4.05 Protocol name: Alemtuzumab (MabCampath ), intravenous

Transcription

1 4.05 Protocol name: (MabCampath ), intravenous Indication Treatment of CLL refractory to fludarabine (either primary i.e. 17p deletion, or secondary i.e. following previous fludarabine treatment), without bulky disease Pre-treatment Evaluation Document histological sub-type of lymphoproliferative disorder according to WHO Classification. Document FBC (with film), U&E, creatinine, LFTs, calcium, glucose, serum protein electrophoresis, immunoglobulin levels a direct antiglobulin test (DAT). If staging is relevant this should include documentation of B symptoms, CT of chest, abdomen & pelvis bone marrow aspirate & trephine. Document WHO performance status of patient. Document height, weight body surface area. Consider ECG ± echocardiogram if clinical suspicion of cardiac dysfunction. Give adequate verbal written information for patients relatives concerning patient s disease, treatment strategy side effects. Obtain written consent from patient or guardian. If appropriate, discuss the possibility of pregnancy with female patients of child-bearing age the need for contraception with both male female patients. If appropriate, discuss potential risk of infertility with patient relatives. Consider intravenous hydration in patients with bulk disease. Allopurinol should be given for the first month of treatment All cellular blood components should be irradiated to prevent the rare occurrence of transfusion associated graft versus host disease Version 2.1.doc Page 1 of 5

2 Drug Regimen (OPCS code: X71.5) If each dose is well tolerated (i.e. < grade 2 acute, infusion-related toxicities) escalate doses as below Day Drug Dose Comments Initiation dose (week 1): 1 3mg If grade 3 adverse events occur (hypotension, rigors, fever or bronchospasm) at 3mg dose repeat 3mg dose daily until it is well tolerated with premedication as below, then escalate to 10mg. 2 10mg If grade 3 adverse events occur at 10mg dose repeat 10mg dose daily until it is well tolerated with pre-medication as below, then escalate to 30mg. 3 30mg Maintenance dose (week 2 onwards, weekly, up to 12 weeks) 3 times a week 30mg Pre-medication required 30 minutes before each dose: - Paracetamol 1g PO - Chlorphenamine 10mg IV or 4mg PO - may add hydrocortisone 100mg IV if needed 4.05 Version 2.1.doc Page 2 of 5

3 Drug Route Administration Comments Patient monitoring IV In 100ml Sodium chloride 0.9% or Dextrose 5% Over 2 hours* (* Infusionrelated reactions may be reduced by prolonging the infusion time) Inject required volume of 30mg/ml alemtuzumab solution through low-protein-binding 5 micron filter into the diluent bag use within 8 hours. For 1 st dose at each dose increase: - measure blood pressure pulse every 15 minutes for the 2 hours of infusion, then as clinically indicated. - monitor temperature before during infusion, as frequently as indicated - during escalation phase monitor for at least 4 hours post each infusion, or until side effects completely resolved Dose Modifications Haematological toxicity: Toxicity (grade or 10 9 /l) 1 st Occurrence 2 nd Occurrence 3 rd Occurrence Platelets <25 Neutrophils <0.5 Hold; restart at full dose (30mg) when recovered to Platelets >50 Neutrophils >1.0 Hold; restart at reduced dose (10mg) when recovered to Platelets >50 Neutrophils >1.0 Discontinue permanently May use G-CSF to support neutrophil count. Infection: - If serious infection develops during therapy, stop alemtuzumab until complete resolution. - May reinstitute alemtuzumab at the previous dose. - May give prophylactic therapy to prevent recurrence of the diagnosed infection, if clinically indicated Version 2.1.doc Page 3 of 5

4 Investigations prior to subsequent cycles FBC differential at least once a week Full response assessment every 4 weeks (including BM) CMV analysis once a week. If positive, confirm with PCR. If confirmed CMV infection, stop alemtuzumab treat with ganciclovir or foscarnet (seek specialist advice from Infectious Diseases Specialists). Monitor response to treatment Treatment Duration To maximal response up to 12 weeks for induction period If complete remission (CR), stop alemtuzumab continue to monitor patient without therapy If no leukaemia/tumour reduction or improvement in disease-related symptoms between week 4 week 8 evaluation, stop alemtuzumab continue to monitor patient. Restart therapy if criteria for progressive disease are fulfilled /or other need of further treatment. If evidence of disease progression, serious infection or unacceptable toxicity, discontinue alemtuzumab. Re-institution of - Use gradual dose escalation as above to avoid acute infusion-related adverse events. - Monitor patients continuously with a full assessment of response after 4 8 weeks of therapy. - Maximum treatment period after reinstitution is 8 weeks. - May be reinstituted several times for 4 to 8 weeks of treatment, as above, until disease becomes resistant or unresponsive to alemtuzumab. Concurrent Medication Oral systemic PCP prophylaxis should be given according to local protocol; start with the first course continue for at least 2 months after treatment is discontinued. Pentamidine may be used as an alternative. Allopurinol 300mg od PO (100mg if creatinine clearance <20mls/min) for D1 to D28 if WBC high, or bulky disease 4.05 Version 2.1.doc Page 4 of 5

5 ** Issue patient with DOH/National Blood Service Irradiated Blood Products information sheet: ** References SPC Patient Information bodies/ Written by: DrG. Abrahamson, P. McCalla & Dr S. Wagner Revised by: Sasha Marks, Stephanie Kirschke, September 2009 Authorised by: WLCN Haematology TWG, Date Date for review by Haematology TWG: xxx 4.05 Version 2.1.doc Page 5 of 5