Topics

Dasatinib in Combination With Chemotherapy for Relapsed or Refractory Core Binding Factor Acute Myeloid Leukemia

2016-02-15 21:02:39 | BioPortfolio

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).

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

Acute Myeloid Leukemia

Intervention

Dasatinib, Fludarabine, Cytarabine, Idarubicin, Intrathecal (IT) cytarabine

Location

Children's Healthcare of Atlanta
Atlanta
Georgia
United States
30322

Status

Recruiting

Source

Emory University

Results (where available)

View Results

Links

Published on BioPortfolio: 2016-02-15T21:02:39-0500

Clinical Trials [2299 Associated Clinical Trials listed on BioPortfolio]

Dasatinib, Cytarabine, and Idarubicin in Treating Patients With High-Risk Acute Myeloid Leukemia

This phase I/II trial studies the side effects and best dose of dasatinib when given together with cytarabine and idarubicin hydrochloride and to see how well they work in treating patient...

Clofarabine, Idarubicin, and Cytarabine (CIA) Versus Fludarabine, Idarubicin, and Cytarabine (FLAI) in Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplastic Syndrome

The goal of this clinical research study is to learn if the combination of clofarabine, idarubicin, and cytarabine, or the combination of fludarabine, idarubicin, and cytarabine can help c...

Fludarabine, Cytarabine, Filgrastim and Idarubicin in Core Binding Factor (CBF) Leukemias

The goal of this clinical research study is to learn if idarubicin can be added to the combination of fludarabine, cytarabine, and Neupogen (Filgrastim) without increasing the risk of side...

Pravastatin, Idarubicin, and Cytarabine in Treating Patients With Acute Myeloid Leukemia

RATIONALE: Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from di...

Idarubicin and Cytarabine With or Without Bevacizumab in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

RATIONALE: Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Bevacizumab may stop the gr...

PubMed Articles [6482 Associated PubMed Articles listed on BioPortfolio]

Idarubicin, cytarabine, and nivolumab in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a single-arm, phase 2 study.

Outcomes for younger patients with acute myeloid leukaemia have moderately improved over the past two decades owing to better supportive care and recent introduction of novel targeted agents. Blocking...

Safety and efficacy of oral panobinostat plus chemotherapy in patients aged 65 years or younger with high-risk acute myeloid leukemia.

The role of histone deacetylase inhibitors in the treatment of acute myeloid leukemia (AML) is not well characterized. The current study evaluated the safety and efficacy of panobinostat in combinatio...

BST-236, a novel cytarabine prodrug for patients with acute leukemia unfit for standard induction: a phase 1/2a study.

High-dose cytarabine is the backbone of acute myeloid leukemia (AML) treatment. Nevertheless, its use in older patients is considerably limited due to increased toxicity. BST-236 (INN aspacytarabine) ...

FMS-like tyrosine kinase 3 (FLT3) modulates key enzymes of nucleotide metabolism implicated in cytarabine responsiveness in pediatric acute leukemia.

Treatment of pediatric acute leukemia might involve combined therapies targeting the FMS-like tyrosine kinase 3 (FLT3) receptor (i.e. quizartinib - AC220) and nucleotide metabolism (cytarabine - AraC)...

Modified cladribine, cytarabine, and G-CSF as a salvage regimen in patients with relapsed/refractory acute myeloid leukemia: a bridge to myeloablative allogeneic hematopoietic stem cell transplantation.

Patients with primary refractory or early relapsed acute myeloid leukemia (AML) have a dismal prognosis, and the treatment options for these patients are limited. The present study retrospectively exa...

Medical and Biotech [MESH] Definitions

Congener of CYTARABINE that is metabolized to cytarabine and thereby maintains a more constant antineoplastic action.

A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472)

A pyrimidine nucleoside formed in the body by the deamination of CYTARABINE.

A triphosphate nucleotide analog which is the biologically active form of CYTARABINE. It inhibits nuclear DNA synthesis.

A pediatric acute myeloid leukemia involving both myeloid and monocytoid precursors. At least 20% of non-erythroid cells are of monocytic origin.

More From BioPortfolio on "Dasatinib in Combination With Chemotherapy for Relapsed or Refractory Core Binding Factor Acute Myeloid Leukemia"

Quick Search

Relevant Topics

Pediatrics
Pediatrics is the general medicine of childhood. Because of the developmental processes (psychological and physical) of childhood, the involvement of parents, and the social management of conditions at home and at school, pediatrics is a specialty. With ...

Leukemia
Leukemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases. In turn, it is part of the even broader grou...

Clincial Trials
In a clinical trial or interventional study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or change...


Searches Linking to this Trial