Ignite Creation Date:
2024-05-06 @ 12:20 PM
Last Modification Date:
2024-10-26 @ 12:57 PM
Study NCT ID:
NCT03735875
Status:
TERMINATED
Last Update Posted:
2023-10-16
First Post:
2018-11-02
Brief Title:
Venetoclax and Quizartinib in Treating Patients With FLT3-mutated Recurrent or Refractory Acute Myeloid Leukemia
Sponsor:
MD Anderson Cancer Center
Organization:
MD Anderson Cancer Center
Study Overview
Official Title:
A Phase IbII Study of Venetoclax in Combination With Quizartinib in FLT3-Mutated Acute Myelogenous Leukemia AML
Status:
TERMINATED
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
This study was terminated early due to other competing trials therefore did not go on to the Phase II portion of the study
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase IbII trial studies the side effects and best dose of venetoclax in combination with quizartinib and how well they work in treating patients with acute myeloid leukemia that has come back or does not respond to treatment and who are FLT3-mutation positive Venetoclax and quizartinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth
Detailed Description:
PRIMARY OBJECTIVES
I To determine the maximum tolerated dose MTD and the recommended phase 2 dose RP2D of the combination of venetoclax with quizartinib in FLT3-internal tandem duplication ITD mutated patients with relapsedrefractory acute myeloid leukemia AML Phase Ib II To determine the composite complete remission CR CRc rate including CR CRp complete remission with incomplete platelet recovery CRi complete remission with incomplete count recovery within 3 months of treatment initiation in FLT3-ITD mutated patients with relapsedrefractory AML Phase II
SECONDARY OBJECTIVES
I To determine the composite CRc rate including CR CRp CRi within 3 months of treatment initiation in FLT3-ITD mutated patients with relapsed refractory AML Phase Ib II To determine the overall response rate ORR including CRc partial remission PR within 3 months of treatment initiation in FLT3-ITD mutated patients with relapsedrefractory AML Phase Ib III To determine the duration of response DOR progression free survival event-free survival EFS overall survival OS and number of patients bridged to hematopoietic stem cell transplant HSCT and median duration to HSCT from the initiation of the combination in FLT3-ITD mutated patients with relapsed refractory AML Phase Ib IV To characterize the pharmacokinetic PK profiles of combination therapy of venetoclax and quizartinib in FLT3-ITD mutated patients with relapsedrefractory AML Phase Ib V To determine the ORR within 3 months of treatment initiation in FLT3-ITD mutated patients with relapsed refractory AML Phase II VI To determine the DOR progression-free survival PFS EFS OS and number of patients bridged to HSCT and median duration to HSCT from the initiation of the combination in FLT3-ITD mutated patients with relapsedrefractory AML Phase II VII To determine the safety and tolerability of the combination in FLT3-ITD mutated patients with relapsedrefractory AML Phase II
EXPLORATORY OBJECTIVES
I To investigate possible relationships between baseline next generation gene sequencing and clinical response to the combination
II To investigate quantitative changes of FLT3-ITD allelic burden with time and the extent of pharmacodynamics biomarker such as phosphorylated p-FLT3 p-ribosomal protein S6 kinase beta-1 p70S6K pERK pSTAT inhibition and the induction of apoptosis in the bone marrow and peripheral blasts in patients treated with the combination
III To investigate possible relationships between baseline gene expression signatures Bcl-2 family messenger ribonucleic acid mRNA and protein levels of AML blasts andor stem cell sub-population BH3 profiling of Bcl-2 family member dependency and ex vivo functional screen and clinical response to the combination
IV To analyze immune modulation including alterations in total and percent of CD3 T-cells total and percent of various T-cell subsets CD4-effector CD4-regs CD8 cytotoxic T-cells and total and percent of T-cellT-cell subsets expressing specific checkpoint receptorsligands with the combination
V To store andor analyze surplus blood or tissue including bone marrow if available for potential future exploratory research into molecular and immune factors that may influence response to venetoclax andor quizartinib where response is defined broadly to include efficacy tolerability or safety
