AML 19: Adults with acute myeloid leukaemia or high-risk myelodysplastic syndrome
Myelodysplasic Syndromes / Posted 2 years ago
– For adults with AML or High Risk MDS aged 18 to 60 years, and for patients aged 60 years or over for whom intensive therapy is considered appropriate
If you are on the AML 19 trial, you will receive intensive induction chemotherapy like the patients who enter the AML 18 trial, following written consent to enter the study.
In this study, the first two courses of treatment, called the induction phase, will consist of two combinations of chemotherapy drugs which are being compared, called DA (Daunorubicin and Ara-C), or FLAG-Ida (Fludarabine, Ara-C, G-CSF and Idarubicin). Both combinations have been widely used and have already been extensively tested and given to hundreds of patients.
Again, similar to AML 18, this study will also compare if adding one or two doses of Mylotarg to standard treatment (DA or FLAG-Ida) is better. Therefore, patients will also receive one dose or two doses of Mylotarg with the first course of chemotherapy. This study will compare the treatments against each other to improve the outcomes for patients with AML.
Both combinations have been widely used before to treat AML and within the study, a comparison will be made comparing both groups of patients who received chemotherapy alone.
When remission is achieved in AML, there is still a risk the leukaemia can come back (known as relapse). To try to prevent this, more courses of chemotherapy will need to be given to kill off any leukaemia cells that got missed in the first treatment courses. This is called consolidation treatment. In consolidation, different treatments will be compared against each other with the aim of finding out which treatment is best at preventing relapse and for what patients.
Once the first course of chemotherapy has been completed, a bone marrow and blood test will be carried out to see how well the treatment has worked. Information about the risk of relapse, along with the bone marrow test results, will be discussed so that the next treatment course can go ahead. For some patients, a stem cell transplant will be advised, whilst for others this may not be necessary. This is quite a complicated decision which will be discussed when the time comes.
There are new methods of monitoring the disease, but we are not sure how useful they are and whether by using them the outcome of treatment will be improved. There will be an option to be in one group that will have extra bone marrow tests, but your doctor will discuss if it is appropriate for you to enter this part of the study.
At each stage of the study, usually at the end of each treatment, there will be information sheets available to explain the next steps and course of treatment. These options will be discussed with you and your haematology team.
This is a summary of the current AML clinical trials. These studies are constantly being amended when new therapies are available, in order to improve our treatments and patient outcomes.
Inclusion Criteria :
Patients are eligible for the AML19 trial if:
- They have one of the forms of acute myeloid 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 &gt;10% bone marrow blasts)
- Patients with acute promyelocytic leukaemia (APL) are eligible and should be entered into the randomisations specifically for APL (see Section 9).
- They are considered suitable for intensive chemotherapy.
@They should normally be 18 years up to the age of 60, but patients over this age are eligible if intensive therapy is considered a suitable option.
- The Serum creatinine should be ≤ 1.5 × ULN (upper limit of normal)
@Patients eligible for the Mylotarg randomisation must have Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤2.5 ×ULN and bilirubin ≤2.×ULN (Note: Patients who do not comply with the liver inclusion criteria are eligible to enter the trial but will be excluded from the Mylotarg randomisation)
- A negative pregnancy test within 2 weeks prior to trial entry in WOCBP to be repeated throughout the trial prior to each course of protocol treatment
- 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). Similarly women must agree to highly effective contraceptive measures (See Appendix J). This applies to APL and AML patients. In both males and females these measures must be in place for at least 30 days after the last administration of all IMPs.
- They have given written informed consent APL Patients:
- They have provided signed written informed consent (PIS 3)
- They have a morphological diagnosis of APL (if cytogenetic or molecular diagnosis is not confirmed patients will transfer to the non-APL treatments)
- They should be over 18 years.
- They have WHO performance status 0-2
- Their Serum total bilirubin is &lt; 2.0 mg/dL (≤51 µmol/L)
- Their Serum creatinine is &lt; 3.0 mg/dL (&lt; 260 µmol/L)
Exclusion Criteria :
Patients are not eligible for the AML arms of the AML19 trial if:
- 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.]
- They have received demethylation therapy for AML or high risk MDS defined as marrow blasts &gt;10%. Patients treated for lower risk MDS who progress to AML are eligible.
- They are in blast transformation of chronic myeloid leukaemia (CML).
- They have a concurrent active malignancy requiring treatment.
- They are pregnant or lactating.
- The physician and patient consider that intensive therapy is not an appropriate treatment option.
- Known infection with Human Immunodeficiency Virus (HIV).
- Patients with AST or ALT more than 2.5 times the local upper limit of normal or Bilirubin more than twice upper limit of normal, are not eligible for the Mylotarg randomisations. For Ganetespib randomisation there are specific cardiac exclusions:
- A myocardial infarction within 12 months
- Uncontrolled angina within 6 months
- Current or history of congestive heart failure New York Heart Association (NYHA) class 3 or 4, unless an echocardiogram (ECHO) or Multiple Gated Acquisition Scan (MUGA) performed either within 1 month prior to study screening or during screening results in a left ventricular ejection fraction (LVEF) that is ≥ 45% (or institutional lower limit of normal value).
- Diagnosed or suspected congenital long QT syndrome. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, torsades de pointes [TdP]) or any history of arrhythmia will be discussed with the Clinical Coordinator/Safety Physician prior to patient’s entry into the study.
- Prolonged QTcF interval on pre-entry ECG (≥450 ms)
- Any history of second or third degree heart block (may be eligible if the patient currently has a pacemaker
- Heart rate less than 50/minute on pre-entry ECG
- Uncontrolled hypertension
- Obligate need for a cardiac pacemaker
- Complete left bundle branch block
- Unstable Atrial fibrillation
- APL Patients: • They are aged less than 18 • They have an active malignancy requiring treatment at time of study entry • There is a lack of subsequent diagnostic confirmation of PML-RARA fusion at molecular level • Known infection with Human Immunodeficiency Virus (HIV). • Significant arrhythmias, ECG abnormalities or neuropathy are apparent • Severe uncontrolled pulmonary or cardiac disease is apparent. • They are pregnant or lactating
Study start date :
Study end date :
Wales-Based Study Contact :
Dr Steven Knapper
Principal Investigator :
Dr Steven Knapper