Trial to Test the Effects of Adding 1 of 2 New Treatment Agents to Commonly Used Chemotherapy Combinations (AML18)

January 22, 2020 updated by: Prof Nigel Russell, Cardiff University

A Trial for Older Patients With Acute Myeloid Leukaemia and High Risk Myelodysplastic Syndrome

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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:

  1. At diagnosis:

    For patients not known to have adverse risk cytogenetics DA chemotherapy plus a single dose of 3 mg/m2 of Mylotarg versus CPX-351. Patients with abnormal LFTs can enter the randomisation but receive DA alone or CPX-351.

  2. For patients who received DA chemotherapy but are not in CR or who are MRD +ve, or for whom MRD is not assessable.

    DA versus DAC versus FLAG-Ida

  3. All patients at second course who have received DA and have not received Vosaroxin and Decitabine induction AC220 versus no AC220 for a maximum of 3 cycles; then with or without maintenance for 1 year for patients allocated AC220
  4. For patients who are in CR or CRi and MRD -ve post course1 and have completed 2 courses of DA DA versus intermediate dose Cytarabine (IDAC)
  5. For patients who received CPX-351 chemotherapy but are not in CR or who are MRD +ve, or for whom MRD is not assessable CPX-351 100 units/m2 x 3 doses versus CPX-351 100 units/m2 x 2 doses

The trial will also assess:

  • Non-intensive allogeneic stem cell transplant for patients with matched sibling or matched unrelated donors.
  • The combination of Vosaroxin and Decitabine for those with known adverse risk cytogenetics at diagnosis

Study Type

Interventional

Enrollment (Anticipated)

