Acute Myeloid Leukemia (AML) With Multilineage Dysplasia Following Myelodysplastic Syndrome, in AdultsPhase 2NCT01846624
Decitabine and Midostaurin in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia
A Phase 2 study testing Decitabine and Midostaurin in people with Acute Myeloid Leukemia (AML) With Multilineage Dysplasia Following Myelodysplastic Syndrome, in Adults and AML (Adult) With 11q23 (MLL) Abnormalities, run by David Iberri at 1 site in United States.
Trial summary
This phase 2 study evaluates the sequential combination of decitabine then midostaurin for the treatment of newly-diagnosed acute myeloid leukemia (AML) in older patients. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Acute Myeloid Leukemia (AML) With Multilineage Dysplasia Following Myelodysplastic Syndrome, in Adults, AML (Adult) With 11q23 (MLL) Abnormalities, AML (Adult) With Del (5q)
- What is being tested?
- Decitabine and Midostaurin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2013to 31 Aug 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Newly-diagnosed acute myeloid leukemia (AML) per the World Health Organization [WHO] 2008 classification [except t (15; 17)], including:
- De novo AML
- Secondary AML
- Secondary AML arising from previously-diagnosed myelodysplastic syndromes (MDS) treated with deoxyribonucleic acid (DNA) methyltransferase inhibitor (DNMTi) (ie, decitabine or azacitidine)
- FLT3-ITD mutation confirmed in bone marrow aspirate
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
Show all 14Show fewer
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
- Serum bilirubin ≤ 2.5 ULN
- Serum creatinine ≤ 1.5 mg/dL and/or creatinine clearance ≥ 50 mL/min
- Ejection fraction ≥ 50% by echocardiogram
- Unwillingness or inability to receive conventional chemotherapy
- Ability to understand and the willingness to sign a written informed consent document
- Ability to adhere to the study visit schedule and other protocol requirements
- Life expectancy > 2 months
Who cannot join
- Receiving concomitant treatment with other anti-neoplastic agents (EXCEPTION: hydroxyurea). Prior treatment with DNMTi therapy (ie, decitabine or azacitidine) for MDS is allowed
- Received anti-neoplastic treatment within 4 weeks prior to enrollment (EXCEPTION: hydroxyurea)
- Received any surgical procedure, excluding central venous catheter placement or other minor procedures (eg, skin biopsy) within 14 days of study day 1
- Received any investigational agent within 4 weeks prior to enrollment
- Previous or current history of a myeloproliferative disease
- Known active central nervous system (CNS) malignancy
Show all 30Show fewer
- Any other known disease (except carcinoma in-situ), concurrent severe and/or uncontrolled medical condition which could compromise participation in the study (eg, uncontrolled diabetes; cardiovascular disease including congestive heart failure; myocardial infarction within 6 months with poorly controlled hypertension; chronic renal disease; active uncontrolled infection)
- Active opportunistic infection or treatment for opportunistic infection within 4 weeks of first day of study drug dosing
- Known confirmed diagnosis of human immunodeficiency virus (HIV) infection or active viral hepatitis
- Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of midostaurin
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to midostaurin and/or decitabine
- Impaired cardiac function including any of the following:
- Screening electrocardiogram (ECG) with a corrected QT interval (QTc) > 450 msec
- Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm)
- Right bundle branch block + left anterior hemiblock (bifascicular block)
- Patients with myocardial infarction or unstable angina < 3 months prior to starting study drug
- Congestive heart failure (CHF) New York (NY) Heart Association class 3 or 4
- Inability to swallow or absorb drug
- Other medical or psychiatric illness or organ dysfunction or laboratory abnormality which in the opinion of the investigator would compromise the patient's safety or interfere with data interpretation
- Unwillingness or inability to comply with the protocol
- Pregnant
- nursing (lactating)
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they are using highly effective methods of contraception during dosing and for 3 months after midostaurin medication; highly effective contraception methods as follows:
- Total abstinence, when this is in line with the preferred and usual lifestyle of the subject [periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception]
- Female sterilization (surgical bilateral oophorectomy with or without hysterectomy; or tubal ligation at least six weeks before taking study treatment). In case of oophorectomy alone, reproductive status must be confirmed by follow-up hormone level assessment
- Male sterilization, at least 6 months prior to screening (for female subjects on the study, the vasectomized male partner should be the sole partner for that subject)
- Combination of any two of the following (a+b or a+c, or b+c):
- Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), eg, hormone vaginal ring or transdermal hormone contraception. For oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment
- Placement of an intrauterine device (IUD) or intrauterine system (IUS)
- Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University School of Medicine
Stanford, California, 94305
About this study
Official title: A Phase 2 Study of Decitabine in Combination With Midostaurin (PKC412) for Elderly Patients With Newly Diagnosed FLT3-ITD/TKD Positive Acute Myeloid Leukemia
This phase 2 study evaluates the sequential combination of decitabine then midostaurin for the treatment of newly-diagnosed acute myeloid leukemia (AML) in older patients.
