Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
1 Acute Myeloid Leukaemia 1.19 Gemtuzumab Ozogamicin (Mylotarg) - Clinical Trial AML17 Indication • Non APL Treatment, Induction chemotherapy, in combination with ADE or DA for Course 1 (ARM B, C, D&E of AML17 trial) Pre-treatment Evaluation • Morphology of blood and bone marrow aspirate. • Trephine biopsy and ‘roll preparations’ should be made if the aspirate is difficult • Immunophenotyping (including TdT, B & T markers, myeloid markers, cytoplasmic µ, surface Ig), preferably on bone marrow (BM) or peripheral blood (PB) blasts. 6ml bone marrow or 30ml peripheral blood in EDTA to be collected from trial patients and sent by courier to Haematology Department at Royal Free Hospital. • Cytochemistry: myeloperoxidase, PAS, acid phosphatase – note this may not be done routinely in some labs where immunophenotyping is readily available. • Trial patients should have 4ml bone marrow in tissue culture medium with preservative free heparin/ 30ml of heparinised blood sent to local lab for cytogenetic analysis. FISH analysis for common translocations and mono/trisomies may be useful. • Molecular analysis for relevant chimaeric genes, especially PML/RARA, BCR-ABL and (AML/ETO if available). Trial patients should have 4ml of bone marrow in culture medium, and 30ml heparinised blood sent to UCH. • Lumbar puncture (glucose, protein, microbiological culture, cytospin, gene rearrangement studies). This is not performed unless clinical suspicion of CNS disease. • Serological tests for: Hepatitis B & C, CMV, and HIV (with consent). • CXR. • ECG. • ECHO/ MUGA if cardiac history, elderly or previous history suggestive of potential cardiac disease (inc diabetes and hypertension) • Clotting screen. • FBC and blood film. • Renal/liver/bone panel, LDH, CRP, uric acid, serum glucose. • Liver function tests must be within twice the upper limit of the normal local range to be eligible for the Mylotarg randomisation. • Document WHO performance status of patient. • Document height, weight and body surface area, determine if Ideal Body Weight should be used. • Give adequate verbal and written information for patients and relatives concerning patient’s disease, treatment strategy and side effects. • Obtain written consent from patient or guardian. 1.19 Mylotarg (AML17) v1.0 Page 1 of 4 • • • • • • If appropriate, discuss the possibility of pregnancy with female patients of childbearing age and the need for contraception with both male and female patients. Women of child-bearing potential must have a negative pregnancy test within 2 weeks of trial entry. If appropriate, discuss potential risk of infertility with patient and relatives. Sperm banking if appropriate and time allows Patients allocated to receive Mylotarg must not have a white count greater than 30 x 109/L at the time of Mylotarg administration because of the risk of tumour lysis. Such patients should either have the WBC reduced with Hydroxycarbamide before commencing trial chemotherapy or have the administration of Mylotarg delayed until day 4 of the chemotherapy. Stop antihypertensive medication at least 12 hours pre-dose. Patients should not be given azole antifungal drugs until at least day 5 after the administration of Mylotarg. Hypotension may occur, withhold anti-hypertensive medications 12 hours before and 12 hours after treatment. Drug Regimen – ARM Day In combination with Drug Dose B 1 ADE Gemtuzumab 3mg/m 2 IV infusion in 100ml Sodium Chloride 0.9% over 2 hours C 1 ADE Gemtuzumab 6mg/m 2 IV infusion in 100ml Sodium Chloride 0.9% over 2 hours IV infusion in 100ml Sodium Chloride 0.9% over 2 hours IV infusion in 100ml Sodium Chloride 0.9% over 2 hours Administration Comments Adequate hydration needed. Maintain the urinary pH between 7 and 8, see considerations. Adequate hydration needed. Maintain the urinary pH between 7 and 8, see considerations. Adequate hydration needed. D 1 DA Gemtuzumab 3mg/m 2 E 1 DA Gemtuzumab 6mg/m 2 Maintain the urinary pH between 7 and 8, see considerations. Adequate hydration needed. Maintain the urinary pH between 7 and 8, see considerations. Considerations: • A separate IV line equipped with a low protein-binding 1.2-micron terminal filter must be used for administration of the drug. • The drug is light sensitive and must be protected from sunlight and unshielded fluorescent light during preparation and administration of the infusion. • Adequate hydration needed, if tumour lysis is expected. Add 50mmol Sodium Bicarbonate per litre of hydration fluid. Adjust the sodium bicarbonate dose to maintain the urinary pH between 7 and 8 (i.e. alkaline). 