1600

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Denmark
      • Aalborg, Denmark
        • Recruiting
        • Aalborg University Hospital
        • Contact:
          • Marianne Severinsen, MD
      • Aarhus, Denmark
        • Recruiting
        • Aarhus University Hospital
        • Contact:
          • Hans B Ommen, MD
      • Copenhagen, Denmark
        • Recruiting
        • Rigshospitalet
        • Contact:
          • Ulrik M Overgaard, MD
      • Copenhagen, Denmark
        • Recruiting
        • Herlev and Gentofte Hospital
        • Contact:
          • Claudia Schöllkopf, MD
      • Odense, Denmark
        • Recruiting
        • Odense University Hospital
        • Contact:
          • Duruta Weber, MD
      • Roskilde, Denmark
        • Recruiting
        • Roskilde Hospital
        • Contact:
          • Peter Møller
  • United Kingdom
      • Aberdeen, United Kingdom
        • Recruiting
        • Aberdeen Royal Infirmary
        • Contact:
          • Dominic Culligan, MD
      • Airdrie, United Kingdom
        • Recruiting
        • Monklands Hospital
        • Contact:
          • John Murphy, MD
      • Bangor, United Kingdom
        • Recruiting
        • Ysbyty Gwynedd Hospital
        • Contact:
          • Jim Seale, MD
      • Bath, United Kingdom
        • Recruiting
        • Royal United Hospital Bath
        • Contact:
          • Chris Knechtli, MD
      • Belfast, United Kingdom
        • Recruiting
        • Belfast City Hospital
        • Contact:
          • Mary McMullin, MD
      • Birmingham, United Kingdom
        • Recruiting
        • Queen Elizabeth Hospital
        • Contact:
          • Charles Craddock, DPhil
      • Birmingham, United Kingdom
        • Recruiting
        • Birmingham Heartland Hospital
        • Contact:
          • Manos Nikolousis, MD
      • Blackpool, United Kingdom
        • Recruiting
        • Blackpool Victoria Hospital
        • Contact:
          • Paul Cahalin, MD
      • Bodelwyddan, United Kingdom
        • Recruiting
        • Ysbyty Glan Clwyd
        • Contact:
          • Earnest Heartin, MD
      • Boston, United Kingdom
        • Recruiting
        • Pilgrim Hospital
        • Contact:
          • Charlotte Kallmeyer, MD
      • Bournemouth, United Kingdom
        • Recruiting
        • Royal Bournemouth General Hospital
        • Contact:
          • Joseph Chacko, MD
      • Bradford, United Kingdom
        • Recruiting
        • Bradford Royal Infirmary
        • Contact:
          • Sam Ackroyd, MD
      • Bristol, United Kingdom
        • Recruiting
        • Bristol Haematology & Oncology Centre
        • Contact:
          • Priyanka Mehta, MD
      • Cambridge, United Kingdom
        • Recruiting
        • Addenbrooke's Hospital
        • Contact:
          • Kiran Tawana, MD
      • Cardiff, United Kingdom
        • Recruiting
        • University Hospital of Wales
        • Contact:
          • Steve Knapper, MD
      • Cardiff, United Kingdom, CF14 4XN
        • Recruiting
        • UHW
        • Principal Investigator:
          • Steve Knapper
      • Cheltenham, United Kingdom
        • Recruiting
        • Cheltenham General Hospital
        • Contact:
          • Adam Rye, MD
      • Chester, United Kingdom
        • Recruiting
        • Countess of Chester Hospital
        • Contact:
          • Arvind Pillai, MD
      • Chichester, United Kingdom
        • Recruiting
        • St Richard's Hospital
        • Contact:
          • Santosh Narat, MD
      • Coventry, United Kingdom
        • Recruiting
        • University Hospital of Coventry and Warwickshire
        • Contact:
          • Beth Harris, MD
      • Derby, United Kingdom
        • Recruiting
        • Derby Teaching Hospital
        • Contact:
          • Ian Amott, MD
      • Dudley, United Kingdom
        • Recruiting
        • Russell Hall
        • Contact:
          • Rupert Hipkins, MD
      • Dundee, United Kingdom
        • Recruiting
        • Ninewells Hospital
        • Contact:
          • Sudhir Tauro, MD
      • Edinburgh, United Kingdom
        • Recruiting
        • Western General Hospital
        • Contact:
          • Peter Johnson, MD
      • Exeter, United Kingdom
        • Recruiting
        • Royal Devon & Exeter Hospital
        • Contact:
          • Jason Coppell, MD
      • Glasgow, United Kingdom
        • Recruiting
        • Beatson West of Scotland Cancer Centre
        • Contact:
          • Mhairi Copland, MD
      • Glasgow, United Kingdom
        • Recruiting
        • Hairmyres Hospital
        • Contact:
          • John Murphy, MD
      • Glasgow, United Kingdom
        • Recruiting
        • The New Victoria Hospital
        • Contact:
          • Gail Loud, MD
      • Gloucester, United Kingdom
        • Recruiting
        • Gloucestershire Royal Hospital
        • Contact:
          • Adam Rye, MD
      • Hamstead, United Kingdom
        • Recruiting
        • Royal Free Hospital
        • Contact:
          • Panagiotis Kottaridis, MD
      • Inverness, United Kingdom
        • Recruiting
        • Raigmore Hospital
        • Contact:
          • Caroline Duncan, MD
      • Ipswich, United Kingdom
        • Recruiting
        • Ipswich Hospital
        • Contact:
          • Mahesh Prahladan, MD
      • Irvine, United Kingdom
        • Recruiting
        • Crosshouse & Ayr Hospital
        • Contact:
          • William Gordon, MD
      • Kettering, United Kingdom
        • Recruiting
        • Kettering General Hospital
        • Contact:
          • Mark Kwan, MD
      • Kirkcaldy, United Kingdom
        • Recruiting
        • Victoria Hospital
        • Contact:
          • Victoria Campbell, MD
      • Larbert, United Kingdom
        • Recruiting
        • Forth Valley Royal Hospital
        • Contact:
          • Hugh Edwards, MD
      • Leeds, United Kingdom
        • Recruiting
        • St Jame's University Hospital
        • Contact:
          • Richard Kelly, MD
      • Leicester, United Kingdom
        • Recruiting
        • Leicester Royal Infirmary
