Adults with Acute Myeloid Leukaemia or High-Risk Myelodysplastic Syndrome (... | Recruiting
Adults with Acute Myeloid Leukaemia... | Recruiting
Adults with Acute Myeloid Leukaemia or High-Risk Myelodysplastic Syndrome (AML19)
AML19

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Medical Conditions
  • Acute Myeloid Leukaemia High-Risk Myelodysplastic Syndrome
Primary Contact Details
Recruitment Status
Recruiting
Trial source and source ID number
ISRCTN78449203
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Summary
http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-different-treatments-for-acute-myeloid-leukaemia-and-high-risk-myelodysplastic
http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-treatment-for-acute-promyelocytic-leukaemia-aml-19
Research Details
  • For patients with acute myeloid leukaemia (AML) the aims of the AML19 trial are:
    1. To compare four induction chemotherapy schedules (namely DA + Mylotarg (3mg/m2) or DA + Mylotarg (3mg/m2 x2, maximum 5mg per day)versus FLAG-Ida + Mylotarg (3mg/m2) or FLAG-Ida + Mylotarg (3mg/m2 x2, maximum 5mg per day)) in patients who are not known at entry to have adverse cytogenetics
    2. For patients receiving FLAG-Ida to compare one or two courses of HDAC consolidation versus no further treatment
    3. Patients with FLT3 mutations may enter the AML19 pilot trial
    4. To assess the value of Ganetespib in patients who lack a FLT3 mutation and are not high risk
    5. In high risk patients, and those known to have adverse cytogenetics at entry, to compare novel treatment, CPX-351 vs FLAG-Ida
    6. In high risk patients who have received 2 courses of FLAG-Ida induction, to evaluate in a non randomised fashion the combination of Fludarabine + CPX-351
    7. In high risk patients, to evaluate, the value of allogeneic stem cell transplantation (SCT), from sibling or alternative donors
    8. To assess the clinical value of minimal residual disease monitoring for patients’ overall survival
    For patients with APL the aims of the AML19 trial are:
    1. To evaluate the Idarubicin based, AIDA Schedule
    2. Endpoints for Patients who have non-APL AML. The main endpoints for each comparison will be:
    2.1. Overall survival (OS)
    2.2. Complete remission (CR) achievement and reasons for failure (for induction questions)
    2.3. Duration of remission, relapse rates and deaths in first CR
    2.4. Toxicity, both haematological and non-haematological
    2.5. Quality of life for patients in the disease monitoring randomisation
    2.6. Supportive care requirements (and other aspects of health economics)
Phase
Phase III
Study Design
Randomised controlled open-label phase III trial, factorial design
Study Type
Interventional
Intervention

The AML19 trial looks to build upon previous trials in AML. It is known that the condition can present with one of two subtypes, and this is taken into account in the trial design.

In the majority of patients (those who do not have the APL-subtype), the trial looks to refine the current standard of care (which is a combination of drugs called DA) by asking a number of questions:
1. To compare two drug combinations (Daunorubicin/Ara-C – DA vs Fludarabine/Ara-C/G-CSF/Idarubicin – FLAG-Ida) to see which gives better survival
2. To identify the best way of giving the drug Mylotarg in addition to chemotherapy – either at a single dose of 3mg/m2 or in 2 doses of either 3mg/m2 or 5mg whichever is smaller. (This randomisation will only be available to patients who are suitable to receive Mylotarg).
3. In patients who receive FLAG-Ida, to work out the optimal number of courses of treatment. In particular, how much if any consolidation treatment with Ara-C is required – a randomisation between 0,1 and 2 courses of consolidation
4. To see if inhibiting a protein called HSP-90 with a drug called Ganetespib will improve outcomes
5. For poor risk patients, to see if a new drug called CPX-351 is any better than standard of care, which is FLAG-Ida
6. In patients who fail following 2 courses of FLAG-Ida (and so would not be suitable for further FLAG-Ida treatment) to evaluate a combination of Fludarabine and CPX-351
7. To evaluate whether a stem-cell transplant (e.g a bone marrow transplant) from either a matched sibling or unrelated donor can improve outcomes
8. To see whether monitoring patients bone marrow and blood sequentially can improve outcomes by successfully predicting patients who are likely to relapse, and what effect his has on quality of life.
Additionally patients who are found to have a FLT-3 mutation will be able to access the AML19 Pilot Trial of Ponatinib.

In patients with the APL subtype we will continue to assess the real-world effectiveness of standard of care, which is a combination of drugs called AIDA (ATRA plus Idarubicin), and to allow patients to access residual disease monitoring.

Intervention Type
Drug
Primary Outcome Measures
    To be assessed at the end of trial.
    The AML19 trial looks to build upon previous trials in AML. It is known that the condition can present with one of two subtypes, and this is taken into account in the trial design. In the majority of patients (those who do not have the APL-subtype), the trial looks to refine the current standard of care (which is a combination of drugs called DA) by asking a number of questions:
    1. To compare two drug combinations (Daunorubicin/Ara-C – DA vs Fludarabine/Ara-C/G-CSF/Idarubicin – FLAG-Ida) to see which gives better survival
    2. To identify the best way of giving the drug Mylotarg in addition to chemotherapy – either at a single dose of 3mg/m2 or in 2 doses of either 3mg/m2 or 5mg whichever is smaller. (This randomisation will only be available to patients who are suitable to receive Mylotarg).
    3. In patients who receive FLAG-Ida, to work out the optimal number of courses of treatment. In particular, how much if any consolidation treatment with Ara-C is required – a randomisation between 0,1 and 2 courses of consolidation
    4. To see if inhibiting a protein called HSP-90 with a drug called Ganetespib will improve outcomes
    5. For poor risk patients, to see if a new drug called CPX-351 is any better than standard of care, which is FLAG-Ida
    6. In patients who fail following 2 courses of FLAG-Ida (and so would not be suitable for further FLAG-Ida treatment) to evaluate a combination of Fludarabine and CPX-351
    7. To evaluate whether a stem-cell transplant (e.g a bone marrow transplant) from either a matched sibling or unrelated donor can improve outcomes
    8. To see whether monitoring patients bone marrow and blood sequentially can improve outcomes by successfully predicting patients who are likely to relapse, and what effect his has on quality of life.
    Additionally patients who are found to have a FLT-3 mutation will be able to access the AML19 Pilot Trial of Ponatinib. In patients with the APL subtype we will continue to assess the real-world effectiveness of standard of care, which is a combination of drugs called AIDA (ATRA plus Idarubicin), and to allow patients to access residual disease monitoring.
Secondary Outcome Measures
    To be reviewed at the end of the trial.
    In addition to the main clinical questions above, the trial will collect a lot of data on a well characterised group of patients. This will enable the following questions to be addressed:
    1. What is the relevance of detecting minimal residual disease using one of two methods (molecular and immunophenotypic)
    2. Are there biomarkers or other molecular (laboratory) measurements that correlate with clinical outcome
    Consent will be taken to store any excess diagnostic material for future research that will inform future trials.
Publication(s)
Sorry, this information is not available
Result Reports
Sorry, this information is not available
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Gender
Both
Age Range
Adult
Who Can Participate
Patient
Number of Participants
3000
Participant Inclusion Criteria
    AML Patients:
    1. 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 >10% bone marrow blasts)
    2. Patients with acute promyelocytic leukaemia (APL) are eligible and should be entered into the randomisations specifically for APL (see Section 9)
    3. They are considered suitable for intensive chemotherapy
    4. 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
    5. The serum creatinine should be ≤ 1.5 × ULN (upper limit of normal)
    6. 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)
    7. 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 adequate contraceptive measures. 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 ganetespib
    8. They have given written informed consent
    APL Patients:
    1. They have provided signed written informed consent (PIS 3)
    2. They have a morphological diagnosis of APL (if cytogenetic or molecular diagnosis is not confirmed patients will transfer to the non-APL treatments)
    3. They should be over 18 years
    4. They have WHO performance status 0-2
    5. Their serum total bilirubin is < 2.0 mg/dL (≤51 µmol/L)
    6. Their serum creatinine is < 3.0 mg/dL (< 260 µmol/L)
Participant Exclusion Criteria
    Patients are not eligible for the AML arms of the AML19 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 have received demethylation therapy for AML or high risk MDS defined as marrow blasts >10%. Patients treated for lower risk MDS who progress to AML are eligible
    3. They are in blast transformation of chronic myeloid leukaemia (CML)
    4. They have a concurrent active malignancy requiring treatment
    5. They are pregnant or lactating
    6. The physician and patient consider that intensive therapy is not an appropriate treatment option
    7. Known infection with Human Immunodeficiency Virus (HIV)
    8. 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:
    1. A myocardial infarction within 12 months
    2. Uncontrolled angina within 6 months
    3. 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)
    4. 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
    5. Prolonged QTcF interval on pre-entry ECG (≥450 ms)
    6. Any history of second or third degree heart block (may be eligible if the patient currently has a pacemaker
    7. Heart rate < 50/minute on pre-entry ECG
    8. Uncontrolled hypertension
    9. Obligate need for a cardiac pacemaker
    10. Complete left bundle branch block
    11. Atrial fibrillation
    APL Patients:
    1. They are aged < 18
    2. They have an active malignancy requiring treatment at time of study entry
    3. There is a lack of subsequent diagnostic confirmation of PML-RARA fusion at molecular level
    4. Known infection with Human Immunodeficiency Virus (HIV)
    5. Significant arrhythmias, ECG abnormalities or neuropathy are apparent
    6. Severe uncontrolled pulmonary or cardiac disease is apparent
    7. They are pregnant or lactating
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Trial Location(s)
Nottingham
Nottinghamshire
NG5 1PB
Trial Contact(s)
Primary Trial Contact
Prof Nigel Russell
-
Other Trial Contacts
Sorry, this information is not available
Countries Recruiting
United Kingdom
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Scientific Title
Adults with Acute Myeloid Leukaemia or High-Risk Myelodysplastic Syndrome (AML19): a randomised, controlled, open label Phase III trial
EudraCT Number
2014-002195-90
Funder(s)
  • Cancer Research UK
Other Study ID Numbers
SPON1334-04
Sponsor(s)
Cardiff University (UK)
Key Dates

Recruitment Start Date

01 Jan 2015

Recruitment End Date

01 Jan 2021

Trial Start Date

01 Jan 2015

Trial End Date

01 Jan 2021

Date added to source

08 Dec 2014

Date updated in source

27 Apr 2016