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

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ClinicalTrials.gov Identifier: NCT04824092
Recruitment Status : Recruiting
First Posted : April 1, 2021
Last Update Posted : May 27, 2021
Sponsor:
Information provided by (Responsible Party):
MorphoSys AG

Tracking Information
First Submitted Date  ICMJE March 22, 2021
First Posted Date  ICMJE April 1, 2021
Last Update Posted Date May 27, 2021
Actual Study Start Date  ICMJE May 11, 2021
Estimated Primary Completion Date June 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tafasitamab + Lenalidomide + R-CHOP Versus R-CHOP in Newly Diagnosed High-intermediate and High Risk DLBCL Patients
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Diffuse Large B-cell Lymphoma
Intervention  ICMJE
  • 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  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 26, 2021)
880
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2026
Estimated Primary Completion Date June 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Andrea Sporchia, MD +49 89 89927 26994 Andrea.Sporchia@morphosys.com
Contact: Sascha Tillmanns Sascha.Tillmanns@morphosys.com
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Canada,   Colombia,   Czechia,   France,   Germany,   Hungary,   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
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04824092
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: No
Responsible Party MorphoSys AG
Study Sponsor  ICMJE MorphoSys AG
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Andrea Sporchia, MD MorphoSys AG
PRS Account MorphoSys AG
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP