Ignite Creation Date:
2024-05-05 @ 7:22 PM
Last Modification Date:
2024-10-26 @ 9:47 AM
Study NCT ID:
NCT00651261
Status:
UNKNOWN
Last Update Posted:
2021-08-18
First Post:
2008-04-01
Brief Title:
Daunorubicin Cytarabine and Midostaurin in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
Sponsor:
Alliance for Clinical Trials in Oncology
Organization:
Alliance for Clinical Trials in Oncology
Study Overview
Official Title:
A Phase III Randomized Double-Blind Study of Induction DaunorubicinCytarabine and Consolidation High-Dose Cytarabine Chemotherapy Midostaurin PKC412 IND 101261 or Placebo in Newly Diagnosed Patients 60 Years of Age With FLT3 Mutated Acute Myeloid Leukemia AML
Status:
UNKNOWN
Status Verified Date:
2021-08
Last Known Status:
ACTIVE_NOT_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:
None
Brief Summary:
The purpose of this study is to compare the effects good andor bad of a standard chemotherapy regimen for AML that includes the drugs daunorubicin and cytarabine combined with or without midostaurin also known as PKC412 to find out which is better This research is being done because it is unknown whether the addition of midostaurin to chemotherapy treatment is better than chemotherapy treatment alone Midostaurin has been tested in over 400 patients and is being studied in a number of illnesses including AML colon cancer and lung cancer Midostaurin blocks an enzyme produced by a gene known as FLT3 that may have a role in the survival and growth of AML cells Not all leukemia cells will have the abnormal FLT3 gene This study will focus only on patients with leukemia cells with the abnormal FLT3 gene
Detailed Description:
In this study patients will receive either the experimental agent midostaurin or placebo combined with chemotherapy treatment Patients are stratified according to FLT3 mutation status internal tandem duplication ITD allelic ratio 07 vs ITD allelic ratio 07 vs tandem kinase domain TKD There are three parts to the study treatment remission induction therapy remission consolidation therapy and continuation therapy
Remission Induction Therapy
Cytarabine 200 mgm2day by continuous intravenous infusion on days 1-7
Daunorubicin 60 mgm2day by intravenous push or short infusion on days 1-3
Midostaurin 50 mg two 25 mg capsules or placebo for midostaurin 2 capsules twice a day by mouth on days 8-21
A bone marrow aspiration will be performed in all patients on Day 21 to determine the need for a second induction cycle
Remission Consolidation Four Remission Consolidation Cycles
High dose cytarabine 3000 mgm2 will be given by intravenous infusion over 3 hours every 12 hours on days 1 3 and 5 Serial neurologic evaluation will be performed before and following the infusion of high-dose cytarabine
Dexamethasone 01 or other corticosteroid ophthalmic solution 2 drops to each eye once daily to begin 6-12 hours prior to the initiation of the cytarabine infusion and to continue for at least 24 hours after the last cytarabine dose
Midostaurin 50 mg two 25 mg capsules or placebo for midostaurin 2 capsules twice a day by mouth on days 8-21
MidostaurinPlacebo Continuation Therapy
Midostaurin 50 mg two 25 mg capsules or placebo for midostaurin 2 capsules by mouth twice a day for 28 days Each cycle will be 28 days in length Continuation therapy with midostaurinplacebo will continue until relapse or for 12 cycles maximum
The primary and secondary objectives of this study are
Primary objective
To determine if the addition of midostaurin to daunorubicincytarabine induction high-dose cytarabine consolidation and continuation therapy improves overall survival OS in both the mutant FLT3-ITD and FLT3-TKD AML patients
Secondary objectives
To compare the overall survival OS in the two groups using an analysis in which patients who receive a stem cell transplant are censored at the time of transplant
To compare the complete response CR rate between the two treatment groups
To compare the event-free survival EFS between the two treatment groups
To compare the disease free survival DFS of the two treatment groups
To compare the disease free survival rate one year after completion of the continuation phase of the two groups
To assess the toxicity of the experimental combination
To describe the interaction between treatment outcome and pretreatment characteristics such as age performance status white blood cell WBC count morphology cytogenetics and molecular and pharmacodynamic features
To assess the population pharmacokinetics popPK of midostaurin and its two major metabolites CGP52421 and CGP62221 The potential associations between PK exposure and FLT3 status OS EFS and clinical response will be explored
There is a pharmacokinetic sub-study CALGB 60706 within CALGB 10603 This embedded companion study must be offered to all patients enrolled on CALGB 10603 although patients may opt not to participate in CALGB 60706
After study entry patients are followed periodically for up to 10 years
Remission Induction Therapy
Cytarabine 200 mgm2day by continuous intravenous infusion on days 1-7
Daunorubicin 60 mgm2day by intravenous push or short infusion on days 1-3
Midostaurin 50 mg two 25 mg capsules or placebo for midostaurin 2 capsules twice a day by mouth on days 8-21
A bone marrow aspiration will be performed in all patients on Day 21 to determine the need for a second induction cycle
Remission Consolidation Four Remission Consolidation Cycles
High dose cytarabine 3000 mgm2 will be given by intravenous infusion over 3 hours every 12 hours on days 1 3 and 5 Serial neurologic evaluation will be performed before and following the infusion of high-dose cytarabine
Dexamethasone 01 or other corticosteroid ophthalmic solution 2 drops to each eye once daily to begin 6-12 hours prior to the initiation of the cytarabine infusion and to continue for at least 24 hours after the last cytarabine dose
Midostaurin 50 mg two 25 mg capsules or placebo for midostaurin 2 capsules twice a day by mouth on days 8-21
MidostaurinPlacebo Continuation Therapy
Midostaurin 50 mg two 25 mg capsules or placebo for midostaurin 2 capsules by mouth twice a day for 28 days Each cycle will be 28 days in length Continuation therapy with midostaurinplacebo will continue until relapse or for 12 cycles maximum
The primary and secondary objectives of this study are
Primary objective
To determine if the addition of midostaurin to daunorubicincytarabine induction high-dose cytarabine consolidation and continuation therapy improves overall survival OS in both the mutant FLT3-ITD and FLT3-TKD AML patients
Secondary objectives
To compare the overall survival OS in the two groups using an analysis in which patients who receive a stem cell transplant are censored at the time of transplant
To compare the complete response CR rate between the two treatment groups
To compare the event-free survival EFS between the two treatment groups
To compare the disease free survival DFS of the two treatment groups
To compare the disease free survival rate one year after completion of the continuation phase of the two groups
To assess the toxicity of the experimental combination
To describe the interaction between treatment outcome and pretreatment characteristics such as age performance status white blood cell WBC count morphology cytogenetics and molecular and pharmacodynamic features
To assess the population pharmacokinetics popPK of midostaurin and its two major metabolites CGP52421 and CGP62221 The potential associations between PK exposure and FLT3 status OS EFS and clinical response will be explored
There is a pharmacokinetic sub-study CALGB 60706 within CALGB 10603 This embedded companion study must be offered to all patients enrolled on CALGB 10603 although patients may opt not to participate in CALGB 60706
After study entry patients are followed periodically for up to 10 years
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| CDR0000590404 | REGISTRY | Phyisician Data Query | None |
| CALGB-10603 | None | None | None |
| EUDRACT-2006-006852-37 | None | None | None |