Ignite Creation Date:
2024-05-06 @ 10:53 AM
Last Modification Date:
2024-10-26 @ 12:37 PM
Study NCT ID:
NCT03379727
Status:
COMPLETED
Last Update Posted:
2024-02-29
First Post:
2017-12-14
Brief Title:
Study to Assess the Safety and Efficacy of Midostaurin PKC412 in Combination With Standard Chemotherapy During Induction and Consolidation Followed by 12 Months of Maintenance Monotherapy in Patients With Newly-diagnosed FMS-like Tyrosine 3 FLT3 Kinase Receptor-mutated Acute Myeloid Leukemia
Sponsor:
Novartis Pharmaceuticals
Organization:
Novartis
Study Overview
Official Title:
An Open-label Multi-Center Phase IIIb Study to Assess the Safety and Efficacy of Midostaurin PKC412 in Patients 18 Years of Age or Older With Newly-diagnosed FLT3-mutated Acute Myeloid Leukemia Who Are Eligible for 73 or 52 Chemotherapy
Status:
COMPLETED
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 purpose of this study was to gather and evaluate additional safety and efficacy data on the combination of midostaurin and standard of care for adult patients with newly diagnosed Fms-like tyrosine kinase receptor FLT3 mutated Acute Myeloid Leukemia AML who were eligible for standard induction and consolidation
Detailed Description:
This Phase IIIb study was designed as a single arm study and allowed the assessment of variation of the 73 regimen in an extended patient population compared to RATIFY higher dose of daunorubicin 60-90 mgm2day the substitution of daunorubicin by idarubicin 12mgm2day and lower dose of cytarabine 100-200 mgm2day and the 52 reduced dose regimen Safety was the primary endpoint Complete Response CRComplete remission with incomplete hematological recovery CRi in induction consolidation and maintenance therapy was collected as secondary endpoint
Patients who were newly diagnosed with AML had a known FLT3 ITD Internal tandem duplication or TKD Tyrosine kinase domain mutation and had recently started on 73 or 52 in induction and high dose of cytarabine in consolidation were consented and screened for the clinical study
The protocol treatment allowed the following treatment phases
Induction Phase cytarabine with anthracycline idarubicin or daunorubicin sequentially per HCP choice followed by midostaurin on day 8 In the first Induction phase a bone marrow aspiration was performed in all subjects on Days 21- 28 according to local standard of care to determine the need for a second induction cycle If the marrow aspirate was inadequate to make a determination the bone marrow assessment was repeated within one week If the Day 21-28 according to local standard of care bone marrow aspiration reveals 5 leukemic blasts in a cellular marrow 20 a second induction was given For subjects requiring a second induction treatment began at least 3 days after completing midostaurin Bone marrow aspiration was performed within one week after recovery of ANC 1000μL and platelets 100000μL to assess for response Subjects in CR proceeded to consolidation therapy Subjects not achieving a marrow remission or with persistent blasts were to be removed from protocol therapy Subjects with CRi proceeded to consolidation therapy as per investigators discretion 1 or 2 cycles of 73 or 52 regimens switching between regimens was not allowed
Consolidation Phase for subjects in CRCRi after consolidation therapy up to four cycles of cytarabine consolidation per investigators discretion with midostaurin given sequentially during each cycle Based upon the superior results reported for AML subjects less than 60 years old with normal karyotypes in prospective clinical trials and RATIFY who achieved a CRCRi after induction received further therapy with midostaurin Subjects received up to four cycles of consolidation therapy Each consolidation cycle was four weeks in duration and was to begin within two weeks following hematologic recovery ANC 1000μL platelet count 100000μL but not sooner than 31 days from the beginning of the previous cycle A bone marrow aspiration was to be performed prior to the first consolidation cycle C1D1 and later could be performed if necessary per investigators decision at any time during Consolidation Phase
