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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

NCT04332822

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Double-Hit Lymphoma
  • EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • Grade 3b Follicular Lymphoma
  • Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type
  • Primary Mediastinal B-Cell Lymphoma
  • T-Cell/Histiocyte-Rich Large B-Cell Lymphoma
  • Transformed Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: NLG-LBC7 POLAR BEAR
  • NCT ID: NCT04332822

Conditions

  • DLBCL
  • Diffuse Large B Cell Lymphoma

Interventions

DrugSynonymsArms
R-pola-mini-CHPArm B - R-pola-mini-CHP
R-mini-CHOPArm A - R-mini-CHOP

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Arm A - R-mini-CHOPActive ComparatorCycles 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
  • R-mini-CHOP
Arm B - R-pola-mini-CHPExperimentalCycles 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
  • R-pola-mini-CHP

Eligibility Criteria

        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:

               1. diffuse large B-cell lymphoma, including transformation from an indolent lymphoma

               2. follicular lymphoma grade 3B

               3. T-cell/histiocyte-rich LBCL

               4. primary cutaneous DLBCL, leg type

               5. EBV-positive DLBCL, NOS

               6. primary mediastinal LBCL

               7. 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:75 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS).
Time Frame:2 years.
Safety Issue:
Description: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.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Nordic Lymphoma Group

Trial Keywords

  • DLBCL
  • Diffuse Large B Cell Lymphoma

Last Updated

April 1, 2020