Acute Myeloid LeukemiaPhase 1NCT02680951
Dasatinib in Combination With Chemotherapy for Relapsed or Refractory Core Binding Factor Acute Myeloid Leukemia
A Phase 1 study testing Dasatinib, Fludarabine and Cytarabine in people with Acute Myeloid Leukemia, run by Emory University.
Trial 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). Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Dasatinib, Fludarabine and Cytarabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Dec 2015to 15 Dec 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Histologically confirmed relapsed or refractory Acute Myeloid Leukemia (AML) and meet the following criteria: Relapsed disease is defined as AML in 1st or greater marrow relapse; Refractory disease is defined as AML which failed to go into remission after 1st or greater relapse, OR AML which failed to go into remission after two or more induction attempts from original diagnosis
- ≥ 5% blasts by morphology in the bone marrow or molecular evidence of at least 0.1% leukemic blasts in the bone marrow
- Definitive evidence of t(8;21) or inv(16) by a CLIA approved cytogenetics laboratory from initial diagnosis
- CNS or other sites of extramedullary disease. No cranial irradiation is allowed during the protocol therapy
- Lansky ≥ 50 for patients ≤ 16 years old; Karnofsky ≥ 50 for patients > 16 years old
- Have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiation therapy prior to entering this study
Show all 13Show fewer
- Have adequate renal and hepatic functions
- A shortening fraction greater than or equal to 27% by echocardiogram, OR ejection fraction greater than or equal to 50% by radionuclide angiogram (MUGA)
- Must not have any evidence of dyspnea at rest, exercise intolerance, and must have a pulse oximetry > 94% at sea level
- Patients with a seizure disorder may be enrolled if well controlled on anticonvulsants at a dose that has been stable for at least 14 days
- Female participants of childbearing potential must have a negative urine or serum pregnancy test confirmed within 24 hours prior to enrollment
- Female participants with infants must agree not to breastfeed their infants while on this study
- Male and female participants of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study and for a minimum of 6 months after study treatment
Who cannot join
- Known allergy to any of the drugs used in the study
- Systemic fungal, bacterial, viral or other infection of which they exhibit ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment
- Any clinically significant cardiovascular disease including: myocardial infarction or ventricular tachyarrhythmia within 6 months, prolonged QTc > 480 msec by the Fridericia correction, major conduction abnormality, such as 2nd or 3rd degree heart block or symptomatic bundle branch block, unless a cardiac pacemaker is present
- Plans to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period
- Refractory to red blood cell or platelet transfusions
- Receiving anti-coagulation therapy
Show all 10Show fewer
- A need to administer drugs that inhibit platelet function, such as aspirin or clopidogrel
- Receiving any of the following potent CYP3A4 inducers or inhibitors: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's Wort
- Significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results
- Individuals with Down syndrome and DNA fragility syndromes (such as Fanconi anemia, Bloom syndrome)
About this study
Official title: Dasatinib in Combination With Chemotherapy for Relapsed or Refractory Core Binding Factor Acute Myeloid Leukemia: A Phase I Study (AflacLL1401)
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).
Read the 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
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Dasatinib, Fludarabine, Cytarabine, Idarubicin, Intrathecal (IT) cytarabine
- Keywords
- Pediatric, Adolescent
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DasatinibDrug
Also called Sprycel, BMS-354825
Administered orally on a once daily schedule based on the dose level assigned to the patient at enrollment (60, 80, or 100mg/m2/day). Patients may adjust the time they take dasatinib as long as they take the drug approximately every 24 hours
FludarabineDrug
Also called Fludara
30 mg/m2/dose, intravenous infusion over 30 minutes, once daily, on days 1 to 5, total 5 doses
Participants with body weight less than 12Kg, the fludarabine dose will be corrected as follows: [weight (Kg) x dose (per m2)] divided by 30
CytarabineDrug
Also called Depocyt, Cytosar-U
2000 mg/m2/dose intravenous infusion over 1 to 3 hours, starting 4 hours after the beginning of fludarabine, once daily, on days 1 to 5, total 5 doses
Participants with body weight less than 12Kg, the cytarabine dose will be corrected as follows: [weight (Kg) x dose (per m2)] divided by 30
IdarubicinDrug
Also called Idamycin
8mg/m2/dose intravenous infusion over 15 minutes, once daily, on days 3 to 5, total 3 doses
Participants with body weight less than 12Kg, the idarubicin dose will be corrected as follows: [weight (Kg) x dose (per m2)] divided by 30
Intrathecal (IT) cytarabineDrug
Also called Depocyt, Cytosar-U
Given intrathecally to all participants on day 1 of course 1 and 2. Omit on day 1 of course 1 if participant received IT therapy within 7 days prior to study enrollment. Intrathecal chemotherapy may be given during the end of course 1 disease evaluation (spinal fluid and bone marrow aspiration) and may be repeated every 7 days with bone marrow evaluations per institutional preference.
