Acute Myeloid LeukemiaPhase 1NCT01130662
Combination of Decitabine and Midostaurin in Patients Older Than 60 With Newly Diagnosed or Relapsed Refractory Acute Myeloid Leukemia
A Phase 1 study testing combination therapy using decitabine and midostaurin in people with Acute Myeloid Leukemia, run by University of Kansas at 1 site in United States.
Trial summary
The purpose of this study is to determine the tolerated dose of the combination of decitabine and midostaurin as induction (first cycle of chemotherapy) and consolidation (additional chemotherapy once a patient goes into remission) in people greater than 60 years with newly diagnosed AML or adult patients with… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- combination therapy using decitabine and midostaurin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2010to Oct 2011
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥ 60 years of age with newly diagnosed AML that is not eligible for standard induction or ≥ 18 years of age with relapsed/refractory AML
- Histologically documented AML (except t(15;17)according to the World Health Association (WHO) criteria
- Karnofsky performance status ≥ 70
- Must have the following lab values:
- AST and ALT < or equal to 2.5 x Upper Limit of Normal (ULN)
- Serum Bilirubin < or equal to 2.5 x ULN
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- Serum Creatinine < or equal to 2.5 x ULN
- Must give written informed consent
- Left ventricular ejection fraction ≥ 50%
Who cannot join
- Prior allogeneic, syngeneic, or autologous bone marrow transplant or stem cell transplant less than 2 months previously
- Uncontrolled active infection
- Known impairment of GI function or GI disease that may significantly alter the absorption of midostaurin
- Female patients who are pregnant or breast-feeding or adults of reproductive potential not using an effective method of birth control. Barrier contraceptives must be used throughout the study in both sexes. Women of childbearing potential must have a negative serum pregnancy test 48 hours prior to administration of midostaurin. Women considered not of childbearing potential include any of the following: no menses for at least 5 years or menses within 5 years but amenorrheic for at least 2 months and luteinizing hormone (LH) and follicular stimulating hormone (FSH) values within normal range (according to definition of postmenopausal for laboratory used) or bilateral oophorectomy or radiation castration and amenorrheic for at least 3 months.
- Other known disease (except carcinoma in-situ) concurrent severe and/or uncontrolled medical condition (eg uncontrolled diabetes, cardiovascular disease including congestive heart failure, myocardial infarction within 6 months and poorly controlled hypertension, chronic renal disease, or active uncontrolled infection) which could compromise participation in the study.
- Impaired cardiac function including any of the following:
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- Screening ECG with a QTc > 450 msec
- Congenital long QT syndrome
- History or presence of sustained ventricular tachycardia
- Any history of ventricular fibrillation or torsades de pointes
- Bradycardia defined as HR less than 50 bpm
- Right bundle branch block + left anterior hemiblock (bifascicular block)
- Myocardial infarction or unstable angina < 6 months prior to starting study drug
- CHF NY Heart Association class III or IV
- Ejection fraction < 50% assessed by MUGA or ECHO scan within 14 days of Day 1
- Known confirmed diagnosis of HIV infection or active viral hepatitis
- Received any investigational agent within 30 days prior to Day 1
- Any surgical procedure, excluding central venous catheter placement, bone marrow biopsy or other minor procedures (eg skin biopsy) within 14 days of Day 1
- Unwilling or unable to comply with the protocol
- Known malignant disease of the central nervous system
- Any pulmonary infiltrate including those suspected to be of infectious origin. In particular, patients with resolution of clinical symptoms of pulmonary infection but with residual pulmonary infiltrates on chest x-ray are not eligible until pulmonary infiltrates have completely resolved
- Patients with prior midostaurin (PKC412) treatment are excluded
- Patients receiving any other investigational agents or have received other investigational agents within 30 days of enrollment
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to midostaurin and/or decitabine
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Kansas Medical Center, Westwood Campus
Kansas City, Kansas, 66205
About this study
Official title: Phase I Open-Label Study of Decitabine in Combination With Midostaurin (PKC412) for Elderly (Age ≥ 60) Newly Diagnosed or Relapsed/Refractory Adult Patients With Acute Myeloid Leukemia
The purpose of this study is to determine the tolerated dose of the combination of decitabine and midostaurin as induction (first cycle of chemotherapy) and consolidation (additional chemotherapy once a patient goes into remission) in people greater than 60 years with newly diagnosed AML or adult patients with relapsed/refractory disease.
