Purpose of trial
The aim of this trial is to compare the safety and effectiveness of replacing vincristine (a chemotherapy drug in R-CHOP) with polatuzumab vedotin as part of first-line treatment for DLBCL.
Polatuzumab vedotin is an antibody-drug conjugate. It comprises a strong anti-cancer drug joined to an antibody, which allows the drug to be delivered directly to the cancer cells.
R-CHOP is the most common first-line treatment regimen (combination of drugs) for people with DLBCL and includes:
- the antibody treatment rituximab (R)
- three chemotherapy drugs: cyclophosphamide (C), doxorubicin (H) and vincristine (O)
- the steroid prednisolone (P).
There are two treatment groups in this trial:
- standard treatment group: R-CHOP plus a placebo (dummy treatment) instead of polatuzumab vedotin
- polatuzumab vedotin group: R-CHP (without vincristine), plus a placebo instead of vincristine, plus polatuzumab vedotin.
You are randomised (randomly assigned a group by computer) to decide which group you are in. You can’t choose which group you are in and you will not be told whether you are having polatuzumab vedotin or vincristine.
Both groups have a placebo in this trial so you have the same number of drugs regardless of which group you are in. You have a placebo for polatuzumab vedotin or vincristine depending which group you are in. The placebos look the same as the active treatments so you can’t tell whether you are having polatuzumab vedotin or vincristine. This is known as ‘blinding’ and reduces any bias towards a certain treatment due to your feelings or your doctor’s feelings about it. You are given information about all of the treatments in this trial.
Most of the drugs are given intravenously (into a vein). You also take some drugs as tablets.
You have treatment in cycles, where a cycle is 3 weeks (21 days) long. You have up to 8 cycles of treatment.
For cycles 1 to 6, you have:
- Polatuzumab vedotin or vincristine (depending which group you are in), placebo, rituximab and the remaining chemotherapy drugs all given intravenously on day 1 of each cycle.
- Prednisolone tablets for the first 5 days of each cycle.
For cycles 7 and 8, you have rituximab alone on day 1 of each cycle.
Who can enter
Your consultant can give you advice on whether you might be suitable for this trial.
Approximately 875 people are needed for this trial worldwide.
You may be able to enter if:
- You have diffuse large B-cell lymphoma (DLBCL), or a rare type of large B-cell lymphoma, such as double-hit lymphoma, triple-hit lymphoma, or high-grade lymphoma not otherwise specified.
- Your lymphoma cells have CD20, the target for rituximab.
- A sample of your biopsy is available for tests.
- You have not yet received treatment for your lymphoma.
- You are well enough to take part in the trial.
- Your blood and other health test results are satisfactory.
- You are 18 to 80 years old.
You won’t be able to enter if:
- You’ve had a low-grade (slow-growing or ‘indolent’) lymphoma or follicular lymphoma grade 3b in the past.
- You have grey-zone lymphoma, primary mediastinal B-cell lymphoma (PMBL), Burkitt lymphoma, lymphoma in your central nervous system (CNS), primary effusion DLBCL or skin (cutaneous) lymphoma.
- You’ve had anti-cancer treatment in the last 5 years for any condition, or you have previously had rituximab or another anti-CD20 antibody treatment.
- You’ve had an antibody treatment in the last 3 months.
- You are taking steroid treatment at greater than 30mg per day of prednisone or the equivalent dose of another steroid, unless it is to control the symptoms of your lymphoma.
- You’ve had a live vaccine in the last 28 days.
- You’ve had any other experimental treatment in the last 28 days.
- You’ve had another cancer which could make it difficult to interpret the results of the trial.
- You’ve had a bad reaction to one of the trial drugs or their ingredients in the past.
- You’ve had an organ transplant.
- You have peripheral neuropathy (nerve damage) unless it is mild, or certain other nerve problems.
- You have any health problems that your doctor thinks might make it unsafe for you to have the trial treatment or might make it difficult to interpret the results of the trial, for example heart problems, lung problems or liver problems.
- You have an active infection or you’ve had a serious infection in the last 2 weeks.
- You’ve had major surgery in the last 4 weeks unless it was to diagnose your lymphoma.
- You’ve had radiotherapy to your chest in the past.
- You have HIV or active hepatitis B or hepatitis C, active or previous tuberculosis, or human T-lymphotropic virus 1 (HTLV-1). Your doctor can advise on this.
- You are pregnant or breastfeeding.
More information about this trial is available at www.clinicaltrials.gov/ct2/show/study/NCT03274492