A Study to Evaluate the Safety and Efficacy of Polatuzumab Vedotin in Combination With Rituximab, Gemcitabine and Oxaliplatin Compared to Rituximab, Gemcitabine and Oxaliplatin Alone in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (POLARGO)

Roche

Status and phase

Completed

Phase 3

Conditions

Diffuse Large B-Cell Lymphoma

Treatments

Drug: Gemcitabine

Drug: Polatuzumab Vedotin

Drug: Oxaliplatin

Drug: Rituximab

Study type

Interventional

Funder types

Industry

Identifiers

NCT04182204

2018-003727-10 (EudraCT Number)

MO40598

Details and patient eligibility

About

This study is a multicenter, open-label study of polatuzumab vedotin administered by intravenous (IV) infusion in combination with rituximab, gemcitabine and oxaliplatin (R-GemOx) in participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The study comprises of two stages: a safety run-in stage and a randomized controlled trial (RCT).

Full description

The safety run-in stage (Stage 1) will assess the safety of polatuzumab vedotin plus rituximab, gemcitabine and oxaliplatin (Pola-R-GemOx) in 10 participants. The randomized controlled trial (RCT) (Stage 2) will compare Pola-R-GemOx versus R-GemOx alone using overall survival (OS). This is an event-driven trial.

Enrollment

270 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Histologically-confirmed diffuse large B-cell lymphoma, not otherwise specified (NOS) or history of transformation of indolent disease to DLBCL
Relapsed disease (disease that has recurred following a response that lasted ≥ 6 months from completion of the last line of therapy) or refractory disease (disease that did not respond to or that progressed during therapy or progressed within 6 months (< 6 months) of prior therapy)
At least one (≥ 1) line of prior systemic therapy:
Patients may have undergone autologous hematopoietic stem cell transplantation (HSCT) prior to recruitment; In such cases, salvage chemotherapy (e.g., rituximab, dexamethasone, cytarabine, and cisplatin [R-DHAP] and rituximab, ifosfamide, carboplatin, and etoposide phosphate [R-ICE]) will be counted as one line of therapy and conditioning chemotherapy (e.g., BEAM) followed by consolidative autologous HSCT will be counted as one line of therapy
Patients may have undergone allogeneic HSCT prior to recruitment, so long as they are off all immunosuppressive therapy and have no active GVHD; In such cases, salvage chemotherapy (e.g., R-DHAP and R-ICE) will be counted as one line of therapy and conditioning chemotherapy (e.g., carmustine, etoposide, cytarabine, and melphalan [BEAM]) followed by allogeneic HSCT will be counted as a separate line of therapy
Participants may have undergone CAR T-cell therapy prior to recruitment. In such cases, cell collection, conditioning chemotherapy, and infusion will be counted as one line of therapy.
Local therapies (e.g., radiotherapy) will not be considered as lines of treatment
For participants with a history of the transformation of indolent disease to DLBCL, it is preferred that participants have received at least one treatment for the transformed lymphoma. However, if there are cases where the participants have received an anthracycline-containing chemotherapy regimen (such as R-CHOP) for the indolent lymphoma only, then these participants can be considered as eligible.
At least one bi-dimensionally measurable lesion, defined as > 1.5 cm in its longest dimension as measured by CT or MRI
Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2
Adequate hematological function
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm,

Exclusion criteria

History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products
Contraindication to rituximab, gemcitabine or oxaliplatin
Peripheral neuropathy assessed to be > Grade 1 according to NCI CTCAE v5.0
Prior use of polatuzumab vedotin or a gemcitabine plus platinum-based agent combination, recent participation in a clinical trial, and/or treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy within 2 weeks
Planned autologous or allogenic stem cell transplantation or CAR T-cell therapy at time of recruitment
Primary or secondary central nervous system (CNS) lymphoma
Richter's transformation or prior CLL
Abnormal laboratory values or health conditions, as assessed by the investigator, any known conditions preventing adherence to protocol or active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
Vaccination with a live vaccine within 4 weeks prior to treatment
Recent major surgery (within 6 weeks before the start of Cycle 1 Day 1) other than for diagnosis
Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
Pregnant or breastfeeding, or intending to become pregnant during the study or within 12 months after the last dose of study drug
Women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study drug

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

270 participants in 3 patient groups

Pola-R-GemOx (Stage 1)

Experimental group

Description:

Participants will receive polatuzumab vedotin 1.8 milligrams per kilogram (mg/kg) for a maximum dose of 240 mg per cycle (mg/cycle) administered intravenously (IV) and rituximab 375 milligrams per square meter (mg/m\^2) administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m\^2 administered IV and oxaliplatin 100 mg/m\^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.

Treatment:

Drug: Rituximab

Drug: Oxaliplatin

Drug: Gemcitabine

Drug: Polatuzumab Vedotin

Pola-R-GemOx (Stage 2)

Experimental group

Description:

Participants will receive polatuzumab vedotin 1.8 mg/kg for a maximum dose of 240 mg/cycle administered IV and rituximab 375 mg/m\^2 administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m\^2 administered IV and oxaliplatin 100 mg/m\^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.

Treatment:

Drug: Rituximab

Drug: Oxaliplatin

Drug: Gemcitabine

Drug: Polatuzumab Vedotin

R-GemOx (Stage 2)

Active Comparator group

Description:

Participants will receive rituximab 375 mg/m\^2 administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m\^2 administered IV and oxaliplatin 100 mg/m\^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.

Treatment:

Drug: Rituximab

Drug: Oxaliplatin

Drug: Gemcitabine

Trial documents