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

Phase 3

Recruiting

• Conditions: DLBCL; Diffuse Large B Cell Lymphoma
• Interventions: Drug: R-mini-CHOP; Drug: R-pola-mini-CHP

• Registration Number: NCT04332822
• Lead Sponsor: Nordic Lymphoma Group

Brief Summary

This is a phase III, randomized, open-label, multicenter trial, conducted in Sweden, Norway, Finland, Denmark, Italy, Australia and New Zealand, 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 2027.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-04-01
• Study First Submitted QC: 2020-04-01
• Study First Posted: 2020-04-03
• Study Start: 2020-08-19
• Status Verified: 2024-02
• Last Update Submitted: 2024-08-14
• Last Update Posted: 2024-08-15
• Primary Completion: 2025-12-28
• Study Completion: 2028-12-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

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
• Peripheral neuropathy grade ≥ 2

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A - R-mini-CHOP	R-mini-CHOP	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
Arm B - R-pola-mini-CHP	R-pola-mini-CHP	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

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS).	2 years.	Interval between randomization date and date of documented progression, first relapse, or death of any cause

Trial Locations

Locations (69)

Tweed Valley Hospital; 🇦🇺 Cudgen, Australia

Border Medical Oncology Research Unit; 🇦🇺 Albury, Australia

Royal Prince Alfred Hospital; 🇦🇺 Camperdown, Australia

Coffs Harbour; 🇦🇺 Coffs Harbour, Australia

Concord Repatriation General Hospital; 🇦🇺 Concord, Australia

The Canberra Hospital; 🇦🇺 Garran, Australia

Royal Hobart Hospital; 🇦🇺 Hobart, Australia

Liverpool; 🇦🇺 Liverpool, Australia

Bendigo; 🇦🇺 Melbourne, Australia

Northern Health; 🇦🇺 Melbourne, Australia

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