Clinical Trials /

Tafasitamab + Lenalidomide + R-CHOP Versus R-CHOP in Newly Diagnosed High-intermediate and High Risk DLBCL Patients

NCT04824092

Description:

This is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial designed to compare the efficacy and safety of the humanized monoclonal anti CD19 antibody tafasitamab plus lenalidomide in addition to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) versus R-CHOP in previously untreated, high-intermediate and high-risk patients with newly-diagnosed DLBCL

Related Conditions:
  • ALK-Positive Large B-Cell Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • Grade 3b Follicular Lymphoma
  • HHV8-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • High Grade B-Cell Lymphoma with MYC and BCL2 and/or BCL6 Rearrangements
  • T-Cell/Histiocyte-Rich Large B-Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Tafasitamab + Lenalidomide + R-CHOP Versus R-CHOP in Newly Diagnosed High-intermediate and High Risk DLBCL Patients
  • Official Title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial Comparing the Efficacy and Safety of Tafasitamab Plus Lenalidomide in Addition to R-CHOP Versus R-CHOP in Previously Untreated, High-intermediate and High-risk Patients With Newly-diagnosed Diffuse Large B-cell Lymphoma (DLBCL)

Clinical Trial IDs

  • ORG STUDY ID: MOR208C310
  • NCT ID: NCT04824092

Conditions

  • Diffuse Large B-cell Lymphoma

Interventions

DrugSynonymsArms
TafasitamabMonjuviTafasitamab plus lenalidomide in addition to R-CHOP
LenalidomideTafasitamab plus lenalidomide in addition to R-CHOP
RituximabTafasitamab placebo plus lenalidomide placebo in addition to R-CHOP
CyclophosphamideTafasitamab placebo plus lenalidomide placebo in addition to R-CHOP
DoxorubicinTafasitamab placebo plus lenalidomide placebo in addition to R-CHOP
VincristineTafasitamab placebo plus lenalidomide placebo in addition to R-CHOP
PrednisoneTafasitamab placebo plus lenalidomide placebo in addition to R-CHOP
Tafasitamab placeboTafasitamab placebo plus lenalidomide placebo in addition to R-CHOP
Lenalidomide placeboTafasitamab placebo plus lenalidomide placebo in addition to R-CHOP

Purpose

This is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial designed to compare the efficacy and safety of the humanized monoclonal anti CD19 antibody tafasitamab plus lenalidomide in addition to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) versus R-CHOP in previously untreated, high-intermediate and high-risk patients with newly-diagnosed DLBCL

Trial Arms

NameTypeDescriptionInterventions
Tafasitamab plus lenalidomide in addition to R-CHOPExperimentalPatients will receive tafasitamab plus lenalidomide in addition to R-CHOP for six 21-day cycles: Tafasitamab dose: 12 mg/kg body weight. Each 21-day cycle (cycles 1-6) will comprise of a tafasitamab IV infusion on Day 1, Day 8 and Day 15. Lenalidomide dose: 25 mg as a starting dose per os (orally) once per day on Days 1-10 of each 21-day cycle R-CHOP dose: Rituximab (or locally approved biosimilar) 375 mg/m2, IV Day 1 of every 21-day cycle; Cyclophosphamide 750 mg/m2, IV Day 1 of 21-day cycle; Doxorubicin 50 mg/m2, IV Day 1 of 21-day cycle; Vincristine 1.4 mg/m2 (max 2 mg) IV Day 1 of 21-day cycle; Prednisone/prednisolone 100 mg/day, per os, Day 1-5 of every 21-day cycle
  • Tafasitamab
  • Lenalidomide
  • Rituximab
  • Cyclophosphamide
  • Doxorubicin
  • Vincristine
  • Prednisone
Tafasitamab placebo plus lenalidomide placebo in addition to R-CHOPPlacebo ComparatorPatients will receive tafasitamab placebo plus lenalidomide placebo in addition to R-CHOP for six 21-day cycles: Tafasitamab placebo: 0.9% saline solution Days 1, 8 and 15 of each 21-day cycle Lenalidomide placebo: Days 1-10 of each 21-day cycle R-CHOP dose: Rituximab (or locally approved biosimilar) 375 mg/m2, IV Day 1 of every 21-day cycle; Cyclophosphamide 750 mg/m2, IV Day 1 of 21-day cycle; Doxorubicin 50 mg/m2, IV Day 1 of 21-day cycle; Vincristine 1.4 mg/m2 (max 2 mg) IV Day 1 of 21-day cycle; Prednisone/prednisolone 100 mg/day, per os, Day 1-5 of every 21-day cycle
  • Rituximab
  • Cyclophosphamide
  • Doxorubicin
  • Vincristine
  • Prednisone
  • Tafasitamab placebo
  • Lenalidomide placebo

