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NVG-111: A phase 1/2 trial of a new treatment for people with relapsed or refractory chronic lymphocytic leukaemia, small lymphocytic lymphoma or mantle cell lymphoma

This is a phase 1 (early phase) trial. Little is known about the safety and effectiveness of this treatment. You might not benefit from the treatment, but the trial will give important information about this new treatment, which could help other people in the future.


Purpose of trial

The trial is in two parts:


Treatments

Everybody who takes part in this trial has treatment with NVG-111. You have it in addition to your existing treatment for CLL/SLL or mantle cell lymphoma, which continues during the trial.

NVG-111 is a type of treatment called a ‘bispecific antibody T-cell engager’. It attaches to a protein called ‘ROR1’ on cancer cells and also attaches to white blood cells called T cells. This may help your own immune system to destroy the cancer cells.

The trial is in two parts:

  • Part 1 is to find out the highest safe dose of NVG-111. This is done by ‘dose escalation’. Participants are treated in groups. The first few participants have the lowest dose of NVG-111. They have blood tests to measure the level of the drug in their body and they are carefully monitored for side effects. If the lowest dose doesn’t cause troublesome problems, they might have the dose increased for the next and subsequent cycles. The next few participants also have a slightly higher dose. This continues until the highest safe dose is found. The most effective safe dose is used in the second part of the trial.
  • Part 2 is to test how well the highest safe dose of NVG-111 works. People entering this part of the trial all have the same dose of NVG-111.

You have NVG-111 through a drip that runs continuously for 3 weeks followed by a 1 week break. The drip runs into a central line inserted in your arm or near your collar bone (a PICC or Hickman line). It is controlled by a small portable pump that you wear all the time in a bag or pouch around your waist or over your shoulder.

You have to stay in hospital for the first 4 days of treatment but you can have the rest of the treatment at home if you don’t have any problems. You go back to the hospital each week to have the pump programmed, checked and loaded with the study drug. You are told how to look after the pump and what to do if there is a problem.

If you have the dose of NVG-111 increased, you stay in hospital for another 4 days.

You have up to 3 cycles of treatment initially, with a possibility of up to 6 cycles depending on how your lymphoma responds.


Who can enter

Your consultant can give you advice on whether you might be suitable for this trial.

Around 90 people are needed for this trial.

You may be able to enter if:

  • You have chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) and:
    • your CLL/SLL has come back or not completely responded after at least 12 months of treatment with a BTK inhibitor (for example, ibrutinib or acalabrutinib) or 6 months of treatment with venetoclax
    • you have had at least one other previous course of treatment.
  • You have mantle cell lymphoma and:
    • your lymphoma has come back or not completely responded after at least 6 months of treatment with a BTK inhibitor (for example, ibrutinib or acalabrutinib)
    • you have had at least one other previous course of treatment
    • your lymphoma has spread to your bone marrow.
  • You no longer have significant side effects from any of your previous treatment.
  • You have had, or are willing to have, a biopsy of your lymphoma.
  • You already have, or are willing to have, a central line fitted to have your treatment.
  • You are well enough to take part in the trial.
  • Your blood and other health test results are satisfactory.
  • You and your partner are willing to use reliable contraception if there is any chance of you or your partner becoming pregnant.
  • You are 18 or over.

You won’t be able to enter if:

  • You have any health problems that your doctor thinks might make it unsafe for you to have the trial treatment.
  • Your CLL/SLL has changed (transformed) to a faster-growing type (Richter transformation).
  • Your lymphoma is in your central nervous system (CNS; brain and spinal cord).
  • You have any lumps of lymphoma that are bigger than 10cm across.
  • You have a high level of lymphocytes in your blood.
  • You’ve had autoimmune haemolytic anaemia (AIHA) or idiopathic thrombocytopenic purpura (ITP) within the last 8 weeks that are not under control.
  • You have HIV, hepatitis C, hepatitis B or COVID-19.
  • You have significant lung disease, heart disease, or a significant illness affecting your nervous system (including epilepsy, stroke, dementia or Parkinson’s disease).
  • You have had another cancer in the past, except certain localised cancers, early stage prostate cancer or cancer that has been in remission for at least 3 years.
  • You’ve had a stem cell transplant or donor lymphocyte infusion in the last 6 months.
  • You’ve had any treatment for CLL/SLL or mantle cell lymphoma in the past 4 weeks except ibrutinib, acalabrutinib or venetoclax.
  • You’ve had antibody therapy in the last 12 weeks.
  • You’ve had major surgery in the last 4 weeks.
  • You’ve had any live vaccines in the last 4 weeks.
  • You are having, or have recently had, treatment as part of another clinical trial.
  • You are having treatment for an infection.
  • You are pregnant or breastfeeding.
  • Any of the study drugs are not suitable for you.

Further information

More information about this trial is available at www.clinicaltrialsregister.eu/ctr-search/trial/2020-000820-20/GB