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

• ClinicalTrials.gov Identifier: NCT04824092
• Recruitment Status: Active, not recruiting
• First Posted: April 1, 2021
• Last Update Posted: April 6, 2023
• Sponsor: MorphoSys AG
• Information provided by (Responsible Party): MorphoSys AG

Tracking Information

• First Submitted Date: March 22, 2021
• First Posted Date: April 1, 2021
• Last Update Posted Date: April 6, 2023
• Actual Study Start Date: May 11, 2021
• Estimated Primary Completion Date: June 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 3, 2023)

PFS-INV [ Time Frame: Time from date of randomization until Progressive Disease or death from any cause. In this trial, the primary endpoint is PFS as assessed by the investigator (up to 43 months) ]

Progression-Free Survival as assessed by the investigator using the Lugano Response Criteria for Malignant Lymphoma

Original Primary Outcome Measures (submitted: March 26, 2021)

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) ]

Progression-Free Survival as assessed by the investigator using the Lugano Response Criteria for Malignant Lymphoma

Current Secondary Outcome Measures (submitted: February 3, 2023)

• 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) ]
  Event-Free Survival as assessed by the investigator using the Lugano Response Criteria for Malignant Lymphoma
• OS [ Time Frame: From randomization until the date of death from any cause (up to 62 months) ]
  Overall Survival
• Metabolic PET-negative CR-rate at EOT by BIRC [ Time Frame: End of treatment, 4-8 weeks after last dose ]
  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
• Metabolic PET-negative CR-rate at EOT by INV [ Time Frame: End of treatment, 4-8 weeks after last dose ]
  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
• ORR as per INV at EOT [ Time Frame: 6 ± 2 weeks after End of Treatment ]
  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
• Time to next anti-lymphoma treatment (TTNT) [ Time Frame: From randomization date to start of next anti-lymphoma therapy (for any reason including disease progression, treatment toxicity, and patient preference) or death due to any cause, whatever comes first (up to 43 months) ]
  TTNT is defined as the time from randomization date to start of next anti-lymphoma therapy (for any reason including disease progression, treatment toxicity, and patient preference) or death due to any cause, whatever comes first.
• Duration of Complete Response (CR) as assessed by the investigator [ Time Frame: From the date of the first occurrence of a documented CR, to the date of progression, relapse, or death from any cause, whichever is earlier (up to 43 months) ]
  Duration of CR is defined as the time from the date of the first occurrence of a documented CR, to the date of progression, relapse, or death from any cause, whichever is earlier for the subgroup of patients with a Best Overall Response (BOR) of CR.
• EFS at 3 years [ Time Frame: 36 months after randomization ]
  Event-Free Survival as assessed by the investigator
• PFS at 3 years [ Time Frame: 36 months after randomization ]
  Progression-Free Survival as assessed by the investigator
• OS at 3 years [ Time Frame: 36 months after randomization ]
  Overall Survival

Original Secondary Outcome Measures (submitted: March 26, 2021)

• 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) ]
  Event-Free Survival as assessed by the investigator using the Lugano Response Criteria for Malignant Lymphoma
• OS [ Time Frame: From randomization until the date of death from any cause (up to 62 months) ]
  Overall Survival
• Metabolic PET-negative CR-rate at EOT by BIRC [ Time Frame: End of treatment, 4-8 weeks after last dose ]
  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
• Metabolic PET-negative CR-rate at EOT by INV [ Time Frame: End of treatment, 4-8 weeks after last dose ]
  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
• MRD status at EOT [ Time Frame: 6 ± 2 weeks after End of Treatment ]
  MRD status by cell-free ctDNA assessment at EOT
• PFS at 3 years [ Time Frame: 36 months after randomization ]
  Progression-Free Survival as assessed by the investigator
• EFS at 3 years [ Time Frame: 36 months after randomization ]
  Event-Free Survival as assessed by the investigator
• OS at 3 years [ Time Frame: 36 months after randomization ]
  Overall Survival
• ORR as per INV at EOT [ Time Frame: 6 ± 2 weeks after End of Treatment ]
  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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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)
• Brief Summary: 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
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Diffuse Large B-cell Lymphoma

Intervention

• Drug: Tafasitamab
  Tafasitamab IV infusion will be administered as per the schedule specified in the respective arm.
  Other Name: Monjuvi
• Drug: Lenalidomide
  Lenalidomide PO will be administered as per the schedule specified in the respective arm.
• Drug: Rituximab
  Rituximab IV infusion will be administered as per the schedule specified in the respective arm.
• Drug: Cyclophosphamide
  Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.
• Drug: Doxorubicin
  Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.
• Drug: Vincristine
  Vincristine IV infusion will be administered as per the schedule specified in the respective arm.
• Drug: Prednisone
  Prednisone PO will be administered as per the schedule specified in the respective arm.
• Drug: Tafasitamab placebo
  0.9% saline solution IV infusion will be administered as per the schedule specified in the respective arm.
• Drug: Lenalidomide placebo
  Placebo matching to lenalidomide PO will be administered as per the schedule specified in the respective arm.

Study Arms

• Experimental: Tafasitamab plus lenalidomide in addition to R-CHOP

  Patients 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

  Interventions:

  • Drug: Tafasitamab
  • Drug: Lenalidomide
  • Drug: Rituximab
  • Drug: Cyclophosphamide
  • Drug: Doxorubicin
  • Drug: Vincristine
  • Drug: Prednisone
• Placebo Comparator: Tafasitamab placebo plus lenalidomide placebo in addition to R-CHOP

  Patients 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

  Interventions:

  • Drug: Rituximab
  • Drug: Cyclophosphamide
  • Drug: Doxorubicin
  • Drug: Vincristine
  • Drug: Prednisone
  • Drug: Tafasitamab placebo
  • Drug: Lenalidomide placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 4, 2023): 899
• Original Estimated Enrollment (submitted: March 26, 2021): 880
• Estimated Study Completion Date: May 2026
• Estimated Primary Completion Date: June 2025 (Final data collection date for primary outcome measure)

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. HGBL-NOS
  8. DLBCL coexistent with either follicular lymphoma (FL) of any grade, gastric MALT lymphoma or non-gastric MALT lymphoma
  9. 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 B Cell 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 50% as 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Canada, Colombia, Czechia, France, Germany, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Malaysia, New Zealand, Philippines, Poland, Romania, Russian Federation, Serbia, Slovakia, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States

Administrative Information

• NCT Number: NCT04824092
• Other Study ID Numbers: MOR208C310
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: MorphoSys AG
• Original Responsible Party: Same as current
• Current Study Sponsor: MorphoSys AG
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: MorphoSys AG
• Verification Date: April 2023