Read the detailed description
The development of a primarily outpatient treatment option for AML that is also capable of providing significant disease control is a priority for most clinicians. To address the need for less toxic, more effective treatments for older patients with AML, the purpose of this Phase 1 single institution study is to evaluate the safety and efficacy of midostaurin and decitabine administered in combination.
Decitabine is an epigenetic modifier of gene expression that has been shown to be well-tolerated in this population at the dose schedule proposed in this study, with reasonable efficacy. Although its precise mechanism of action is incompletely understood, it is postulated to work by reactivating the expression of key tumor suppressor genes silenced in tumor cells by reversing a pattern of hypermethylation of promotor elements.
Midostaurin is an oral agent that has been shown to inhibit FLT3 kinase in preclinical in vitro and in vivo studies, as well as clinically in patients with both ITD and TKD FLT3 mutations (FLT3mut). Both directly and indirectly, midostaurin also potently inhibits multiple other molecular targets thought to be important for the pathogenesis of AML. These targets include VEGFR-1, a VEGF receptor; c-kit; H- and K-ras; as well as the multidrug resistant gene, MDR.
The addition of midostaurin to a decitabine regimen of previously established efficacy and tolerability will allow us to evaluate the hypothesis that two drugs that are believed to work through distinct mechanisms of action may act together to improve the responses of patients treated with decitabine alone, without significant additional toxicity.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- combination therapy using decitabine and midostaurin
- Keywords
- acute myeloid leukemia, AML, Relapsed AML, Refractory AML
- 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.
combination therapy using decitabine and midostaurinDrug
Also called Dacogen, PKC412
Cohort 1:
Decitabine 20mg/m2 IV daily on days 1-5 to be repeated every 28 days. Midostaurin 25mg bid days 8-21 of each cycle.
Cohort 2:
Decitabine 20mg/m2 IV daily on days 1-5 to be repeated every 28 days. Midostaurin 50mg bid days 8-21 of each cycle.
Cohort 3:
Decitabine 20mg/m2 IV daily on days 1-5 to be repeated every 28 days. Midostaurin 50mg bid x 28 days of each cycle.
| Study group | Role | What they receive |
|---|---|---|
| Decitabine Midostaurin combination | Experimental | Not described Receives: Drug: combination therapy using decitabine and midostaurin |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine a tolerated dose of the combination of decitabine and midostaurin as induction and consolidation in patients ≥ 60 years with newly diagnosed AML not eligible for standard induction or adult patients with relapsed/refractory disease.
Measured: 3 months per patient
Secondary outcomes (1)
Explore potential association between clinical response and FLT-3 status in patients treated in each cohort; assess toxicity of combination in each dosing cohort
Measured: 3 months per patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2010 (estimated)
- Study startMar 2010
- Primary completionOct 2011
- Study completionOct 2011
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.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Kansas
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Casey Williams, PharmD, Principal investigator, University of Kansas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01130662
- Sponsor's protocol ID
- 12010
- Other IDs
- CPCK412AUS06T
- Status last verified
- Mar 2013
- First submitted
- 24 May 2010
- Last updated
- 26 Mar 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Open-Label Study of Decitabine in Combination With Midostaurin (PKC412) for Elderly (Age ≥ 60) Newly Diagnosed or Relapsed/Refractory Adult Patients With Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT01130662
- Acronym / sponsor ID
- 12010
- Conditions
- Acute Myeloid Leukemia
- Keywords
- acute myeloid leukemia, AML, Relapsed AML, Refractory AML
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of KansasUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Mar 2010
- Primary completion
- Oct 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 26 May 2010 (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.
The purpose of this study is to determine the tolerated dose of the combination of decitabine and midostaurin as induction (first cycle of chemotherapy) and consolidation (additional chemotherapy once a patient goes into remission) in people greater than 60 years with newly diagnosed AML or adult patients with relapsed/refractory disease.
Detailed description
The development of a primarily outpatient treatment option for AML that is also capable of providing significant disease control is a priority for most clinicians. To address the need for less toxic, more effective treatments for older patients with AML, the purpose of this Phase 1 single institution study is to evaluate the safety and efficacy of midostaurin and decitabine administered in combination.
