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

Ведущий спонсор: MorphoSys AG

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

• Diffuse Large B-cell Lymphoma

Тип вмешательства: Drug

Название вмешательства: Tafasitamab

Описание: Tafasitamab IV infusion will be administered as per the schedule specified in the respective arm.

Этикетка Arm Group: Tafasitamab plus lenalidomide in addition to R-CHOP

Другое имя: Monjuvi

Тип вмешательства: Drug

Название вмешательства: Lenalidomide

Описание: Lenalidomide PO will be administered as per the schedule specified in the respective arm.

Этикетка Arm Group: Tafasitamab plus lenalidomide in addition to R-CHOP

Тип вмешательства: Drug

Название вмешательства: Rituximab

Описание: Rituximab IV infusion will be administered as per the schedule specified in the respective arm.

Тип вмешательства: Drug

Название вмешательства: Cyclophosphamide

Описание: Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.

Тип вмешательства: Drug

Название вмешательства: Doxorubicin

Описание: Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.

Тип вмешательства: Drug

Название вмешательства: Vincristine

Описание: Vincristine IV infusion will be administered as per the schedule specified in the respective arm.

Тип вмешательства: Drug

Название вмешательства: Prednisone

Описание: Prednisone PO will be administered as per the schedule specified in the respective arm.

Тип вмешательства: Drug

Название вмешательства: Tafasitamab placebo

Описание: 0.9% saline solution IV infusion will be administered as per the schedule specified in the respective arm.

Этикетка Arm Group: Tafasitamab placebo plus lenalidomide placebo in addition to R-CHOP

Тип вмешательства: Drug

Название вмешательства: Lenalidomide placebo

Описание: Placebo matching to lenalidomide PO will be administered as per the schedule specified in the respective arm.

Этикетка Arm Group: Tafasitamab placebo plus lenalidomide placebo in addition to R-CHOP

Критерии:

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

Пол:

All

Минимальный возраст:

18 Years

Максимальный возраст:

80 Years

Здоровые волонтеры:

No

Фамилия: Associate Director, Clinical Development

Телефон: +1 617-404-7828

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

2022-01-01

Тип: Sponsor

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

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Метка: Tafasitamab plus lenalidomide in addition to R-CHOP

Тип: Experimental

Описание: 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

Метка: Tafasitamab placebo plus lenalidomide placebo in addition to R-CHOP

Тип: Placebo Comparator

Описание: 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

Распределение: Randomized

Модель вмешательства: Parallel Assignment

Первичное назначение: Treatment

Маскировка: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)