Eligibility Criteria

        Major Inclusion Criteria:

          -  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:

               1. DLBCL, NOS including GCB type, ABC type

               2. T-cell rich large BCL

               3. Epstein-Barr virus-positive DLBCL, NOS

               4. Anaplastic lymphoma kinase (ALK)-positive large BCL

               5. Human herpes virus-8 (HHV8)-positive DLBCL, NOS

               6. 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). Please note: Patients
                  must be appropriate candidates for R-CHOP. If an investigator deems a patient
                  with a known double- or triple-hit lymphoma (HGBL) should be treated more
                  aggressively (e.g. dose-adjusted etoposide, prednisone, vincristine,
                  cyclophosphamide, doxorubicin and rituximab [DA-EPOCH-R] or cyclophosphamide,
                  vincristine, doxorubicin and dexamethasone (CVAD) followed by methotrexate and
                  cytarabine [Hyper CVAD]), this patient would not be considered eligible for this
                  study

               7. DLBCL coexistent with either follicular lymphoma (FL) of any grade, gastric MALT
                  lymphoma or non-gastric MALT lymphoma

               8. FL grade 3b

          -  Availability of archival or freshly collected tumor tissue sent for retrospective
             central pathology review

          -  IPI status of 3 to 5 (for patients > 60 years of age) or aaIPI 2 to 3 (for patients ≤
             60 years of age)

          -  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

          -  ECOG performance status of 0, 1, or 2

          -  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

          -  Adequate hematologic function

          -  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

        Major Exclusion Criteria:

          -  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

          -  History of prior non-hematologic malignancy except for the following:

               1. Malignancy treated with curative intent and with no evidence of active disease
                  present for more than 2 years before screening

               2. Adequately treated lentigo maligna melanoma without current evidence of disease
                  or adequately controlled non-melanomatous skin cancer

               3. Adequately treated carcinoma in situ without current evidence of disease

          -  Any systemic anti-lymphoma and/or investigational therapy prior to the start of C1D1,
             except for permitted pre-phase treatment

          -  Contraindication to any of the individual components of R-CHOP, including prior
             receipt of anthracyclines

          -  Known CNS lymphoma involvement

          -  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)

          -  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
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:PFS-INV
Time Frame:From randomization to the first occurrence of disease progression or relapse as assessed by the investigator, or death from any cause, whichever occurs earlier (up to 43 months)
Safety Issue:
Description:Progression-Free Survival as assessed by the investigator using the Lugano Response Criteria for Malignant Lymphoma

Secondary Outcome Measures

Measure:EFS-INV
Time Frame:From randomization until the first occurrence of disease progression or relapse as assessed by the INV using, start of new anti-lymphoma treatment or death from any cause, whichever occurs first (up to 43 months)
Safety Issue:
Description:Event-Free Survival as assessed by the investigator using the Lugano Response Criteria for Malignant Lymphoma
Measure:OS
Time Frame:From randomization until the date of death from any cause (up to 62 months)
Safety Issue:
Description:Overall Survival
Measure:Metabolic PET-negative CR-rate at EOT by BIRC
Time Frame:End of treatment, 4-8 weeks after last dose
Safety Issue:
Description:Metabolic PET-negative CR rate defined as the proportion of patients who achieved metabolic PET-negative CR as per Lugano 2014 criteria based on PET/CTs performed at the end of the treatment by BIRC
Measure:Metabolic PET-negative CR-rate at EOT by INV
Time Frame:End of treatment, 4-8 weeks after last dose
Safety Issue:
Description:Metabolic PET-negative CR rate defined as the proportion of patients who achieved metabolic PET-negative CR as per Lugano 2014 criteria based on PET/CTs performed at the end of the treatment by the investigator
Measure:MRD status at EOT
Time Frame:6 ± 2 weeks after End of Treatment
Safety Issue:
Description:MRD status by cell-free ctDNA assessment at EOT
Measure:PFS at 3 years
Time Frame:36 months after randomization
Safety Issue:
Description:Progression-Free Survival as assessed by the investigator
Measure:EFS at 3 years
Time Frame:36 months after randomization
Safety Issue:
Description:Event-Free Survival as assessed by the investigator
Measure:OS at 3 years
Time Frame:36 months after randomization
Safety Issue:
Description:Overall Survival
Measure:ORR as per INV at EOT
Time Frame:6 ± 2 weeks after End of Treatment
Safety Issue:
Description:Overall response rate defined as the proportion of patients with CR or PR as per Lugano 2014 criteria based on assessment at the end of the treatment by the INV

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:MorphoSys AG

Trial Keywords

  • DLBCL
  • CD19
  • monoclonal antibody
  • tafasitamab
  • lenalidomide
  • R-CHOP
  • Diffuse Large B-cell Lymphoma

Last Updated

May 27, 2021