OUTLINE This is a phase Ib dose-escalation study of quizartinib followed by a phase II study
Patients receive quizartinib orally PO once daily QD on days 1-28 and venetoclax PO QD beginning on day 8 of cycle 1 Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity Patients may continue treatment beyond 24 cycles at the discretion of the treating physician
After completion of study treatment patients are followed up at 30 days and then every 3-6 months for up to 5 years
I To determine the maximum tolerated dose MTD and the recommended phase 2 dose RP2D of the combination of venetoclax with quizartinib in FLT3-internal tandem duplication ITD mutated patients with relapsedrefractory acute myeloid leukemia AML Phase Ib II To determine the composite complete remission CR CRc rate including CR CRp complete remission with incomplete platelet recovery CRi complete remission with incomplete count recovery within 3 months of treatment initiation in FLT3-ITD mutated patients with relapsedrefractory AML Phase II
SECONDARY OBJECTIVES
I To determine the composite CRc rate including CR CRp CRi within 3 months of treatment initiation in FLT3-ITD mutated patients with relapsed refractory AML Phase Ib II To determine the overall response rate ORR including CRc partial remission PR within 3 months of treatment initiation in FLT3-ITD mutated patients with relapsedrefractory AML Phase Ib III To determine the duration of response DOR progression free survival event-free survival EFS overall survival OS and number of patients bridged to hematopoietic stem cell transplant HSCT and median duration to HSCT from the initiation of the combination in FLT3-ITD mutated patients with relapsed refractory AML Phase Ib IV To characterize the pharmacokinetic PK profiles of combination therapy of venetoclax and quizartinib in FLT3-ITD mutated patients with relapsedrefractory AML Phase Ib V To determine the ORR within 3 months of treatment initiation in FLT3-ITD mutated patients with relapsed refractory AML Phase II VI To determine the DOR progression-free survival PFS EFS OS and number of patients bridged to HSCT and median duration to HSCT from the initiation of the combination in FLT3-ITD mutated patients with relapsedrefractory AML Phase II VII To determine the safety and tolerability of the combination in FLT3-ITD mutated patients with relapsedrefractory AML Phase II
EXPLORATORY OBJECTIVES
I To investigate possible relationships between baseline next generation gene sequencing and clinical response to the combination
II To investigate quantitative changes of FLT3-ITD allelic burden with time and the extent of pharmacodynamics biomarker such as phosphorylated p-FLT3 p-ribosomal protein S6 kinase beta-1 p70S6K pERK pSTAT inhibition and the induction of apoptosis in the bone marrow and peripheral blasts in patients treated with the combination
III To investigate possible relationships between baseline gene expression signatures Bcl-2 family messenger ribonucleic acid mRNA and protein levels of AML blasts andor stem cell sub-population BH3 profiling of Bcl-2 family member dependency and ex vivo functional screen and clinical response to the combination
IV To analyze immune modulation including alterations in total and percent of CD3 T-cells total and percent of various T-cell subsets CD4-effector CD4-regs CD8 cytotoxic T-cells and total and percent of T-cellT-cell subsets expressing specific checkpoint receptorsligands with the combination
V To store andor analyze surplus blood or tissue including bone marrow if available for potential future exploratory research into molecular and immune factors that may influence response to venetoclax andor quizartinib where response is defined broadly to include efficacy tolerability or safety
OUTLINE This is a phase Ib dose-escalation study of quizartinib followed by a phase II study
Patients receive quizartinib orally PO once daily QD on days 1-28 and venetoclax PO QD beginning on day 8 of cycle 1 Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity Patients may continue treatment beyond 24 cycles at the discretion of the treating physician
After completion of study treatment patients are followed up at 30 days and then every 3-6 months for up to 5 years
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 |
|---|---|---|---|
| 2018-0608 | OTHER | M D Anderson Cancer Center | None |
| NCI-2018-02396 | REGISTRY | None | None |