Decitabine is an epigenetic modifier of gene expression that has been shown to be well-tolerated in this population at the dose schedule proposed in this study, with reasonable efficacy. Although its precise mechanism of action is incompletely understood, it is postulated to work by reactivating the expression of key tumor suppressor genes silenced in tumor cells by reversing a pattern of hypermethylation of promotor elements.
Midostaurin is an oral agent that has been shown to inhibit FLT3 kinase in preclinical in vitro and in vivo studies, as well as clinically in patients with both ITD and TKD FLT3 mutations (FLT3mut). Both directly and indirectly, midostaurin also potently inhibits multiple other molecular targets thought to be important for the pathogenesis of AML. These targets include VEGFR-1, a VEGF receptor; c-kit; H- and K-ras; as well as the multidrug resistant gene, MDR.
The addition of midostaurin to a decitabine regimen of previously established efficacy and tolerability will allow us to evaluate the hypothesis that two drugs that are believed to work through distinct mechanisms of action may act together to improve the responses of patients treated with decitabine alone, without significant additional toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Decitabine Midostaurin combination | Experimental | Drug: combination therapy using decitabine and midostaurin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- ≥ 60 years of age with newly diagnosed AML that is not eligible for standard induction or ≥ 18 years of age with relapsed/refractory AML
- Histologically documented AML (except t(15;17)according to the World Health Association (WHO) criteria
- Karnofsky performance status ≥ 70
- Must have the following lab values:
- AST and ALT < or equal to 2.5 x Upper Limit of Normal (ULN)
Key exclusion criteria (24 listed)
- Prior allogeneic, syngeneic, or autologous bone marrow transplant or stem cell transplant less than 2 months previously
- Uncontrolled active infection
- Known impairment of GI function or GI disease that may significantly alter the absorption of midostaurin
- Female patients who are pregnant or breast-feeding or adults of reproductive potential not using an effective method of birth control. Barrier contraceptives must be used throughout the study in both sexes. Women of childbearing potential must have a negative serum pregnancy test 48 hours prior to administration of midostaurin. Women considered not of childbearing potential include any of the following: no menses for at least 5 years or menses within 5 years but amenorrheic for at least 2 months and luteinizing hormone (LH) and follicular stimulating hormone (FSH) values within normal range (according to definition of postmenopausal for laboratory used) or bilateral oophorectomy or radiation castration and amenorrheic for at least 3 months.
- Other known disease (except carcinoma in-situ) concurrent severe and/or uncontrolled medical condition (eg uncontrolled diabetes, cardiovascular disease including congestive heart failure, myocardial infarction within 6 months and poorly controlled hypertension, chronic renal disease, or active uncontrolled infection) which could compromise participation in the study.
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 |
|---|---|---|
| combination therapy using decitabine and midostaurinAlso: Dacogen, PKC412Cohort 1: Decitabine 20mg/m2 IV daily on days 1-5 to be repeated every 28 days. Midostaurin 25mg bid days 8-21 of each cycle. Cohort 2: Decitabine 20mg/m2 IV daily on days 1-5 to be repeated every 28 days. Midostaurin 50mg bid days 8-21 of each cycle. Cohort 3: Decitabine 20mg/m2 IV daily on days 1-5 to be repeated every 28 days. Midostaurin 50mg bid x 28 days of each cycle. | Drug | Decitabine Midostaurin combination |
Primary outcome
To determine a tolerated dose of the combination of decitabine and midostaurin as induction and consolidation in patients ≥ 60 years with newly diagnosed AML not eligible for standard induction or adult patients with relapsed/refractory disease.
Time frame: 3 months per patient
1 secondary outcome
Explore potential association between clinical response and FLT-3 status in patients treated in each cohort; assess toxicity of combination in each dosing cohort
Time frame: 3 months per patient
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2013.
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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.
Casey Williams, PharmD principal investigator
University of Kansas Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing combination therapy using decitabine and midostaurin in people with Acute Myeloid Leukemia, run by University of Kansas at 1 site in United States.
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 9 inclusion and 24 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: finished, as of the sponsor's last update on 26 Mar 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To determine a tolerated dose of the combination of decitabine and midostaurin as induction and consolidation in patients ≥ 60 years with newly diagnosed AML not eligible for standard induction or adult patients with relapsed/refractory disease. (time frame: 3 months per patient). 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 26 Mar 2013.