Maintenance Phase for subjects in CRCRi after consolidation therapy Subjects who continued in CRCRi by bone marrow aspiration and blood evaluation after four cycles of consolidation therapy received midostaurin Prior to maintenance therapy all significant acute toxicity from consolidation therapy was to be resolved to grade 2 Subjects with CRi proceeded to maintenance therapy as per investigators discretion and for CR subjects maintenance therapy began after hematologic recovery ANC 1000μL platelet count 100000μL from remission consolidation and at least 3 days after the last dose of midostaurin during consolidation Subjects who were unable to complete four courses of HiDAC consolidation because of toxicity could still be eligible for maintenance therapy at the discretion of the principal investigator after the last dose of consolidation after recovery from hematologic and other significant acute toxicity A bone marrow examination was to be performed prior to the first maintenance and every 3 months during Maintenance phase Maintenance phase was up to 12 cycles of maintenance therapy with single-agent midostaurin or until relapse unacceptable toxicity or death physicians decision subjectguardians decision protocol deviation study termination by sponsor lost to follow-up technical problems pregnancy subject withdrew consent or until the end of study whichever event occured first
Patients who were newly diagnosed with AML had a known FLT3 ITD Internal tandem duplication or TKD Tyrosine kinase domain mutation and had recently started on 73 or 52 in induction and high dose of cytarabine in consolidation were consented and screened for the clinical study
The protocol treatment allowed the following treatment phases
Induction Phase cytarabine with anthracycline idarubicin or daunorubicin sequentially per HCP choice followed by midostaurin on day 8 In the first Induction phase a bone marrow aspiration was performed in all subjects on Days 21- 28 according to local standard of care to determine the need for a second induction cycle If the marrow aspirate was inadequate to make a determination the bone marrow assessment was repeated within one week If the Day 21-28 according to local standard of care bone marrow aspiration reveals 5 leukemic blasts in a cellular marrow 20 a second induction was given For subjects requiring a second induction treatment began at least 3 days after completing midostaurin Bone marrow aspiration was performed within one week after recovery of ANC 1000μL and platelets 100000μL to assess for response Subjects in CR proceeded to consolidation therapy Subjects not achieving a marrow remission or with persistent blasts were to be removed from protocol therapy Subjects with CRi proceeded to consolidation therapy as per investigators discretion 1 or 2 cycles of 73 or 52 regimens switching between regimens was not allowed
Consolidation Phase for subjects in CRCRi after consolidation therapy up to four cycles of cytarabine consolidation per investigators discretion with midostaurin given sequentially during each cycle Based upon the superior results reported for AML subjects less than 60 years old with normal karyotypes in prospective clinical trials and RATIFY who achieved a CRCRi after induction received further therapy with midostaurin Subjects received up to four cycles of consolidation therapy Each consolidation cycle was four weeks in duration and was to begin within two weeks following hematologic recovery ANC 1000μL platelet count 100000μL but not sooner than 31 days from the beginning of the previous cycle A bone marrow aspiration was to be performed prior to the first consolidation cycle C1D1 and later could be performed if necessary per investigators decision at any time during Consolidation Phase
Maintenance Phase for subjects in CRCRi after consolidation therapy Subjects who continued in CRCRi by bone marrow aspiration and blood evaluation after four cycles of consolidation therapy received midostaurin Prior to maintenance therapy all significant acute toxicity from consolidation therapy was to be resolved to grade 2 Subjects with CRi proceeded to maintenance therapy as per investigators discretion and for CR subjects maintenance therapy began after hematologic recovery ANC 1000μL platelet count 100000μL from remission consolidation and at least 3 days after the last dose of midostaurin during consolidation Subjects who were unable to complete four courses of HiDAC consolidation because of toxicity could still be eligible for maintenance therapy at the discretion of the principal investigator after the last dose of consolidation after recovery from hematologic and other significant acute toxicity A bone marrow examination was to be performed prior to the first maintenance and every 3 months during Maintenance phase Maintenance phase was up to 12 cycles of maintenance therapy with single-agent midostaurin or until relapse unacceptable toxicity or death physicians decision subjectguardians decision protocol deviation study termination by sponsor lost to follow-up technical problems pregnancy subject withdrew consent or until the end of study whichever event occured first
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
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 |
|---|---|---|---|
| 2016-004440-12 | EUDRACT_NUMBER | None | None |