A trial looking at chemotherapy and rituximab for people with diffuse large B cell non Hodgkin lymphoma or Burkitt's lymphoma (R-CODOX-M/IVAC for DLBCL or BL)

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

Cancer type:

High grade lymphoma

Lymphoma

Non-Hodgkin lymphoma

Status:

Closed

Phase:

Phase 2

This trial is looking at a new combination of chemotherapy drugs with rituximab for 2 types of non Hodgkin lymphoma (NHL). These are called diffuse large B cell lymphoma and Burkitt's lymphoma. The treatment is called R-CODOX-M/IVAC for short.

This trial is for people who have a medium or high risk of their lymphoma coming back after treatment. The standard treatment for diffuse large B cell NHL is a combination of chemotherapy and a type of monoclonal antibody called rituximab. This is called R-CHOP. It is a successful treatment for many. But some people’s lymphoma comes back or continues to grow despite treatment. Doctors want to improve on this and to control the lymphoma for longer.

CODOX-M/IVAC includes the chemotherapy drugs cyclophosphamide, doxorubicin, vincristine, methotrexate, etoposide, ifosfamide and cytarabine. Trials have already shown that this combination of drugs works well for people with Burkitt’s lymphoma. In this trial, researchers want to see if adding rituximab (R-CODOX-M/IVAC) will improve the treatment for Burkitt's lymphoma. And they think it may work well for diffuse large B cell lymphoma too.

This trial aims to find out how well R-CODOX-M/IVAC works for people with diffuse large B cell NHL and Burkitt's lymphoma. It will also look at the side effects to find out how this treatment affects their quality of life.

Who can enter

You can enter this trial if you

Have recently been diagnosed with diffuse large B cell lymphoma or Burkitt's lymphoma
Have a protein called CD20 on your lymphoma cells ('CD20 positive' NHL) - your doctor will be able to tell you if this applies to you
Have stage 2, 3 or 4 NHL and your doctor thinks that you are at a medium (intermediate) or high risk of your lymphoma coming back after treatment
Are at least 18 years old but less than 66 years old
Have satisfactory blood test results
Are well enough to have treatment
Are willing to use reliable contraception during the trial if there is any chance you or your partner could become pregnant

You cannot enter this trial if you

Have already had chemotherapy or radiotherapy for your lymphoma
Have already had any treatment as part of a trial for your lymphoma
Have T cell lymphoma
Have had a low grade lymphoma in the past
Have heart failure or uncontrolled angina, or have had either of these in the past
Are unable to have the chemotherapy drugs doxorubicin or vincristine for medical reasons
Have any serious illness that is not controlled properly with treatment
Have, or have had, any other type of cancer (apart from non-melanoma skin cancer or carcinoma in situ of the cervix) in the last 10 years
Are hepatitis B, hepatitis C or HIV positive (some people with Burkitt's lymphoma who are HIV positive may be able to take part - the trial doctor can discuss this with you)

Trial design

This phase 2 trial will recruit 150 people with diffuse large B cell NHL or Burkitt's lymphoma. All patients will have treatment with R-CODOX-M/IVAC (the letters refer to the different drug names).

During the first 2 weeks of your treatment you will have rituximab, cyclophosphamide, vincristine, doxorubicin and methotrexate (R-CODOX-M). You will have these drugs through a drip into a vein.

You will also have cytarabine injected into the fluid around your spinal cord. This is called an intrathecal injection and goes into the lower part of your back. It helps to treat or prevent lymphoma spread to the central nervous system Open a glossary item . After these 2 weeks of treatment, you have no treatment for the next 2 weeks. This 4 week period is called a cycle of treatment.

In week 5 you start R-IVAC treatment. You will have rituximab, etoposide, ifosfamide and cytarabine through a drip into a vein. If you have high risk lymphoma, you will also have cytarabine into the spinal fluid as before. After this week of treatment you then have no treatment for the next 3 weeks. This 4 week period is your second cycle of treatment.

You then have a further cycle of R-CODOX-M, followed by another cycle of R-IVAC. So you have 4 cycles of treatment in total over about 4 months.

After your 4th cycle of treatment you will have 2 more doses of rituximab. You have these about 3 weeks and 6 weeks after your last cycle.

During every cycle you will also have an injection of G-CSF (granulocyte colony stimulating factor). This is an injection just under your skin either into your stomach, arm or thigh. It helps your bone marrow to make new white blood cells. If your bone marrow recovers after each treatment, you are more likely to have your next cycle on time.

The treatment schedule in this trial is quite complicated. For each cycle your doctor or nurse will explain in detail when you have each drug and how often.

Hospital visits

Before you start your treatment, a doctor will examine you and you will have various tests. These tests may include

Bone marrow test
Blood tests
CT scan of your neck, chest, tummy (abdomen) and pelvis
An ECG (heart trace)
A heart ultrasound (echocardiogram ) or MUGA scan

During your treatment you will probably stay in hospital for about 2 weeks for each cycle of treatment. Or sometimes longer if you are unwell. You have blood tests before and during each cycle of treatment.

After your treatment has finished you see a doctor every month for the first 4 months, then every 2 months for the first year. These appointments gradually become less often. They will be 6 monthly after year 4, then yearly after that.

You have a CT scan at the end of your treatment, another after 4 months and another 1 year later.

The trial doctors will ask for a sample of the lymphoma that was taken when you were first diagnosed. This will be stored and may be used for future research. This part of the trial is optional. You do not have to agree to this if you don’t want to. You will still be able to take part in the trial.

Side effects

All treatment have side effects. The most common side effects of the drugs used in this trial include

A drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
Sore mouth (mucositis)
Diarrhoea
Feeling or being sick
Hair loss, this usually grows back shortly after chemotherapy has stopped
Numbness and tingling in hands and feet (peripheral neuropathy), this is usually temporary, but can be permanent
Fever or chills after first dose of rituximab

You can read more about the side effects of cyclophosphamide, doxorubicin, vincristine, methotrexte, etoposide, ifosfamide, cytarabine and rituximab on CancerHelp UK. The trial doctor or nurse will explain side effects to you in more detail.