Cytarabine dose defined by age:
- 30 mg for patients age 1 - 1.99
- 50 mg for patients age 2 - 2.99
- 70 mg for patients ≥3 years of age
The participant may receive intrathecal triple therapy (ITT) if persistent blasts are present in the cerebral spinal fluid (CSF) based on the treating physician's clinical judgment.
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 1 | Experimental | Study participants #1 - #6 receive dose level 1 of dasatinib (60/mg/m2/day) in addition to the standard treatment, for up to 2 courses. Each treatment course is 29 days.
Treatment course 1 consists of:
* Fludarabine at a dose of 30mg/m2, intravenously once daily on days 1-5
* Cytarabine at a dose of 2000mg/m2, intravenously once daily on days 1-5
* Idarubicin at a dose of 8mg/m2, intravenously once daily on days 3-5
* Intrathecal cytarabine on day 1 according to standard age specific dosing guidelines
* Dasatinib orally, once daily on days 6-29
Participants achieving a response of standard disease or better are eligible for course 2 consisting of dasatinib with fludarabine and cytarabine alone. Receives: Drug: Dasatinib; Drug: Fludarabine; Drug: Cytarabine; Drug: Idarubicin; Drug: Intrathecal (IT) cytarabine |
| Dose Level 2 | Experimental | Study participants # 7 - # 12 receive dose level 2 of dasatinib (80/mg/m2/day) in addition to the standard treatment (up to 2 courses), if the participants receiving Dose Level 1 did not experience intolerable side effects. Each treatment course is 29 days.
Treatment course 1 consists of:
* Fludarabine at a dose of 30mg/m2, intravenously once daily on days 1-5
* Cytarabine at a dose of 2000mg/m2, intravenously once daily on days 1-5
* Idarubicin at a dose of 8mg/m2, intravenously once daily on days 3-5
* Intrathecal cytarabine on day 1 according to standard age specific dosing guidelines
* Dasatinib orally, once daily on days 6-29
Participants achieving a response of standard disease or better are eligible for course 2 consisting of dasatinib with fludarabine and cytarabine alone. Receives: Drug: Dasatinib; Drug: Fludarabine; Drug: Cytarabine; Drug: Idarubicin; Drug: Intrathecal (IT) cytarabine |
| Dose Level 3 | Experimental | Study participants # 13 - # 18 receive dose level 3 of dasatinib (100/mg/m2/day) in addition to the standard treatment (up to 2 courses), if the participants receiving Dose Level 2 did not experience intolerable side effects. Each treatment course is 29 days.
Treatment course 1 consists of:
* Fludarabine at a dose of 30mg/m2, intravenously once daily on days 1-5
* Cytarabine at a dose of 2000mg/m2, intravenously once daily on days 1-5
* Idarubicin at a dose of 8mg/m2, intravenously once daily on days 3-5
* Intrathecal cytarabine on day 1 according to standard age specific dosing guidelines
* Dasatinib orally, once daily on days 6-29
Participants achieving a response of standard disease or better are eligible for course 2 consisting of dasatinib with fludarabine and cytarabine alone. Receives: Drug: Dasatinib; Drug: Fludarabine; Drug: Cytarabine; Drug: Idarubicin; Drug: Intrathecal (IT) cytarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of Dasatinib assessed by the Number of Adverse Events
The number of adverse events throughout the duration of the study will be collected to assess the safety of dasatinib.
