Ignite Creation Date:
2025-12-24 @ 11:44 PM
Ignite Modification Date:
2026-01-03 @ 6:36 PM
Study NCT ID:
NCT02680951
Status:
WITHDRAWN
Last Update Posted:
2018-04-19
First Post:
2016-02-09
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Dasatinib in Combination With Chemotherapy for Relapsed or Refractory Core Binding Factor Acute Myeloid Leukemia
Sponsor:
Emory University
Organization:
Study Overview
Official Title:
Dasatinib in Combination With Chemotherapy for Relapsed or Refractory Core Binding Factor Acute Myeloid Leukemia: A Phase I Study (AflacLL1401)
Status:
WITHDRAWN
Status Verified Date:
2018-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Withdrawn due to lack of participants.
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will examine the appropriate dose and side effects of dasatinib, when it is given with the standard of care chemotherapy for children and adolescents with Acute Myeloid Leukemia (AML).
Detailed Description:
This Phase I study is for children and adolescents who have acute myelogenous leukemia (AML) that has come back (relapsed) or has become resistant (refractory) to standard therapies. Researchers want to know if a drug called dasatinib is safe when used together with standard chemotherapy in treating patients who have relapsed or have resistant AML. Their leukemia has a particular genetic mutation, called core-binding factor.
This type of leukemia has an increase of a cancer promoting protein called c-KIT. Dasatinib can target this protein in laboratory experiments. Laboratory and other studies suggest that dasatinib may prevent acute myeloid leukemia cells from growing and may lead to the destruction of leukemia cells.
The main goal of this study is to find a safe dose of dasatinib and to find out the side effects of dasatinib when it is given in combination with standard chemotherapy to children and adolescents. Similar studies are currently being done in adult patients. Dasatinib has been proven safe and effective in the treatment of other types of leukemia, both by itself and in combination with standard chemotherapy. It is not, however, FDA-approved for use in children.
Three to six participants will receive the starting dose of the drug. If the side effects are not too severe, the next group of participants will take the study drug at a higher dose level. Up to two dose levels of the study drug will be tested. Dasatinib is given by mouth once daily on days 6 to 29 of each 42-day cycle. Participants may receive two cycles in this study.
In addition to dasatinib, participants receive chemotherapy intravenously (IV) with fludarabine, cytarabine, idarubicin, as well as in the spinal fluid (intrathecal or IT chemotherapy). Intrathecal chemotherapy includes cytarabine at the start of each cycle. These drugs are part of standard AML treatment. If at the time of study entry a subject has leukemia cells in their spinal fluid (CNS leukemia), they may receive additional intrathecal chemotherapy with cytarabine, methotrexate, and hydrocortisone (IT triples) during each cycle.
Required research tests include pharmacokinetic (PK) and pharmacodynamics (PD) blood draws (about 1 teaspoon each time) during cycle 1. Optional research tests include extra marrow (about 1 teaspoon each time) for genetic testing and banking of marrow (1 teaspoon) for future studies about cancer.
Primary Objectives of this study are:
* To evaluate the safety of combining dasatinib with reinduction chemotherapy comprised of idarubicin, fludarabine and cytarabine (Ida - FLU/Ara) in children with relapsed or refractory core binding factor acute myeloid leukemia (CBF AML)
* To characterize the toxicity profile of this combination in pediatric patients with relapsed or refractory CBF AML
Secondary Objectives of this study are:
* To estimate the response rates to the combination chemotherapy in the context of a Phase I study, in children with AML in first or greater relapse or refractory to induction chemotherapy
* To determine the genotype of c-KIT exons 8 and 17 and correlate with response rate
* To characterize c-KIT expression of bone marrow blasts at study entry and at the end of course 1 of therapy and describe any correlation with response to therapy
Exploratory Objectives are:
* To investigate descriptively the pharmacodynamic modulation of c-KIT target, Stat3, in a cell line by patient-derived plasma
* To perform RNA sequencing on bone marrow samples at study entry in order to describe the prevalence of mutations in AML associated genes, including c-KIT, and correlate descriptively with progression free survival
* To collect biology specimens at study entry and completion of therapy for future biology studies
This type of leukemia has an increase of a cancer promoting protein called c-KIT. Dasatinib can target this protein in laboratory experiments. Laboratory and other studies suggest that dasatinib may prevent acute myeloid leukemia cells from growing and may lead to the destruction of leukemia cells.
The main goal of this study is to find a safe dose of dasatinib and to find out the side effects of dasatinib when it is given in combination with standard chemotherapy to children and adolescents. Similar studies are currently being done in adult patients. Dasatinib has been proven safe and effective in the treatment of other types of leukemia, both by itself and in combination with standard chemotherapy. It is not, however, FDA-approved for use in children.
Three to six participants will receive the starting dose of the drug. If the side effects are not too severe, the next group of participants will take the study drug at a higher dose level. Up to two dose levels of the study drug will be tested. Dasatinib is given by mouth once daily on days 6 to 29 of each 42-day cycle. Participants may receive two cycles in this study.
In addition to dasatinib, participants receive chemotherapy intravenously (IV) with fludarabine, cytarabine, idarubicin, as well as in the spinal fluid (intrathecal or IT chemotherapy). Intrathecal chemotherapy includes cytarabine at the start of each cycle. These drugs are part of standard AML treatment. If at the time of study entry a subject has leukemia cells in their spinal fluid (CNS leukemia), they may receive additional intrathecal chemotherapy with cytarabine, methotrexate, and hydrocortisone (IT triples) during each cycle.
Required research tests include pharmacokinetic (PK) and pharmacodynamics (PD) blood draws (about 1 teaspoon each time) during cycle 1. Optional research tests include extra marrow (about 1 teaspoon each time) for genetic testing and banking of marrow (1 teaspoon) for future studies about cancer.
Primary Objectives of this study are:
* To evaluate the safety of combining dasatinib with reinduction chemotherapy comprised of idarubicin, fludarabine and cytarabine (Ida - FLU/Ara) in children with relapsed or refractory core binding factor acute myeloid leukemia (CBF AML)
* To characterize the toxicity profile of this combination in pediatric patients with relapsed or refractory CBF AML
Secondary Objectives of this study are:
* To estimate the response rates to the combination chemotherapy in the context of a Phase I study, in children with AML in first or greater relapse or refractory to induction chemotherapy
* To determine the genotype of c-KIT exons 8 and 17 and correlate with response rate
* To characterize c-KIT expression of bone marrow blasts at study entry and at the end of course 1 of therapy and describe any correlation with response to therapy
Exploratory Objectives are:
* To investigate descriptively the pharmacodynamic modulation of c-KIT target, Stat3, in a cell line by patient-derived plasma
* To perform RNA sequencing on bone marrow samples at study entry in order to describe the prevalence of mutations in AML associated genes, including c-KIT, and correlate descriptively with progression free survival
* To collect biology specimens at study entry and completion of therapy for future biology studies
Study Oversight
Has Oversight DMC:
True
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?: