Ignite Creation Date:
2024-05-06 @ 11:44 AM
Last Modification Date:
2024-10-26 @ 12:49 PM
Study NCT ID:
NCT03591510
Status:
RECRUITING
Last Update Posted:
2024-04-05
First Post:
2018-06-25
Brief Title:
A Global Study of Midostaurin in Combination With Chemotherapy to Evaluate Safety Efficacy and Pharmacokinetics in Newly Diagnosed Pediatric Patients With FLT3 Mutated AML
Sponsor:
Novartis Pharmaceuticals
Organization:
Novartis
Study Overview
Official Title:
A Phase II Open-label Single Arm Study to Evaluate the Safety Efficacy and Pharmacokinetics of Twice Daily Midostaurin PKC412 Combined With Standard Chemotherapy and as a Single Agent Post-consolidation Therapy in Children With Untreated FLT3-mutated AML
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
True
If Expanded Access, NCT#:
NCT05219266
Has Expanded Access, NCT# Status:
NO_LONGER_AVAILABLE
Acronym:
None
Brief Summary:
This study will evaluate the safety efficacy and pharmacokinetics of midostaurin in combination with standard chemotherapy in pediatrics patients with newly diagnosed FLT3-mutated Acute Myeloid Leukemia The study has two parts Part 1 to define the Recommended Phase 2 Dose and Part 2 to evaluate safety and tolerability and efficacy of midostaurin Both parts will consist of 2 induction blocks 3 consolidation blocks 12 cycles of post-consolidation consisting of continuous therapy with midostaurin and a follow-up phase
Detailed Description:
This trial is an open label multi center single arm study to evaluate twice daily oral midostaurin with standard induction consolidation chemotherapy with sequential midostaurin therapy for 5 treatment blocks 2 induction blocks 3 consolidation blocks followed by single agent midostaurin post consolidation therapy for 12 cycles
The total maximum planned duration on treatment is 17 cycles 5 blocks and 12 cycles A block is defined as the time from start of study treatment to the time of hematopoietic recovery at the latest at Day D 42 or determination of persistent disease whichever occur first
In both Part 1 and Part 2 patients will receive the first course of induction chemotherapy according to local standard and duration is from 8 to 12 days Upon FLT3 mutation confirmation patients will receive midostaurin for 14 days After determination of remission and hematopoietic recovery patients will receive Block 2
In Part 1
Block 2 FLADx treatment duration is D1 to D6 and midostaurin from D8 to D21 Patients who achieve documented CR and hematopoietic recovery at the latest at D42 from the first day of Block 2 will receive Block 3
Block 3 consolidation HAM treatment duration is D1 to D4 followed by midostaurin D8 to D21 Patients who achieve hematopoietic recovery at the latest at D42 from the first day of Block 3 will receive Block 4 Patients who relapse will discontinue further study treatment
Block 4 HA3E treatment duration is D1 to D5 followed by midostaurin D8 to D21 Patients who achieve hematopoietic recovery at the latest at D42 from the first day of Block 4 will receive Block 5
Block 5 HiDAC treatment duration is D1 to D3 followed by midostaurin D8 to D21 Patients who relapse will discontinue further study treatment
Patients in continuous remission with hematopoietic recovery will receive continuous post consolidation therapy of midostaurin during 12 cycles 28 days per cycle
In Part 1 of the study patients in cohorts of 3 will receive sequential midostaurin administered at 30mgm2bid If the 30mgm2 bid is well tolerated as measured by the Dose Limited Toxicity DLT rate during Bock 1 additional patients in cohort of 3 will be treated with sequential midostaurin at 60mgm2 bid When the recommended phase 2 dose RP2D is confirmed subsequent patients will be treated in Part 2 of the study at the RP2D
In Part 2
Block 2 HAM treatment duration is D1 to D4 and midostaurin from D8 to D21 Patients who achieve documented CR and hematopoietic recovery at the latest at D42 from the first day of Block 2 will receive Block 3
Block 3 consolidation HA3E treatment duration is D1 to D5 followed by midostaurin D8 to D21 Patients who achieve hematopoietic recovery at the latest at D42 from the first day of Block 3 will receive Block 4 Patients who relapse will discontinue further study treatment
Block 4 HAM treatment duration is D1 to D4 followed by midostaurin D8 to D21 Patients who achieve hematopoietic recovery at the latest at D42 from the first day of Block 4 will receive Block 5
Block 5 HiDAC treatment duration is D1 to D3 followed by midostaurin D8 to D21 Patients who relapse will discontinue further study treatment
Patients in continuous remission with hematopoietic recovery will receive continuous post consolidation therapy of midostaurin during 12 cycles 28 days per cycle Patients who relapse will discontinue further study treatment
The total maximum planned duration on treatment is 17 cycles 5 blocks and 12 cycles A block is defined as the time from start of study treatment to the time of hematopoietic recovery at the latest at Day D 42 or determination of persistent disease whichever occur first
In both Part 1 and Part 2 patients will receive the first course of induction chemotherapy according to local standard and duration is from 8 to 12 days Upon FLT3 mutation confirmation patients will receive midostaurin for 14 days After determination of remission and hematopoietic recovery patients will receive Block 2
In Part 1
Block 2 FLADx treatment duration is D1 to D6 and midostaurin from D8 to D21 Patients who achieve documented CR and hematopoietic recovery at the latest at D42 from the first day of Block 2 will receive Block 3
Block 3 consolidation HAM treatment duration is D1 to D4 followed by midostaurin D8 to D21 Patients who achieve hematopoietic recovery at the latest at D42 from the first day of Block 3 will receive Block 4 Patients who relapse will discontinue further study treatment
Block 4 HA3E treatment duration is D1 to D5 followed by midostaurin D8 to D21 Patients who achieve hematopoietic recovery at the latest at D42 from the first day of Block 4 will receive Block 5
Block 5 HiDAC treatment duration is D1 to D3 followed by midostaurin D8 to D21 Patients who relapse will discontinue further study treatment
Patients in continuous remission with hematopoietic recovery will receive continuous post consolidation therapy of midostaurin during 12 cycles 28 days per cycle
In Part 1 of the study patients in cohorts of 3 will receive sequential midostaurin administered at 30mgm2bid If the 30mgm2 bid is well tolerated as measured by the Dose Limited Toxicity DLT rate during Bock 1 additional patients in cohort of 3 will be treated with sequential midostaurin at 60mgm2 bid When the recommended phase 2 dose RP2D is confirmed subsequent patients will be treated in Part 2 of the study at the RP2D
In Part 2
Block 2 HAM treatment duration is D1 to D4 and midostaurin from D8 to D21 Patients who achieve documented CR and hematopoietic recovery at the latest at D42 from the first day of Block 2 will receive Block 3
Block 3 consolidation HA3E treatment duration is D1 to D5 followed by midostaurin D8 to D21 Patients who achieve hematopoietic recovery at the latest at D42 from the first day of Block 3 will receive Block 4 Patients who relapse will discontinue further study treatment
Block 4 HAM treatment duration is D1 to D4 followed by midostaurin D8 to D21 Patients who achieve hematopoietic recovery at the latest at D42 from the first day of Block 4 will receive Block 5
Block 5 HiDAC treatment duration is D1 to D3 followed by midostaurin D8 to D21 Patients who relapse will discontinue further study treatment
Patients in continuous remission with hematopoietic recovery will receive continuous post consolidation therapy of midostaurin during 12 cycles 28 days per cycle Patients who relapse will discontinue further study treatment
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 |
|---|---|---|---|
| 2017-004830-28 | EUDRACT_NUMBER | None | None |