A trial for older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome
- Conditions
- CancerAcute myeloid leukaemia (AML) and high-risk myelodysplastic syndrome (MDS)Myeloid leukaemia
- Registration Number
- ISRCTN31682779
- Lead Sponsor
- Cardiff University (UK)
- Brief Summary
2023 Interim results article in https://pubmed.ncbi.nlm.nih.gov/37595359/ Fractionated versus single-dose gemtuzumab ozogamicin (added 21/08/2023)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 1935
Current participant inclusion criteria as of 22/02/2023:
1. They have one of the forms of acute myeloid leukaemia, (except Acute Promyelocytic Leukaemia) as defined by the WHO Classification (Appendix A). This can be any type of de novo AML (including patients with AML with morphological MRC who do not have a history of MDS or known MDS-related cytogenetics) or high risk Myelodysplastic Syndrome, defined as greater than 10% marrow blasts (RAEB-2). Patients with a prior history of a myeloproliferative neoplasm may be included provided they meet none of the exclusion criteria.
2. Patients should normally be over the age of 60 years, but patients under this age are eligible if they are not considered eligible for the MRC AML19 trial. Please contact the trial team for further information.
3. They have given written informed consent
4. Serum creatinine =1.5 × ULN (upper limit of normal)
5. Sexually mature males must agree to use an adequate and medically accepted method of contraception throughout the study if them or their sexual partners are women of childbearing potential (WOCBP). These measures must be in place for 6 months for patients receiving CPX-351 and 7 months (females) or 4 months (males) for Mylotarg – more comprehensive guidance is included in the current Summary of Product Characteristics (SPC) for these agents. Men should be advised to not father a child while receiving trial treatment. Similarly women must agree to adequate contraceptive measures and avoid becoming pregnant while on protocol treatment. In the event of pregnancy at any point during the trial, the IMPs should be immediately stopped and the Trial Team should be contacted and pregnancy reporting procedures followed
6. ECOG Performance Status of 0-2
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Previous participant inclusion criteria as of 02/10/2019:
1. They have one of the forms of acute myeloid leukaemia, except Acute Promyelocytic Leukaemia as defined by the WHO Classification (Appendix A) this can be any type of de novo or secondary AML – or high risk Myelodysplastic Syndrome, defined as greater than 10% marrow blasts (RAEB-2). (NB patients with prior MDS (>10% blasts, RAEB2) who have received prior azacitidine are not eligible for the trial, but patients with <10% who have failed a hypomethylating agent and developed AML may enter the trial)
2. Patients should normally be over the age of 60, but patients under this age are eligible if they are not considered eligible for the MRC AML19 trial. Please contact the trial team for further information.
3. Patients entering the vosaroxin/decitabine arm must be over the age of 60 and have known adverse risk cytogenetics at entry
4. They have given written informed consent
5. Serum creatinine = 1.5 × ULN (upper limit of normal)
6. Sexually mature males must agree to use an adequate and medically accepted method of contraception throughout the study if their sexual partners are women of child bearing potential (WOCBP). Men should be advised to not father a child while receiving trial treatment. Similarly women must agree to adequate contraceptive measures and avoid becoming pregnant while on protocol treatment. In both males and females these measures must be in place for at least 3 months following completion of Decitabine and at least 6 months after the last administration of Cladribine. The time period following treatment with Decitabine where it is safe to become pregnant is unknown. In the event of pregnancy at any point during the trial,
Current participant exclusion criteria as of 22/02/2023:
Patients are not eligible for the AML18 trial if:
1. Patients that are known to either have adverse risk cytogenetics as defined by Grimwade or cytogenetic changes that meet the WHO definition of AML-MRC
2. They have therapy–related AML (t-AML) with documented history of prior cytotoxic therapy or radiotherapy
3. They have a documented history of CMMoL prior to transformation to AML
4. They have a documented history of MDS prior to transformation AML
5. They have previously received cytotoxic chemotherapy for AML. (Hydroxycarbamide, or similar low-dose therapy, to control the white cell count prior to initiation of intensive therapy, is not an exclusion.
6. They are in blast transformation of chronic myeloid leukaemia (CML)
7. They have a concurrent active malignancy excluding basal cell carcinoma
8. They are pregnant or lactating
9. They have Acute Promyelocytic Leukaemia
10. Known infection with human immunodeficiency virus (HIV)
11. Patients with prior cumulative anthracycline exposure (from prior treatment of a non-AML cancer) of greater than 300 mg/m2 daunorubicin (or equivalent)
12. History of myocardial infarction (MI), unstable angina, cerebrovascular accident, or transient ischemic attack (CVA/TIA) within 3 months before entry
Mylotarg-specific exclusion criteria:
1. Pre-existing liver impairment with known cirrhosis
2. Total bilirubin >2.0 x the upper limit of normal (ULN)
3. Aspartate aminotransferase (AST) >2.5 x ULN
4. Alanine aminotransferase (ALT) >2.5 x ULN
CPX-351-specific exclusion criteria:
1. Hypersensitivity to cytarabine, daunorubicin or liposomal products
2. History of Wilson’s disease or other copper-metabolism disorder
In addition patients are not eligible for the AC220 randomisation if they have these cardiovascular system exclusion criteria:
1. Known serious cardiac illness or medical conditions, including but not limited to:
1.1. Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling temporary pacemaker
1.2. Ventricular tachycardia or a supraventricular tachycardia that requires treatment with a Class Ia antiarrhythmic drug (e.g., quinidine, procainamide, disopyramide) or Class III antiarrhythmic drug (e.g., sotalol, amiodarone, dofetilide). Use of other antiarrhythmic drugs is permitted.
1.3. Use of medications that have been linked to the occurrence of torsades de pointes
1.4. Second- or third-degree atrioventricular (AV) block unless treated with a permanent pacemaker
1.5. Complete left bundle branch block (LBBB)
1.6. History of long QT Syndrome or a family member with this condition
1.7. Serum potassium, magnesium, and calcium levels outside the laboratory’s reference range
1.8. QTc >450 ms (average of triplicate ECG recordings); a consistent method of QTc calculation must be used for each patient’s QTc measurements. QTcF (Fridericia’s formula) is preferred. Please see the trial website for QTcF calculator.
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Previous participant exclusion criteria as of 02/10/2019:
Patients are not eligible for the AML18 trial if:
1. They have previously received cytotoxic chemotherapy for AML [Hydroxycarbamide, or similar low-dose therapy, to control the white count prior to initiation of intensive therapy, is not an exclusion]
2. They are in blast transformation of chronic myeloid leukaemia (CML)
3.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method