Ignite Creation Date:
2024-05-06 @ 10:06 AM
Last Modification Date:
2024-10-26 @ 12:24 PM
Study NCT ID:
NCT03164057
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-05-29
First Post:
2017-05-19
Brief Title:
A Trial of Epigenetic Priming in Patients With Newly Diagnosed Acute Myeloid Leukemia
Sponsor:
St Jude Childrens Research Hospital
Organization:
St Jude Childrens Research Hospital
Study Overview
Official Title:
A Phase II Trial of Epigenetic Priming in Patients With Newly Diagnosed Acute Myeloid Leukemia
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-02
Last Known Status:
None
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:
None
Brief Summary:
The overall aim of this study is to determine if epigenetic priming with a DNA methyltransferase inhibitor DMTi prior to chemotherapy blocks is tolerable and carries evidence of a clinical efficacy signal as determined by minimal residual disease MRD event-free survival EFS and overall survival OS Tolerability for each of the agents as well as total reduction in DNA methylation and outcome assessments will be done to simultaneously obtain preliminary biological and clinical data for each DMTi in parallel
PRIMARY OBJECTIVES
Evaluate the tolerability of five days of epigenetic priming with azacitidine and decitabine as a single agent DMTi prior to standard AML chemotherapy blocks
Evaluate the change in genome-wide methylation burden induced by five days of epigenetic priming and the association of post-priming genome-wide methylation burden with event-free survival among pediatric AML patients
SECONDARY OBJECTIVES
Describe minimal residual disease levels following Induction I chemotherapy in patients that receive DMTi
Estimate the event-free survival and overall survival of patients receiving a DMTi prior to chemotherapy courses
PRIMARY OBJECTIVES
Evaluate the tolerability of five days of epigenetic priming with azacitidine and decitabine as a single agent DMTi prior to standard AML chemotherapy blocks
Evaluate the change in genome-wide methylation burden induced by five days of epigenetic priming and the association of post-priming genome-wide methylation burden with event-free survival among pediatric AML patients
SECONDARY OBJECTIVES
Describe minimal residual disease levels following Induction I chemotherapy in patients that receive DMTi
Estimate the event-free survival and overall survival of patients receiving a DMTi prior to chemotherapy courses
Detailed Description:
To determine tolerability priming with DMTi azacitidine or decitabine will be limited to Induction I and II during Part 1 of the study If DMTi treatment is tolerated during Part 1 the investigators will go on to an Expansion Phase Part 2 that includes DMTi priming prior to all chemotherapy blocks
Treatment will consist of 5 blocks of conventional chemotherapy Induction I Induction II Intensification I Intensification II and Intensification III over approximately 5 months
RANDOMIZATION Patients will be randomized to receive one of two DMTi azacitidine or decitabine for 5 days prior to Induction I Intrathecal ITHMA treatments will be given right before treatment on this study or on Day 1 of Induction I treatment Leucovorin will be given 24-30 hours following ITHMA
INDUCTION I CHEMOTHERAPY Patients receive cytarabine daunorubicin and etoposide
INDUCTION II CHEMOTHERAPY Patients receive their assigned DMTi for 5 days followed by fludarabine cytarabine G-CSF and idarubicin
Patients are then evaluated and assigned to either the low-risk arm intermediate-risk arm or the high-risk arm for Intensification therapy
Patients with 5 blasts following Induction II will be considered refractory and will go off therapy The rare high risk patient with an MRD 01 following Induction I may proceed directly to stem cell transplant SCT after Induction II - if a suitable donor is available and the transplant can be performed without delay MDS patients may proceed to SCT once they have achieved MRD 01 irrespective of the number of chemotherapy courses received
INTENSIFICATION I CHEMOTHERAPY - LOW-RISK AML INTERMEDIATE-RISK AML and HIGH-RISK AML with no donor Patients receive cytarabine and etoposide After administration of 5 days of a DMTi prior to Inductions I and II satisfies a tolerability determination criterion patients will also receive their randomly assigned DMTi for five days prior to cytarabine and etoposide