        • Contact:
          • Katherine Hodgson, MD
      • Lincoln, United Kingdom
        • Recruiting
        • Lincoln County Hospital
        • Contact:
          • Charlotte Kallmeyer, MD
      • Liverpool, United Kingdom
        • Recruiting
        • Aintree University Hospital
        • Contact:
          • Vikram Singh, MD
      • Liverpool, United Kingdom
        • Recruiting
        • The Royal Liverpool University Hospital
        • Contact:
          • Amit Patel, MD
      • London, United Kingdom
        • Recruiting
        • University College London Hospital
        • Contact:
          • A Khwaja, MD
      • London, United Kingdom
        • Recruiting
        • Guy's Hospital
        • Contact:
          • Kavita Raj, MD
      • London, United Kingdom
        • Recruiting
        • St George's Hospital
        • Contact:
          • Matthias Klammer, MD
      • London, United Kingdom
        • Recruiting
        • St Bartholomew's Hospital
        • Contact:
          • Mathew Smith, MD
      • London, United Kingdom
        • Recruiting
        • The Royal Marsden
        • Contact:
          • David Taussig, M.D
      • Maidstone, United Kingdom
        • Recruiting
        • Maidstone District General Hospital
        • Contact:
          • Evangelia Dimitriadou, MD
      • Manchester, United Kingdom
        • Recruiting
        • Manchester Royal Infirmary
        • Contact:
          • Eleni Tholouli, MD
      • Manchester, United Kingdom
        • Recruiting
        • The Christie Hospital
        • Contact:
          • Mike Dennis, MD
      • Middlesbrough, United Kingdom
        • Recruiting
        • The James Cook University Hospital
        • Contact:
          • Ray Dang, MD
      • Milton Keynes, United Kingdom
        • Recruiting
        • Milton Keynes
        • Contact:
          • Moez Dungarwalla, MD
      • Newcastle, United Kingdom
        • Recruiting
        • Freeman Hospital
        • Contact:
          • Gail Jones, MD
      • Northampton, United Kingdom
        • Recruiting
        • Northampton General Hospital
        • Contact:
          • Jane Parker, MD
      • Norwich, United Kingdom
        • Recruiting
        • Norfolk & Norwich University
        • Contact:
          • Angela Collins, MD
      • Nottingham, United Kingdom
        • Recruiting
        • Nottingham University Hospital
        • Contact:
          • Nigel Russell, MD
      • Oldham, United Kingdom
        • Recruiting
        • Royal Oldham Hospital
        • Contact:
          • David Osborne, MD
      • Oxford, United Kingdom
        • Recruiting
        • Churchill Hospital
        • Contact:
          • Paresh Vyas, MD
      • Plymouth, United Kingdom
        • Recruiting
        • Derriford Hospital
        • Contact:
          • Patrick Medd, MD
      • Portsmouth, United Kingdom
        • Recruiting
        • Queen Alexandra Hospital
        • Contact:
          • Robert Corser, MD
      • Prescot, United Kingdom
        • Recruiting
        • Whiston Hospital & St Helens
        • Contact:
          • Toby Nicholson, MD
      • Romford, United Kingdom
        • Recruiting
        • Queen's Hospital
        • Contact:
          • Paul Greaves, MD
      • Salford, United Kingdom
        • Recruiting
        • Salford Royal Hospital
        • Contact:
          • Rowena Thomas-Dewing, MD
      • Salisbury, United Kingdom
        • Recruiting
        • Salisbury District Hospital
        • Contact:
          • Jonathan Cullis, MD
      • Slough, United Kingdom
        • Recruiting
        • Wexham Park Hospital
        • Contact:
          • Mark Offer, MD
      • Southampton, United Kingdom
        • Recruiting
        • Southampton General Hospital
        • Contact:
          • Deborah Richardon, MD
      • Stafford, United Kingdom
        • Recruiting
        • Stafford Hospital
        • Contact:
          • Paul Revell, MD
      • Stoke-on-Trent, United Kingdom
        • Recruiting
        • University Hospital of Royal Stoke
        • Contact:
          • Srivinas Pillai, MD
      • Sunderland, United Kingdom
        • Recruiting
        • Sunderland Royal Hospital
        • Contact:
          • Shikha Chattree, MD
      • Sutton, United Kingdom
        • Recruiting
        • St Helier Hospital
        • Contact:
          • Simon Stern, MD
      • Swansea, United Kingdom
        • Recruiting
        • Singleton Hospital
        • Contact:
          • Unmesh Monite, MD
      • Torquay, United Kingdom
        • Recruiting
        • Torbay District General Hospital
        • Contact:
          • Deborah Turner, MD
      • Truro, United Kingdom
        • Recruiting
        • Royal Cornwall Hospital
        • Contact:
          • Bryson Pottinger, MD
      • Uxbridge, United Kingdom
        • Recruiting
        • Hillingdon Hospital
        • Contact:
          • Richard Kaczmarski, MD
      • Wakefield, United Kingdom
        • Recruiting
        • Pinderfields Hospital
        • Contact:
          • Paul Moreton, MD
      • West Bromwich, United Kingdom
        • Recruiting
        • Sandwell Hospital
        • Contact:
          • Farooq Wandroo, MD
      • Wirral, United Kingdom
        • Recruiting
        • Arrowe Park Hospital
        • Contact:
          • Ranjit Dasgupta, MD
      • Wishaw, United Kingdom
        • Recruiting
        • Wishaw General Hospital
        • Contact:
          • John Murphy, MD
      • Wolverhampton, United Kingdom
        • Recruiting
        • New Cross Hospital
        • Contact:
          • Richard Whitmill, MD
      • Worcester, United Kingdom
        • Recruiting
        • Worcestershire Royal Hospital
        • Contact:
          • Nicholas Pemberton, MD
      • Worthing, United Kingdom
        • Recruiting
        • Worthing Hospital
        • Contact:
          • Santosh Narat, MD
      • York, United Kingdom
        • Recruiting
        • York Hospital
        • Contact:
          • Lee Bond, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Patients are eligible for the AML18 trial if:

