ADMIRE Trial Version 1.0

• Research type

  Research Study

• Full title

  ADMIRE: Does the Addition of Mitoxantrone Improve Response. A randomised, phase II trial of fludarabine, cyclophosphamide and rituximab (FCR) +/- mitoxantrone (M) in previously untreated chronic lymphocytic leukaemia.

• IRAS ID

  10986

• Contact name

• Sponsor organisation

  THE LEEDS TEACHING HOSPITALS NHS TRUST

• Eudract number

  2008-006342-25

• ISRCTN Number

  42165735

• Research summary

  Chronic Lymphocytic Leukaemia (CLL) is the most common leukaemia affecting 6 in 100,000 people per year in the UK. In CLL the lymphocytes, a type of blood cell, become ??cancerous? and grow out of control. Patients with CLL develop very large glands, high lymphocyte counts in the blood, failure of the bone marrow to make normal blood cells due to replacement with CLL, infections, severe tiredness, weight loss and sweating. The current treatment for CLL usually involves two different chemotherapy drugsfluarabine and cyclophosphamide or ??FC?) given together, every month for 6 months. Although most patients respond to FC, the chemotherapy is not able to kill every CLL cell meaning that patients eventually relapse and require further treatment. The time until relapse depends on the depth of remission. Most patients who require therapy will eventually die of CLL and so more effective treatments are urgently needed.Rituximab is an antibody which targets CLL cells and works in a different way to chemotherapy. It appears that combining rituximab with chemotherapy results in more effective CLL cell killing, with more patients responding and possibly prolonging the time until further treatment. Mitoxantrone (M) is a chemotherapy drug and recent evidence suggests that adding this drug to the FC combination may also improve the effectiveness of treatment.This trial will recruit patients who have not yet received any treatment for their disease. It will assess the response of patients who are treated witfluarabine, cyclophosphamide and rituximab (FCR) compared with the response of patients who receivfluarabine, cyclophosphamide, rituximab and mitoxantrone (FCM-R). If it appears that there is a difference in response between the two treatment groups, then a large trial is planned which will compare the time taken for disease progression to occur between the two treatment groups.

  Lay summary of study results: About this trial When this trial was initiated in 2009 doctors usually treated CLL with 2 chemotherapy drugs called fludarabine and cyclophosphamide in combination with a targeted cancer drug (a biological therapy) called rituximab. Doctors call this combination FCR.
  Earlier trials suggested that adding a chemotherapy drug called mitoxantrone to FCR might be a useful treatment for CLL. Doctors call this combination FCM-R.
  The doctors in this trial thought that this combination would help to lower the number of leukaemia cells that can be left behind after treatment. Remaining cancer cells are called ‘minimum residual disease’ or MRD. An undetectable MRD level means the leukaemia is less likely to come back.

  The aims of this trial were to find:
  • if FCM-R was better than FCR for people with newly diagnosed CLL
  • more about the side effects

  Summary of results
  The team found that FCM-R wasn’t better than FCR for people with newly diagnosed CLL.

  This was a phase 2 trial. It was a randomised trial. The 215 people who took part were put into 1 of 2 treatment groups by a computer. Neither they or their doctor chose which group they were in:
  • 107 people were in the FCR group
  • 108 people were in the FCM-R group

  After treatment the team looked at how many people in each group had no sign of their leukaemia (a complete response). They found that:
  • 60 out of the 107 people who had FCR had a complete response
  • 65 out of the 108 people who had FCM-R had a complete response

  3 months after finishing treatment everyone had a bone marrow test. This was to assess the minimum residual disease (MRD) in each group. They found that there was a very small amount or no MRD in:
  • 54 people who had FCR
  • 47 people who had FCM-R

  After an average follow up of 5 years the researchers found no significant difference between the 2 groups when they looked at:
  • the number of people who were alive and had no sign of leukaemia
  • the total number of people who were alive

  The side effects of FCR and FCM-R were similar. The worst side effects people had were infections.
  Some people in both groups didn’t complete their treatment because side effects were too bad. The number who competed their treatment was:
  • 82 people (76.6%) in the FCR group
  • 72 people (66.7%) in the FCM-R group

  Conclusion
  The trial team concluded that adding mitoxantrone to FCR (FCM-R) didn’t improve the response rate of chronic lymphocytic leukaemia in newly diagnosed people. FCR remained the best option for these people
  

• REC name

  Yorkshire & The Humber - Leeds West Research Ethics Committee

• REC reference

  08/H1307/135

• Date of REC Opinion

  9 Feb 2009

• REC opinion

  Further Information Favourable Opinion