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)
(Protocol No. : MOR208C310)
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)
Suzukawa Kazumi
Incyte Biosciences Japan G.K.
Tokyo Midtown Hibiya, 1-1-2 Yurakucho, Chiyoda-ku, Tokyo, Japan
+81-120-094-139
jpmedinfo@incyte.com
Medical Information Center
Incyte Biosciences Japan G.K.
Tokyo Midtown Hibiya, 1-1-2 Yurakucho, Chiyoda-ku, Tokyo, Japan
+81-120-094-139
jpmedinfo@incyte.com
Not Recruiting
July. 14, 2022
July. 14, 2022
35
Interventional
randomized controlled trial
double blind
active control
parallel assignment
treatment purpose
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
18age old over
80age old under
Both
Diffuse Large B-cell Lymphoma
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
PFS-INV
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
Incyte Biosciences Japan G.K.
National Hospital Organization Kyushu Medical Center Institutional Review Board
1-8-1 Jigyohama, Chuo, Fukuoka, Fukuoka
+81-92-852-0700
Approval
May. 26, 2022
No
NCT04824092
ClinicalTrials.gov
U.S.A/Argentina/Australia/Austria/Canada/Colombia/Czechia/France/Germany/Hungary/Ireland/Israel/Italy/Republic of Korea/Malaysia/New Zealand/Philippines/Poland/Romania/Russian Federation/Serbia/Slovakia/Spain/Taiwan/Thailand/Turkey/Ukraine/United Kingdom/Hong Kong