Measured: Duration of Study (Up to 161 Days)
Number of Dose-Limiting Toxicities (DLT)
The number of dose limiting toxicities (DLT) as defined by grade 3 or higher non-hematologic adverse events persisting for great than 48 hours without resolution to a grade 2 or less, grade 2 pleural effusion that persists longer than 1 week, failure to recover an absolute neutrophil count (ANC) of greater than 500/µL, and platelet count of greater than 50,000/µL. Dose level toxicities will be assessed in the first course only.
Measured: Duration of Course 1 (Up to 42 Days)
Maximum Tolerated Dose (MTD)
The MTD will be the highest dose at which 1 or fewer of six patients experience dose-limiting toxicities (DLT).
Measured: Duration of Study (Up to 161 Days)
Secondary outcomes (2)
Remission Status assessed by Bone Marrow Aspiration/Biopsy
A single bone marrow aspiration/biopsy will be performed to assess remission status between day 29 and 43. The exact time point of the bone marrow aspiration/biopsy is dependent on blood count recovery (absolute neutrophil count of greater than 500). Day 43 is the last day remission status must be assessed.
Measured: Between Day 29 and Day 43
Effect of Dasatinib on c-KIT Expression assessed by Phosphorylation of Stat3
The effect of dasatinib on c-KIT expression will be measured by phosphorylation of Stat3 in a core binding factor acute myeloid leukemia (CBF AML) cell line treated with patient plasma.
Measured: Baseline, End of course 1 (Up to 49 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2016 (estimated)
- Study startDec 2015
- Primary completion15 Dec 2017
- Study completion15 Dec 2017
Why it stopped: Withdrawn due to lack of participants.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Melinda Pauly, Emory University
- Investigators
- Melinda Pauly, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02680951
- Sponsor's protocol ID
- IRB00078620
- Status last verified
- Apr 2018
- First submitted
- 9 Feb 2016
- Last updated
- 19 Apr 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dasatinib in Combination With Chemotherapy for Relapsed or Refractory Core Binding Factor Acute Myeloid Leukemia: A Phase I Study (AflacLL1401)
- ClinicalTrials.gov ID
- NCT02680951
- Acronym / sponsor ID
- IRB00078620
- Conditions
- Acute Myeloid Leukemia
- Keywords
- Pediatric, Adolescent
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Withdrawn due to lack of participants.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- Dec 2015 (actual)
- Primary completion
- 15 Dec 2017 (actual)
- Study completion
- 15 Dec 2017 (actual)
- First posted
- 12 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose Level 1 | Experimental | Drug: Dasatinib, Drug: Fludarabine, Drug: Cytarabine, Drug: Idarubicin, Drug: Intrathecal (IT) cytarabineStudy participants #1 - #6 receive dose level 1 of dasatinib (60/mg/m2/day) in addition to the standard treatment, for up to 2 courses. Each treatment course is 29 days. Treatment course 1 consists of: * Fludarabine at a dose of 30mg/m2, intravenously once daily on days 1-5 * Cytarabine at a dose of 2000mg/m2, intravenously once daily on days 1-5 * Idarubicin at a dose of 8mg/m2, intravenously once daily on days 3-5 * Intrathecal cytarabine on day 1 according to standard age specific dosing guidelines * Dasatinib orally, once daily on days 6-29 Participants achieving a response of standard disease or better are eligible for course 2 consisting of dasatinib with fludarabine and cytarabine alone. |
| Dose Level 2 | Experimental | Drug: Dasatinib, Drug: Fludarabine, Drug: Cytarabine, Drug: Idarubicin, Drug: Intrathecal (IT) cytarabineStudy participants # 7 - # 12 receive dose level 2 of dasatinib (80/mg/m2/day) in addition to the standard treatment (up to 2 courses), if the participants receiving Dose Level 1 did not experience intolerable side effects. Each treatment course is 29 days. Treatment course 1 consists of: * Fludarabine at a dose of 30mg/m2, intravenously once daily on days 1-5 * Cytarabine at a dose of 2000mg/m2, intravenously once daily on days 1-5 * Idarubicin at a dose of 8mg/m2, intravenously once daily on days 3-5 * Intrathecal cytarabine on day 1 according to standard age specific dosing guidelines * Dasatinib orally, once daily on days 6-29 Participants achieving a response of standard disease or better are eligible for course 2 consisting of dasatinib with fludarabine and cytarabine alone. |
