ADMIRE

Does the Addition of Mitoxantrone Improve Response to FCR chemotherapy in patients with CLL: A randomised Phase II Trial of fludarabine, cyclophosphamide and rituximab (FCR) with or without mitoxantrone (M) in previously untreated chronic lymphocytic leukaemia

· At least 18 years old.

· B-CLL with a characteristic immunophenotype.

· Binet’s Stages B, C or Progressive Stage A

· Requiring therapy by the IWCLL criteria in that they must have at least one of the following:

1. Evidence of progressive marrow failure as manifested by the development of, or worsening of, anaemia and/or thrombocytopenia.

2. Massive (ie, 6 cm below the left costal margin) or progressive or symptomatic splenomegaly

3. Massive nodes (ie, 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy.

4. Progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time (LDT) of less than 6 months as long as the lymphocyte count is over 30x10⁹/L

5. A minimum of any one of the following disease-related symptoms must be present:

(a) Unintentional weight loss more than or equal to 10% within the previous 6 months.

(b) Significant fatigue (ie, Eastern Cooperative Oncology Group PS 2 or worse; cannot work or unable to perform usual activities)

(c) Fevers of greater than 38.0°C for 2 or more weeks without other evidence of infection.

(d) Night sweats for more than 1 month without evidence of infection.

· No prior therapy for CLL.

· World Health Organisation (WHO) performance status (PS) of 0, 1 or 2

· Able to provide written informed consent

• Prior therapy for CLL

• Active infection.

• Past history of anaphylaxis following exposure to rat or mouse derived CDR-grafted humanised monoclonal antibodies.

• Pregnancy, lactation or women of child-bearing potential unwilling to use medically approved contraception whilst receiving treatment.

• Men whose partners are capable of having children but who are not willing to use appropriate medically approved contraception during the study, unless they are surgically sterile.

• CNS involvement with CLL.

• Mantle cell lymphoma.

• Symptomatic cardiac failure not controlled by therapy or unstable angina not adequately controlled by current therapy (in patients with a significant cardiac history the left ventricular function should be assessed and patients with severe impairment should be excluded)

• Other severe, concurrent diseases or mental disorders.

• Known HIV positive

• Patient has active or prior Hepatitis B or C

• Active secondary malignancy excluding basal cell carcinoma.

• Persisting severe pancytopenia (neutrophils <0.5 x 10⁹/l or platelets <50 x 10⁹/l) or transfusion dependent anaemia unless due to direct marrow infiltration by CLL

• Active haemolysis (patients with haemolysis controlled with prednisolone at a dose 10mg or less per day can be entered into the trial)

• Patients with a creatinine clearance of less than 30ml/min (either measured or derived by the Cockcroft formula )

Research Nurse

Alex Stichler

Tel 01132068577

Email alex.stichler@leedsth.nhs.uk

Principal Investigator

Dr Hillmen

Tel 01132068513

Email peter.hillmen@nhs.net

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