Download 1 Acute Myeloid Leukaemia 1.19 Gemtuzumab Ozogamicin

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
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Morphology of blood and bone marrow aspirate.
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Trephine biopsy and ‘roll preparations’ should be made if the aspirate is difficult
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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.
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Cytochemistry: myeloperoxidase, PAS, acid phosphatase – note this may not be
done routinely in some labs where immunophenotyping is readily available.
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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.
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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.
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Lumbar puncture (glucose, protein, microbiological culture, cytospin, gene
rearrangement studies). This is not performed unless clinical suspicion of CNS
disease.
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Serological tests for: Hepatitis B & C, CMV, and HIV (with consent).
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CXR.
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ECG.
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ECHO/ MUGA if cardiac history, elderly or previous history suggestive of potential
cardiac disease (inc diabetes and hypertension)
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Clotting screen.
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FBC and blood film.
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Renal/liver/bone panel, LDH, CRP, uric acid, serum glucose.
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Liver function tests must be within twice the upper limit of the normal local range to
be eligible for the Mylotarg randomisation.
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Document WHO performance status of patient.
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Document height, weight and body surface area, determine if Ideal Body Weight
should be used.
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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
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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
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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
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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.
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Antimicrobial and antifungal prophylaxis as per local protocol.
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Patients should not be given azole antifungal drugs until at least day 5 after the
administration of Mylotarg.
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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.
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Adverse effects
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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
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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.
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Hypotension may occur, withhold anti-hypertensive medications 12 hours
before and 12 hours after treatment.
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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
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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
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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
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