| Dose Level 3 | Experimental | Drug: Dasatinib, Drug: Fludarabine, Drug: Cytarabine, Drug: Idarubicin, Drug: Intrathecal (IT) cytarabineStudy participants # 13 - # 18 receive dose level 3 of dasatinib (100/mg/m2/day) in addition to the standard treatment (up to 2 courses), if the participants receiving Dose Level 2 did not experience intolerable side effects. Each treatment course is 29 days. Treatment course 1 consists of: * Fludarabine at a dose of 30mg/m2, intravenously once daily on days 1-5 * Cytarabine at a dose of 2000mg/m2, intravenously once daily on days 1-5 * Idarubicin at a dose of 8mg/m2, intravenously once daily on days 3-5 * Intrathecal cytarabine on day 1 according to standard age specific dosing guidelines * Dasatinib orally, once daily on days 6-29 Participants achieving a response of standard disease or better are eligible for course 2 consisting of dasatinib with fludarabine and cytarabine alone. |
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (13 listed)
- Histologically confirmed relapsed or refractory Acute Myeloid Leukemia (AML) and meet the following criteria: Relapsed disease is defined as AML in 1st or greater marrow relapse; Refractory disease is defined as AML which failed to go into remission after 1st or greater relapse, OR AML which failed to go into remission after two or more induction attempts from original diagnosis
- ≥ 5% blasts by morphology in the bone marrow or molecular evidence of at least 0.1% leukemic blasts in the bone marrow
- Definitive evidence of t(8;21) or inv(16) by a CLIA approved cytogenetics laboratory from initial diagnosis
- CNS or other sites of extramedullary disease. No cranial irradiation is allowed during the protocol therapy
- Lansky ≥ 50 for patients ≤ 16 years old; Karnofsky ≥ 50 for patients > 16 years old
Key exclusion criteria (10 listed)
- Known allergy to any of the drugs used in the study
- Systemic fungal, bacterial, viral or other infection of which they exhibit ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment
- Any clinically significant cardiovascular disease including: myocardial infarction or ventricular tachyarrhythmia within 6 months, prolonged QTc > 480 msec by the Fridericia correction, major conduction abnormality, such as 2nd or 3rd degree heart block or symptomatic bundle branch block, unless a cardiac pacemaker is present
- Plans to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period
- Refractory to red blood cell or platelet transfusions
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DasatinibAlso: Sprycel, BMS-354825Administered orally on a once daily schedule based on the dose level assigned to the patient at enrollment (60, 80, or 100mg/m2/day). Patients may adjust the time they take dasatinib as long as they take the drug approximately every 24 hours | Drug | Dose Level 1, Dose Level 2, Dose Level 3 |
| FludarabineAlso: Fludara30 mg/m2/dose, intravenous infusion over 30 minutes, once daily, on days 1 to 5, total 5 doses Participants with body weight less than 12Kg, the fludarabine dose will be corrected as follows: [weight (Kg) x dose (per m2)] divided by 30 | Drug | Dose Level 1, Dose Level 2, Dose Level 3 |
| CytarabineAlso: Depocyt, Cytosar-U2000 mg/m2/dose intravenous infusion over 1 to 3 hours, starting 4 hours after the beginning of fludarabine, once daily, on days 1 to 5, total 5 doses Participants with body weight less than 12Kg, the cytarabine dose will be corrected as follows: [weight (Kg) x dose (per m2)] divided by 30 | Drug | Dose Level 1, Dose Level 2, Dose Level 3 |