  • 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) have received azacitidine are not eligible for the trial, but patients with <10% who have failed a hypomethylating agent and developed AML may enter the trial).
  • 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.
  • Patients entering the Vosaroxin/Decitabine arm must be over the age of 60 and have known adverse risk cytogenetics.
  • They have given written informed consent.
  • Serum creatinine ≤ 1.5 × ULN (upper limit of normal)
  • 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, the IMPs should be immediately stopped and the Trial Team should be contacted and pregnancy reporting procedures followed.
  • ECOG Performance Status of 0-2

Exclusion criteria

Patients are not eligible for the AML18 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 are in blast transformation of chronic myeloid leukaemia (CML)
  • They have a concurrent active malignancy excluding basal cell carcinoma
  • They are pregnant or lactating
  • They have Acute Promyelocytic Leukaemia
  • Known infection with human immunodeficiency virus (HIV)
  • Patients with prior cumulative anthracycline exposure (from prior treatment of a non AML cancer) of greater than 300 mg/m2 daunorubicin (or equivalent).
  • History of myocardial infarction (MI), unstable angina, cerebrovascular accident, or transient ischemic attack (CVA/TIA) within 3 months before entry

Specific exclusion criteria for the Mylotarg Arm

  • Pre-existing liver impairment with known cirrhosis
  • Total bilirubin > 1.5 x the upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) > 2.5 x ULN
  • Alanine aminotransferase (ALT) > 2.5 x ULN

Specific exclusion criteria for the Vosaroxin/Decitabine Entry

  • Total bilirubin > 1.5 x the upper limit of normal (ULN),
  • Aspartate aminotransferase (AST) > 2.5 x ULN
  • Alanine aminotransferase (ALT) > 2.5 x ULN
  • Left ventricular ejection fraction (LVEF) < 40% by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)]

Specific exclusion criteria for CPX-351 treatment

  • Hypersensitivity to cytarabine, daunorubicin or liposomal products
  • History of Wilson's disease or other copper-metabolism disorder

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm A

Patients not known adverse karyotype

Randomise between

Daunorubicin 60mg/m2 daily by i.v. infusion on days 1, 3 and 5 (3 doses) Cytosine Arabinoside 100mg/m2 12 hourly by i.v. push on days 1 - 10 inclusive (20 doses) Mylotarg (GO) 3mg/m2 on day 1 of DA chemotherapy

Versus

CPX-351 100 units/m2 on days 1, 3 and 5
Drug: Arm A Mylotarg plus DA Versus CPX-351
Patients not known to have adverse risk cytogenetics will enter a randomisation comparing DA with Mylotarg (GO) delivered at 3mg/m2 on day 1 of chemotherapy, with CPX-351 on days 1, 3 and 5.
Other Names:
  • CPX-351
  • Mylotarg (GO)
Active Comparator: Arm B

Patients with known adverse karyotype

5 cycles of Vosaroxin and Decitabine therapy
Drug: Arm B Vosaroxin and Decitabine
If a patient is known to have adverse risk Cytogenetics at diagnosis they will enter a registration to receive up to 5 courses of Vosaroxin and Decitabine.
Other Names:
  • Decitabine
  • Vosaroxin
Active Comparator: Arm C

Prior to Course 2 - Patients receving DA plus GO in course 1 and MRD positive PC1

Randomise between

Daunorubicin 50mg/2 daily by i.v. infusion on days 1, 3 and 5 (3 doses) Cytosine Arabinoside 100mg/m2 12 hourly by i.v.push on days 1 - 8 inclusive (16 doses)

Versus

Daunorubicin 50mg/m2 daily by i.v. infusion on days 1, 3 and 5 Cytosine Arabinoside 100mg/m2 12 hourly by i.v. push on days 1 - 8 inclusive Cladribine 5mg/m2 daily on days 1 - 5 inclusive

Versus Patients aged 60-69 Fludarabine 30mg/m2 daily on i.v. on days 2 - 6 inclusive Cytosine Arabinoside 1g/m2 daily over 4 hours Fludarabine on days 2 - 6 inclusive