INTENSIFICATION II CHEMOTHERAPY - LOW RISK AML INTERMEDIATE-RISK AML and HIGH-RISK AML with no donor Patients receive mitoxantrone and cytarabine After administration of 5 days of a DMTi prior to Inductions I and II satisfies a tolerability determination criterion patients will also receive their randomly assigned DMTi for five days prior to mitoxantrone and cytarabine
INTENSIFICATION I CHEMOTHERAPY - HIGH-RISK AML with a donor Patients receive mitoxantrone and cytarabine followed by stem cell transplant SCT Treatment related AML patients and patients with treatment related MDS who have a donor but are not able to receive a SCT without delay will proceed to HR Intensification III and receive erwinia asparaginase and cytarabine After administration of 5 days of a DMTi prior to earlier courses satisfies a tolerability criterion patients will also receive their randomly assigned DMTi for five days prior to mitoxantrone and cytarabine or erwinia asparaginase and cytarabine
Treatment related AML patients and treatment related MDS patients that are not able to receive a SCT should go off treatment following Intensification II
INTENSIFICATION III CHEMOTHERAPY - INTERMEDIATE-RISK AML and HIGH-RISK AML with no donor Patients receive erwinia asparaginase and cytarabine After administration of 5 days of a DMTi prior to earlier courses satisfies a tolerability criterion patients will also receive their randomly assigned DMTi for five days prior to erwinia asparaginase and cytarabine
Treatment will consist of 5 blocks of conventional chemotherapy Induction I Induction II Intensification I Intensification II and Intensification III over approximately 5 months
RANDOMIZATION Patients will be randomized to receive one of two DMTi azacitidine or decitabine for 5 days prior to Induction I Intrathecal ITHMA treatments will be given right before treatment on this study or on Day 1 of Induction I treatment Leucovorin will be given 24-30 hours following ITHMA
INDUCTION I CHEMOTHERAPY Patients receive cytarabine daunorubicin and etoposide
INDUCTION II CHEMOTHERAPY Patients receive their assigned DMTi for 5 days followed by fludarabine cytarabine G-CSF and idarubicin
Patients are then evaluated and assigned to either the low-risk arm intermediate-risk arm or the high-risk arm for Intensification therapy
Patients with 5 blasts following Induction II will be considered refractory and will go off therapy The rare high risk patient with an MRD 01 following Induction I may proceed directly to stem cell transplant SCT after Induction II - if a suitable donor is available and the transplant can be performed without delay MDS patients may proceed to SCT once they have achieved MRD 01 irrespective of the number of chemotherapy courses received
INTENSIFICATION I CHEMOTHERAPY - LOW-RISK AML INTERMEDIATE-RISK AML and HIGH-RISK AML with no donor Patients receive cytarabine and etoposide After administration of 5 days of a DMTi prior to Inductions I and II satisfies a tolerability determination criterion patients will also receive their randomly assigned DMTi for five days prior to cytarabine and etoposide
INTENSIFICATION II CHEMOTHERAPY - LOW RISK AML INTERMEDIATE-RISK AML and HIGH-RISK AML with no donor Patients receive mitoxantrone and cytarabine After administration of 5 days of a DMTi prior to Inductions I and II satisfies a tolerability determination criterion patients will also receive their randomly assigned DMTi for five days prior to mitoxantrone and cytarabine
INTENSIFICATION I CHEMOTHERAPY - HIGH-RISK AML with a donor Patients receive mitoxantrone and cytarabine followed by stem cell transplant SCT Treatment related AML patients and patients with treatment related MDS who have a donor but are not able to receive a SCT without delay will proceed to HR Intensification III and receive erwinia asparaginase and cytarabine After administration of 5 days of a DMTi prior to earlier courses satisfies a tolerability criterion patients will also receive their randomly assigned DMTi for five days prior to mitoxantrone and cytarabine or erwinia asparaginase and cytarabine
Treatment related AML patients and treatment related MDS patients that are not able to receive a SCT should go off treatment following Intensification II
INTENSIFICATION III CHEMOTHERAPY - INTERMEDIATE-RISK AML and HIGH-RISK AML with no donor Patients receive erwinia asparaginase and cytarabine After administration of 5 days of a DMTi prior to earlier courses satisfies a tolerability criterion patients will also receive their randomly assigned DMTi for five days prior to erwinia asparaginase and cytarabine
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2017-00928 | REGISTRY | NCI Clinical Trial Registration Program | None |