| IdarubicinAlso: Idamycin8mg/m2/dose intravenous infusion over 15 minutes, once daily, on days 3 to 5, total 3 doses Participants with body weight less than 12Kg, the idarubicin dose will be corrected as follows: [weight (Kg) x dose (per m2)] divided by 30 | Drug | Dose Level 1, Dose Level 2, Dose Level 3 |
| Intrathecal (IT) cytarabineAlso: Depocyt, Cytosar-UGiven intrathecally to all participants on day 1 of course 1 and 2. Omit on day 1 of course 1 if participant received IT therapy within 7 days prior to study enrollment. Intrathecal chemotherapy may be given during the end of course 1 disease evaluation (spinal fluid and bone marrow aspiration) and may be repeated every 7 days with bone marrow evaluations per institutional preference. Cytarabine dose defined by age: * 30 mg for patients age 1 - 1.99 * 50 mg for patients age 2 - 2.99 * 70 mg for patients ≥3 years of age The participant may receive intrathecal triple therapy (ITT) if persistent blasts are present in the cerebral spinal fluid (CSF) based on the treating physician's clinical judgment. | Drug | Dose Level 1, Dose Level 2, Dose Level 3 |
Primary outcome
Safety of Dasatinib assessed by the Number of Adverse Events
Time frame: Duration of Study (Up to 161 Days)
The number of adverse events throughout the duration of the study will be collected to assess the safety of dasatinib.
Number of Dose-Limiting Toxicities (DLT)
Time frame: Duration of Course 1 (Up to 42 Days)
The number of dose limiting toxicities (DLT) as defined by grade 3 or higher non-hematologic adverse events persisting for great than 48 hours without resolution to a grade 2 or less, grade 2 pleural effusion that persists longer than 1 week, failure to recover an absolute neutrophil count (ANC) of greater than 500/µL, and platelet count of greater than 50,000/µL. Dose level toxicities will be assessed in the first course only.
Maximum Tolerated Dose (MTD)
Time frame: Duration of Study (Up to 161 Days)
The MTD will be the highest dose at which 1 or fewer of six patients experience dose-limiting toxicities (DLT).
2 secondary outcomes
Remission Status assessed by Bone Marrow Aspiration/Biopsy
Time frame: Between Day 29 and Day 43
Effect of Dasatinib on c-KIT Expression assessed by Phosphorylation of Stat3
Time frame: Baseline, End of course 1 (Up to 49 days)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2018.
Related trials for Acute Myeloid Leukemia
RecruitingObservational study
A Long-term Follow-up Study of Patients With ARD103 CAR-T Cell Therapies
Acute Myeloid Leukemia, in Relapse, Acute Myeloid Leukemia, in Relapsed or Refractory
RecruitingPhase 2
MYELOMATCH: A Screening Study to Assign People With Myeloid Cancer to a Treatment Study or Standard of Care Treatment Within myeloMATCH (MyeloMATCH Screening Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
RecruitingPhase 1
225Ac-DOTA-Anti-CD38 Daratumumab Monoclonal Antibody With Fludarabine, Melphalan and Total Marrow and Lymphoid Irradiation as Conditioning Treatment for Donor Stem Cell Transplant in Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia and Myelodysplastic Syndrome
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
RecruitingPhase 2
Testing the Addition of Venetoclax or Gemtuzumab Ozogamicin (GO) to Usual Treatment Regimen (Cytarabine and Daunorubicin, "7+3") for Core Binding Factor Acute Myeloid Leukemia (CBF-AML) to Improve Response (A MYELOMATCH Treatment Trial)
Core Binding Factor Acute Myeloid Leukemia
RecruitingPhase 1/2
Phase I/II Trial: Engineered Donor Graft (Orca Q) for Pediatric Hematopoietic Cell Transplant (HCT)
Acute Myeloid Leukemia, Acute Lymphoid Leukemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Melinda Pauly, MD principal investigator
Emory University
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dasatinib, Fludarabine and Cytarabine in people with Acute Myeloid Leukemia, run by Emory University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 19 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of Dasatinib assessed by the Number of Adverse Events (time frame: Duration of Study (Up to 161 Days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2018.