Patients aged 70+ Fludarabine 25mg/m2 daily i.v. on days 2 - 5 inclusive Cytosine Arabinoside 1g/m2 daily over 4 hours Fludarabine on days 2 - 5 inclusive Idarubicin 5mg/m2 i.v. daily on days 3, 4 and 5 (3 doses)

And Randomisation to receive AC220 or not
Drug: Arm D Small molecule or Not
The randomisation to AC220 or not will take place immediately before course 2 of treatment for patients who have received DA induction +/- Mylotarg, irrespective of residual disease status. Patients allocated to receive AC220 will be randomised in a 1:1 fashion to AC220 or no small molecule with a 1:1 randomisation in patients drawing AC220 between short and long therapy.
Other Names:
  • No AC220
Drug: Arm C DA V FLAG-Ida V DAC
If a patient is not in CR or CRi after course 1 or is MRD +ve/unknown by flow cytometry they will be eligible to be randomised in a 1:1:1 fashion between DA, FLAG-Ida (or mini FLAG-Ida if 70 years or older) and DAC.
Other Names:
  • DAC
  • DA
  • FLAG-Ida
Active Comparator: Arm D

Prior to Course 2 - Patients that received DA plus GO in course 1 and MRD negative PC1

Randomisation to receive AC220 or not
Drug: Arm D Small molecule or Not
The randomisation to AC220 or not will take place immediately before course 2 of treatment for patients who have received DA induction +/- Mylotarg, irrespective of residual disease status. Patients allocated to receive AC220 will be randomised in a 1:1 fashion to AC220 or no small molecule with a 1:1 randomisation in patients drawing AC220 between short and long therapy.
Other Names:
  • No AC220
Active Comparator: Arm E

Prior to Course 2 for patients receiving CPX in course 1 and MRD positive PC1

Randomisation between

CPX-351 100 units/m2 on days 1, and 3 (CPX 200) versus CPX-351 100 units/m2 on days 1, 3 and 5 (CPX 300)
Drug: Arm E CPX-351 (200 V 300)
If a patient is not in CR or CRi after course 1 or is MRD +ve/unknown by flow cytometry they will be eligible to be randomised in a 1:1 fashion between CPX given on days 1, 3 and 5 (3 doses) and CPX given on days 1 and 3 (2 doses).
Other Names:
  • CPX-351
Active Comparator: Arm F

Prior to Course 3 - Patients that received DA plus GO in course 1 and MRD negative PC1

Randomise between Daunorubicin 50 mg/m2 daily by i.v. infusion on days 1 and 3 (2 doses) Cytosine Arabinoside 100 mg/m2 12-hourly by i.v. push on days 1 - 5 inclusive (10 doses)

versus

Intermediate dose Cytarabine (IDAC) schedule Cytosine Arabinoside 1g/m2 daily by 4 hour infusion on days 1- 5 inclusive (5 doses)
Drug: Arm F DA V IDAC
Following recovery from course 2, patients in the MRD-ve arm will be randomised between a further 5-day cycle of DA or a cycle of intermediate dose cytarabine (IDAC) as the third chemotherapy course.
Other Names:
  • DA
  • IDAC

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: 1 year
1 year
Complete remission (CR + CRi) achievement and reasons for failure (for induction questions)
Time Frame: 1 month
1 month
Duration of remission, relapse rates and deaths in first CR
Time Frame: 1 month
1 month
Toxicity, both haematological and non-haematological
Time Frame: 1 month
1 month
Supportive care requirements (and other aspects of health economics)
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
The relevance of the presence of a cytogenetic abnormality in the bone marrow of patients in morphological remission
Time Frame: At study end
At study end
The relevance of molecular characteristics and response to treatment
Time Frame: 1 month
1 month
To store diagnostic tissue for future research in the AML Tissue Bank
Time Frame: 6 years
6 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cardiff University

Collaborators

Cancer Research UK

Investigators

  • Principal Investigator: Nigel Russell, Prof, Nottingham University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 30, 2014

Primary Completion (Anticipated)

February 1, 2021

Study Completion (Anticipated)

February 1, 2022

Study Registration Dates

First Submitted

June 10, 2014

First Submitted That Met QC Criteria

October 22, 2014

First Posted (Estimate)

October 23, 2014

Study Record Updates

Last Update Posted (Actual)

January 23, 2020

Last Update Submitted That Met QC Criteria

January 22, 2020

Last Verified

August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AML18

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Myelodysplastic Syndrome

Clinical Trials on Arm A Mylotarg plus DA Versus CPX-351

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Romania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe