PRISM: a phase 1 study testing acalabrutinib in combination with AZD9150 or AZD6738 in people with high-grade non-Hodgkin lymphoma that has come back or has not responded to treatment

This is a phase 1 (early phase) trial of an experimental treatment. 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

This is a platform study, which means it can test several different treatments in several different diseases at the same time. It aims to find out if different targeted drugs could be safe and effective for people with high-grade non-Hodgkin lymphoma that has not responded (refractory) or has come back (relapsed) after previous treatment.

Initially, the trial is looking at acalabrutinib, in combination with one of two new treatments (AZD9150 and AZD6738), in people with relapsed or refractory high-grade non-Hodgkin lymphoma (including diffuse large B-cell lymphoma or DLBCL).

In future, other targeted drugs or different types of lymphoma might be added to the study.


Participants are given one of two treatments:

  • acalabrutinib plus AZD9150
  • acalabrutinib plus AZD6738.

You are told which treatment you are having and given information about it. If you have to stop the study treatment for any reason, you might be assessed to see if you are suitable for the other treatment.

  • AZD9150 is a cell signal blocker that targets a protein called STAT3. It works by blocking signals that tell cancer cells to grow, divide and survive.
  • AZD6738 is a cell signal blocker that targets a protein called ATR. It works by blocking signals that tell cancer cells to repair themselves. This can make the cancer cells die.
  • Acalabrutinib is a cell signal blocker that targets a protein called BTK.It works by blocking signals that help B cells to stay alive and divide.

You have AZD9150 as an intravenous infusion (by a drip into a vein). You have it three times in the first week of treatment and once a week from then on. You carry on having the treatment for up to 2 years unless your lymphoma gets worse.

You take AZD6738 and acalabrutinib orally (as capsules taken by mouth) twice a day.

Who can enter

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

Around 42 people are needed for this trial.

You may be able to enter if:

  • You have relapsed or refractory high-grade non-Hodgkin lymphoma, including DLBCL.
  • Your lymphoma is measurable by the tests used in the trial.
  • You have previously had at least one course of treatment for your lymphoma.
  • There are no other treatment options suitable for you that might cure your lymphoma.
  • You are well enough to take part in the trial.
  • Your blood and other health test results are satisfactory.
  • You are 18 or over.

You won’t be able to enter if:

  • Your lymphoma is in your central nervous system (CNS; brain and spinal cord).
  • You have any health problems that your doctor thinks might make it unsafe for you to have the trial treatment, including certain heart or lung conditions.
  • You have low blood pressure or high blood pressure that is not controlled by medications.
  • Your doctor thinks you might be at risk of experiencing problems with blood flow to your brain.
  • You are taking or have taken certain other drugs. Your doctor can tell you if this applies to you.
  • You have HIV, hepatitis C or hepatitis B.
  • You have had another cancer in the past, except certain localised cancers or cancer that was treated with the aim of curing it and has been in remission for more than 2 years.
  • You have active inflammatory bowel disease or other conditions that make it difficult for you to absorb nutrients.
  • You have had surgery to remove or bypass your stomach or remove your small bowel.
  • You are pregnant or breastfeeding.

Further information

More information about this trial is available at

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