Ignite Creation Date:
2024-05-06 @ 3:22 AM
Last Modification Date:
2024-10-26 @ 11:32 AM
Study NCT ID:
NCT02272478
Status:
UNKNOWN
Last Update Posted:
2020-01-23
First Post:
2014-06-10
Brief Title:
Trial to Test the Effects of Adding 1 of 2 New Treatment Agents to Commonly Used Chemotherapy Combinations
Sponsor:
Cardiff University
Organization:
Cardiff University
Study Overview
Official Title:
A Trial for Older Patients With Acute Myeloid Leukaemia and High Risk Myelodysplastic Syndrome
Status:
UNKNOWN
Status Verified Date:
2019-08
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
AML18
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 DaunorubicinAra-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 favourableintermediateadverse 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
At entry a randomisation will compare a standard chemotherapy schedule DA DaunorubicinAra-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 favourableintermediateadverse 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
Detailed Description:
AML18 is a trial primarily for older patients with AML and high risk Myelodysplastic Syndrome MDS It offers a randomised controlled Phase IIIII 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 mgm2 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 unitsm2 x 3 doses versus CPX-351 100 unitsm2 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
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 mgm2 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 unitsm2 x 3 doses versus CPX-351 100 unitsm2 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None