s): PFS, defined as the time from randomization to the first occurrence of disease progression or relapse as assessed by the investigator, using the Lugano Response Criteria for Malignant Lymphoma, or death from any cause, whichever occurs earlier.;Timepoint(s) of evaluation of this end point: Day 18 cycle 3 and EOT | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary 1. Event-free survival (EFS) as assessed by the investigator 2. Overall survival (OS) Secondary 1. Metabolic, PET-negative complete response (CR) rate at end of treatment (EOT) as assessed by the BIRC 2. Metabolic, PET-negative CR rate at EOT as assessed by the investigator 3. ORR at EOT as assessed by the investigator 4. Time to next anti-lymphoma treatment (TTNT) 5. Duration of CR as assessed by the investigator 6. Minimal residual disease (MRD) status by cell-free circulating tumor DNA (ctDNA) assessment at EOT 7. EFS rate at 3 years as assessed by the investigator 8. PFS rate at 3 years as assessed by the investigator 9. OS rate at 3 years 10. Incidence and severity of TEAEs from the first dose of study medication until 30 days after Day 21 of the last treatment cycle. 11. PFS as assessed by the investigator by COO subtype 12. Investigator-assessed EFS by COO subtype 13. OS by COO subtype 14. Metabolic, PET-negative CR rate at EOT as assessed by the BIRC by COO subtype 15. Metabolic, PET-negative CR rate at EOT as assessed by the investigator by COO subtype 16. PFS as assessed by the investigator by locally determined histological subtype 17. Investigator assessed EFS by locally determined histological subtype 18. OS by locally determined histological subtype 19. Metabolic, PET-negative CR rate at EOT as assessed by the BIRC by locally determined histological subtype 20. Metabolic, PET-negative CR rate at EOT as assessed by the investigator by locally determined histological subtype 21. 2-year rate of relapse with CNS involvement, as assessed by the investigator 22. Health-related quality of life (HRQoL), using the European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 and Functional Assessment of Cancer Therapy for Patients with Lymphoma (FACT-Lym) standardized measures. 23. Serum concentration of tafasitamab at specific time points (trough and Cmax levels). 24. Incidence o | — |
Countries
Argentina, Australia, Austria, Canada, Colombia, Czechia, Czech Republic, France, Germany, Hungary, India, Ireland, Israel, Italy, Korea, Republic of, Malaysia, New Zealand, Philippines, Poland, Romania, Russian Federation, Serbia, Slovakia, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactGlobal Program Medical Director
MorphoSys AG
Outcome results
None listed