Trial to Test the Effects of Adding 1 of 2 New Treatment Agents to Commonly Used Chemotherapy Combinations (AML18)
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ClinicalTrials.gov Identifier: NCT02272478 |
Recruitment Status : Unknown
Verified August 2019 by Prof Nigel Russell, Cardiff University.
Recruitment status was: Recruiting
First Posted : October 23, 2014
Last Update Posted : January 23, 2020
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Tracking Information | ||||
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First Submitted Date ICMJE | June 10, 2014 | |||
First Posted Date ICMJE | October 23, 2014 | |||
Last Update Posted Date | January 23, 2020 | |||
Actual Study Start Date ICMJE | October 30, 2014 | |||
Estimated Primary Completion Date | February 2021 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | |||
Change History | ||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | |||
Current Other Pre-specified Outcome Measures | Not Provided | |||
Original Other Pre-specified Outcome Measures | Not Provided | |||
Descriptive Information | ||||
Brief Title ICMJE | Trial to Test the Effects of Adding 1 of 2 New Treatment Agents to Commonly Used Chemotherapy Combinations | |||
Official Title ICMJE | A Trial for Older Patients With Acute Myeloid Leukaemia and High Risk Myelodysplastic Syndrome | |||
Brief Summary | The AML18 Trial will evaluate several relevant therapeutic questions in Acute Myeloid Leukaemia (AML), as defined by the WHO, and High Risk Myelodysplastic Syndrome. The trial is primarily designed for patients over 60 years considered fit for an intensive chemotherapeutic approach, but younger patients who may not be considered suitable for the concurrent NCRI AML Trial for younger patients may also enter. Patients for whom intensive chemotherapy is not thought suitable may enter the concurrent NCRI trial of less intensive therapy (LI1). Approximately 1600 patients will be recruited. At entry, a randomisation will compare a standard chemotherapy schedule DA (Daunorubicin/Ara-C) combined with 1 dose of Mylotarg (gemtuzumab ozogamicin, or GO) in course 1 against CPX-351. Patients who have known adverse risk cytogenetics (using Grimwade 2010 classification favourable/intermediate/adverse) at diagnosis may enter a Phase 2 evaluation of the combination of Vosaroxin plus Decitabine. Patients who achieve complete remission (CR) and who are MRD negative by flow cytometry after course one of DA will receive one further course of DA, with a randomisation to receive, either a course of DA or intermediate dose Cytarabine (IDAC) as a third course. Patients who are MRD negative by flow cytometry after course one of CPX-351 will receive up to 2 further course of CPX. Patients who fail to achieve a CR after course 1 of DA or who are MRD positive by flow cytometry or for whom MRD information is not available, are eligible to be randomised to compare DA with DA plus Cladribine (DAC) or FLAG-Ida for up to two courses of therapy. Patients who fail to achieve a CR after course 1 of CPX-351 or who are MRD positive by flow cytometry or for whom MRD information is not available are eligible to be randomised between a second course of standard dose CPX versus a repeat of the course 1 schedule. Patients receiving Vosaroxin and Decitabine are excluded from these post course 1 randomisations . Following the outcome of course 1, patients who received DA chemotherapy on course 1 will be randomised to receive further chemotherapy with the 2nd generation FLT3 inhibitor AC220. Patients randomised to AC220 will be allocated a maximum of 3 courses (short AC220) or 3 courses plus maintenance for 1 year (long AC220). Patients receiving Vosaroxin and Decitabine are excluded from this randomisation. Patients will be eligible for a non-intensive allogeneic stem cell transplant if a suitable HLA matched donor is available. |
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Detailed Description | AML18 is a trial primarily for older patients with AML and high risk Myelodysplastic Syndrome (MDS). It offers a randomised controlled Phase II/III trial which uses a factorial design for maximum efficiency to evaluate two induction options followed by treatment with small molecule beyond course 1, and dose intensification for patients without evidence of MRD negativity. There are five randomised comparisons within the trial:
The trial will also assess:
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Study Type ICMJE | Interventional | |||
Study Phase ICMJE | Phase 2 Phase 3 |
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Study Design ICMJE | Allocation: Randomized Intervention Model: Factorial Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | |||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Unknown status | |||
Estimated Enrollment ICMJE |
1600 | |||
Original Estimated Enrollment ICMJE | Same as current | |||
Estimated Study Completion Date ICMJE | February 2022 | |||
Estimated Primary Completion Date | February 2021 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE | Inclusion Criteria Patients are eligible for the AML18 trial if:
Exclusion criteria Patients are not eligible for the AML18 trial if:
Specific exclusion criteria for the Mylotarg Arm
Specific exclusion criteria for the Vosaroxin/Decitabine Entry
Specific exclusion criteria for CPX-351 treatment
Specific exclusion criteria for Cladribine • Patient's serum creatinine must be within the local ULN to enter the randomisation. Patients for whom this is not the case can be randomised between the remaining options. In addition patients are not eligible for the AC220 randomisation if they have: Cardiovascular System Exclusion Criteria: Known serious cardiac illness or medical conditions, including but not limited to: I. Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling temporary pacemaker II. 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. III. Use of medications that have been linked to the occurrence of torsades de pointes (see Appendix for the list of such medications) IV. Second- or third-degree atrioventricular (AV) block unless treated with a permanent pacemaker V. Complete left bundle branch block (LBBB) VI. History of long QT Syndrome or a family member with this condition VII. Serum potassium, magnesium, and calcium levels not outside the laboratory's reference range VIII. 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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Sex/Gender ICMJE |
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Ages ICMJE | 60 Years and older (Adult, Older Adult) | |||
Accepts Healthy Volunteers ICMJE | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | Denmark, United Kingdom | |||
Removed Location Countries | ||||
Administrative Information | ||||
NCT Number ICMJE | NCT02272478 | |||
Other Study ID Numbers ICMJE | AML18 | |||
Has Data Monitoring Committee | Yes | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement ICMJE | Not Provided | |||
Current Responsible Party | Prof Nigel Russell, Cardiff University | |||
Original Responsible Party | Same as current | |||
Current Study Sponsor ICMJE | Cardiff University | |||
Original Study Sponsor ICMJE | Same as current | |||
Collaborators ICMJE | Cancer Research UK | |||
Investigators ICMJE |
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PRS Account | Cardiff University | |||
Verification Date | August 2019 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |