A Randomized, Multicenter, Phase III Trial Comparing Treatment With R-mini-CHOP With R-mini-CHP + Polatuzumab Vedotin in Patients With Diffuse Large Cell B Cell Lymphoma

Study Overview
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Brief Summary
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This is a phase III, randomized, open-label, multicenter trial, conducted in Sweden, Norway, Finland, Denmark, Italy and Switzerland, in elderly patients with untreated diffuse large B-cell lymphoma. Elderly is defined as either ≥80 years of age, or ≥75 years and frail, according to a simplified Comprehensive Geriatric Assessment. Patients will be randomized 1:1 to either the standard treatment for this population, R-miniCHOP, or an experimental regimen, R-pola-miniCHP, where vincristine is substituted by an immunoconjugate, polatuzumab vedotin. The duration of the screening period is up to 4 weeks. The duration of active treatment is 18 weeks in both arms, and patients will be followed up to 36 months after end of treatment. Start of enrollment is planned in Q1 2020, and the last visit of the last patient included (end of trial) is estimated in Q1 2026.

Official Title
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R-MINI-CHOP Versus R-MINI-CHP in Combination With Polatuzumab-vedotin, as Primary Treatment for Patients With Diffuse Large B-cell Lymphoma, ≥80 Years, or Frail ≥75 Years - an Open Label Randomized Nordic Lymphoma Group Phase III Trial

Conditions
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DLBCL, Diffuse Large B Cell Lymphoma

Intervention / Treatment
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* Drug: R-pola-mini-CHP
* Drug: R-mini-CHOP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥80 years or frail ≥75 years, according to simplified comprehensive geriatric assessment Histologically confirmed lymphoma belonging to one of the following subtypes: diffuse large B-cell lymphoma, including transformation from an indolent lymphoma follicular lymphoma grade 3B T-cell/histiocyte-rich LBCL primary cutaneous DLBCL, leg type EBV-positive DLBCL, NOS primary mediastinal LBCL high grade B-cell lymphoma with MYC/BCL2 rearrangement Stage II-IV disease At least 1 measurable site of disease (>1.5 cm long axis) No previous treatment for lymphoma WHO performance status 0 - 3 (Grade 3 if related to DLBCL) Written informed consent Exclusion Criteria: Severe cardiac disease: NYHA grade 3-4 CNS involvement at diagnosis Uncontrolled serious infection Impaired liver (transaminases > 3x normal upper limit or bilirubin > 1.5 x normal upper limit, unless due to Gilbert´s syndrome) , renal (GFR<30ml/min) or other organ function not caused by lymphoma, which will interfere with the treatment. Absolute neutrophil count (ANC) <1000 cells/µL or platelets <100,000 cells/µL, unless due to lymphoma Any other prior malignancy than non-melanoma skin cancer or stage 0 (in situ) cervical carcinoma, unless treated with curative intent, and without relapse since 2 years, or low grade prostate cancer, not in need of treatment Psychiatric illness or condition which could interfere with their ability to understand the requirements of the study Known hypersensitivity to rituximab, polatuzumab vedotin, cyclophosphamide, vincristine or doxorubicin, or HACA against rituximab

Ages Eligible for Study
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Minimum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A - R-mini-CHOP<br>Cycles 1-6, duration 21 days Rituximab 375 mg/m2 i.v., day 1, cycle 1. 1400 mg s c OR 375 mg/m2 i. v. cycles 2-6 Cyclophosphamide 400 mg/m2 i.v., day 1, cycles 1-6 Doxorubicin 25 mg/m2 i.v., day 1, cycles 1-6 Vincristine 1 mg i.v. (total dose), day 1, cycles 1-6 Prednisone, 40 mg/m2 p.o, days 1-5, , cycles 1-6 | Drug: R-mini-CHOP<br>* Rituximab 375 mg/m2 i.v., day 1, cycle 1. 1400 mg s c OR 375 mg/m2 i. v. cycles 2-6 Cyclophosphamide 400 mg/m2 i.v., day 1, cycles 1-6 Doxorubicin 25 mg/m2 i.v., day 1, cycles 1-6 Vincristine 1 mg i.v. (total dose), day 1, cycles 1-6 Prednisone, 40 mg/m2 p.o, days 1-5, , cycles 1-6<br>|
| Experimental: Arm B - R-pola-mini-CHP<br>Cycles 1-6, duration 21 days Rituximab 375 mg/m2 i.v., day 1, cycle 1. 1400 mg s c OR 375 mg/m2 i. v. cycles 2-6 Cyclophosphamide 400 mg/m2 i.v., day 1, cycles 1-6 Doxorubicin 25 mg/m2 i.v., day 1, cycles 1-6 Prednisone, 40 mg/m2 p.o, days 1-5, , cycles 1-6 Polatuzumab vedotin 1.8 mg/kg i.v day 1 cycles 1-6 | Drug: R-pola-mini-CHP<br>* Rituximab 375 mg/m2 iv, day 1, cycle 1. 1400 mg s c OR 375 mg/m2 iv cycles 2-6 Cyclophosphamide 400 mg/m2 iv, day 1, cycles 1-6 Doxorubicin 25 mg/m2 iv , day 1, cycles 1-6 Prednisone, 40 mg/m2 po, days 1-5, cycles 1-6 - round up to nearest 25 mg Polatuzumab vedotin 1.8 mg/kg iv day 1 cycles 1-6<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS). | The primary end point of this study is PFS. The null hypothesis is that pola-R-mini-CHP is equivalent to R-mini-CHOP. PFS is defined as the interval between registration date and date of documented progression or lack of response, first relapse, or death of any cause. Otherwise, patients will be censored at the last date they were known to be alive. For patients with PD as best response, PFS is defined as 1 day. | 2 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DLBCL, Diffuse Large B Cell Lymphoma