1.19 Mylotarg (AML17) v1.0 Page 2 of 4 For Anaphylaxis Interrupt infusion and administer: Hydrocortisone 100mg IV STAT, Chlorpheniramine 10mg IV STAT, Epinephrine (Adrenaline) 1:1000 - 0.5ml IM STAT Salbutamol 5mg Nebules for Inhalation Once signs and symptoms are completely resolved consider restarting or discontinuing treatment. Concurrent Medication • Adequate hydration, if tumour lysis is expected, add 50mmol Sodium Bicarbonate per litre hydration fluid. Adjust the sodium bicarbonate concentration to maintain the urinary pH between 7 and 8 (i.e. alkaline). Allopurinol should be given as soon as possible after diagnosis at a daily oral dose of 300mg daily (adjusted as above for renal failure) and continued until at least day 29 of the first phase of chemotherapy. Patients with high counts at diagnosis, LDH >1000, uric acid higher than normal, renal impairment or evidence of tumour lysis prior to treatment can be considered for treatment with Rasburicase to reduce the effect of tumour lysis. Anti-ulcer drug as per local policy. • Antimicrobial and antifungal prophylaxis as per local protocol. • Patients should not be given azole antifungal drugs until at least day 5 after the administration of Mylotarg. • Premedication, consisting of paracetamol and an antihistamine should be given before each infusion of mylotarg to reduce the incidence of a post-infusion symptom complex. Vital signs should be monitored during infusion and for four hours following infusion. • • Adverse effects • Mylotarg administration can result in severe hypersensitivity reactions (including anaphylaxis), and other infusion-related reactions which may include severe pulmonary events. Infrequently, hypersensitivity reactions and pulmonary events have been fatal. In most cases, infusion-related symptoms occurred during the infusion or within 24 hours of administration of Mylotarg and resolved. Mylotarg infusion should be interrupted for patients experiencing dyspnoea or clinically significant hypotension. Patients should be monitored until signs and symptoms completely resolve. Discontinuation of Mylotarg treatment should be strongly considered for patients who develop anaphylaxis, pulmonary oedema, or acute respiratory distress syndrome. Since patients with high peripheral blast counts may be at greater risk for pulmonary events and tumour lysis syndrome, the peripheral white count must be below 30,000/µL prior to administration of Mylotarg. 1.19 Mylotarg (AML17) v1.0 Page 3 of 4 • Hepatotoxicity, including severe hepatic veno-occlusive disease (VOD), has been reported in association with the use of Mylotarg as a single agent, as part of a combination chemotherapy regimen, and in patients without a history of liver disease. Patients with underlying hepatic disease or abnormal liver function, and patients receiving Mylotarg in combinations with other chemotherapy are at increased risk for developing VOD, including severe VOD. Patients should be carefully monitored for symptoms of hepatotoxicity, including rapid weight gain, right upper quadrant pain, hepatomegaly, ascites, and elevations in bilirubin and/or liver enzymes. • Hypotension may occur, withhold anti-hypertensive medications 12 hours before and 12 hours after treatment. • Tumor Lysis Syndrome: Tumor Lysis Syndrome may be a consequence of leukemia treatment with any anti-leukaemic agent including Mylotarg. Renal failure secondary to Tumor Lysis Syndrome has been reported in association with the use of Mylotarg. Appropriate measures, (e.g. hydration and allopurinol), must be taken to prevent hyperuricemia. References • • • • • AML 17 – MRC Protocol (May 2008) WLCN – Mylotarg protocol Product insert. NLCN Dosage Adjustment for Cytotoxics in Hepatic Impairment , November 2003 NLCN Dosage Adjustment for Cytotoxics in Renal Impairment , November 2003 Patient information • • • Leukaemia Research Fund - Adult Acute Myeloid Leukaemia booklet CancerBACUP - Acute myeloid leukaemia booklet Cancer BACUP fact file – patient drug information leaflets Written by: Nicki Panoskaltsis, Wendy Ng Authorised by: WLCN Haematology TWG Date for review by Haematology TWG: 1.19 Mylotarg (AML17) v1.0 Page 4 of 4