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)

JRCT ID: jRCT2071220021

Registered date:24/06/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Diffuse Large B-cell Lymphoma
• Date of first enrollment: 14/07/2022
• Target sample size: 880
• Countries of recruitment: U.S.A,Japan,Argentina,Japan,Australia,Japan,Austria,Japan,Canada,Japan,Colombia,Japan,Czechia,Japan,France,Japan,Germany,Japan,Hungary,Japan,Ireland,Japan,Israel,Japan,Italy,Japan,Republic of Korea,Japan,Malaysia,Japan,New Zealand,Japan,Philippines,Japan,Poland,Japan,Romania,Japan,Russian Federation,Japan,Serbia,Japan,Slovakia,Japan,Spain,Japan,Taiwan,Japan,Thailand,Japan,Turkey,Japan,Ukraine,Japan,United Kingdom,Japan,Hong Kong,Japan
• Study type: Interventional

Intervention(s)

1. 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

2. 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

Outcome(s)

• Primary Outcome: PFS-INV

Secondary Outcome

1. EFS-INV
2. Overall Survival(OS)
3. Metabolic PET-negative CR-rate at EOT by BIRC
4. Metabolic PET-negative CR-rate at EOT by INV
5. ORR as per INV at EOT
6. Time to next anti-lymphoma treatment (TTNT)
7. Duration of Complete Response (CR) as assessed by the investigator
8. EFS at 3 years
9. PFS at 3 years
10. OS at 3 years

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 80age old
• Gender: Both

Include 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

Exclude criteria

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

Related Information

• Primary Sponsor: Ueda Eiji
• Secondary ID(s): NCT04824092