Diffuse Large B-cell Lymphoma
Conditions
Keywords
DLBCL, CD19, monoclonal antibody, tafasitamab, lenalidomide, R-CHOP, Diffuse Large B-cell Lymphoma
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
Interventions
DRUGTafasitamab
Tafasitamab IV infusion will be administered as per the schedule specified in the respective arm.
DRUGLenalidomide
Lenalidomide PO will be administered as per the schedule specified in the respective arm.
DRUGRituximab
Rituximab IV infusion will be administered as per the schedule specified in the respective arm.
DRUGCyclophosphamide
Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.
DRUGDoxorubicin
Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.
DRUGVincristine
Vincristine IV infusion will be administered as per the schedule specified in the respective arm.
DRUGPrednisone
Prednisone PO will be administered as per the schedule specified in the respective arm.
DRUGTafasitamab placebo
0.9% saline solution IV infusion will be administered as per the schedule specified in the respective arm.
Placebo matching to lenalidomide PO will be administered as per the schedule specified in the respective arm.
Sponsors
Incyte Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS-INV | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| EFS-INV | 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 | 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 | 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 | 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 | 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) | 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 | 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 | 36 months after randomization | Event-Free Survival as assessed by the investigator |
| PFS at 3 years | 36 months after randomization | Progression-Free Survival as assessed by the investigator |
| OS at 3 years | 36 months after randomization | Overall Survival |
Countries
Argentina, Australia, Austria, Canada, Colombia, Czechia, France, Germany, Hungary, Ireland, Israel, Italy, Japan, Malaysia, New Zealand, Philippines, Poland, Romania, Russia, Serbia, Slovakia, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORIncyte Medical Director
Incyte Corporation
Outcome results
None listed