Read the detailed description
Treatment with decitabine, a cytidine analog, then midostaurin, a multi-target protein kinase inhibitor (PKI), may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
- Conditions
- Acute Myeloid Leukemia (AML) With Multilineage Dysplasia Following Myelodysplastic Syndrome, in Adults, AML (Adult) With 11q23 (MLL) Abnormalities, AML (Adult) With Del (5q), AML (Adult) With Inv (16) (p13; q22), AML (Adult) With t (16;16) (p13; q22), AML (Adult) With t (8; 21) (q22; q22)
- Being tested
- Decitabine, Midostaurin
- Medical subject headings
- Leukemia, Myeloid, Acute, Congenital Abnormalities
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DecitabineDrug
Also called 5-aza-dCyd, 5AZA, DAC, Dacogen
Given IV
MidostaurinDrug
Also called N-benzoyl-staurosporine, PKC412
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Decitabine, then midostaurin | Experimental | INDUCTION THERAPY Subjects receive decitabine intravenously (IV) over 1 hour on days 1 to 10 and midostaurin orally (PO) twice daily (BID) on days 11 to 28. Treatment repeats every 28 days until documented bone marrow response is achieved or for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients achieving documented bone marrow response by course 6 continue treatment with induction therapy; patients achieving response after course 6 proceed to post-remission therapy.
POST-REMISSION THERAPY Subjects receive decitabine IV over 1 hour on days 1 to 5 and midostaurin PO BID on days 6 to 28. Treatment repeats every 28 days for up to 12 courses (including induction therapy) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for up to 1 year. Receives: Drug: Decitabine; Drug: Midostaurin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Remission (CR) Rate
The complete remission (CR) rate, or complete response rate, is reported as the sum and proportion of participants that achieved CR or CR with incomplete blood count recovery (CRi), within 12 months of starting midostaurin treatment.
- Complete remission (CR): Bone marrow blasts < 5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) > 1000/μL; platelet count > 100,000/μL; independence of red cell transfusions.
- CR with incomplete recovery (CRi): All CR criteria except for ANC < 1000/μL or platelet count < 100,000/μL.
- Partial remission (PR): All hematologic criteria of CR; except decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%.
Measured: Up to 1 year
Secondary outcomes (4)
Overall Response Rate (ORR)
Overall response rate (ORR) was assessed as the number and proportion of participants who received midostaurin and achieved a partial response (PR), complete response (CR), or complete response with incomplete blood count recovery (CRi).
- Complete remission (CR): Bone marrow blasts < 5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) > 1000/μL; platelet count > 100,000/μL; independence of red cell transfusions.
- CR with incomplete recovery (CRi): All CR criteria except for ANC < 1000/μL or platelet count < 100,000/μL.
- Partial remission (PR): All hematologic criteria of CR; except decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%.
Measured: up to 1 year
Median Duration of Response (DoR)
Response was assessed by evaluations conducted every 3 cycles (12 weeks). Once documented as partial response (PR), complete response (CR), or complete response with incomplete blood count recover (CRi), response status was confirmed every 12 weeks. In responding participants, duration of response was assessed from the start of treatment through the last documented response before documented progressive disease or death. The outcome is reported as the median value for duration of response, with full range.
- CR: Bone marrow blasts < 5%; absence of blasts with Auer rods; absence of extramedullary disease; ANC > 1000/μL; platelet > 100,000/μL; independence of red cell transfusions.
- CRi: All CR criteria except ANC < 1000/μL or platelet count < 100,000/μL.
- PR: All hematologic criteria of CR; except decrease of bone marrow blast percentage to 5% to 25%; \& decrease of pretreatment bone marrow blast percentage by at least 50%.
Measured: Up to 1 year
Progression-free Survival (PFS)
Progression-free survival (PFS) is reported as the number and proportion of participants who did not receive hematopoietic cell transplantation, and who did not experience disease progression or death for any reason within 2 years after starting midostaurin treatment.
Progressive disease: Bone marrow blasts ≥ 5%; or reappearance of blasts in the blood; or development of extramedullary disease.
Measured: Up to 2 years
Overall Survival (OS)
Survival is reported as the number and proportion of participants that received midostaurin who remained alive 2 years after starting midostaurin treatment.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2013 (estimated)
- Study startJun 2013
- Primary completion22 Jul 2016
- Study completion31 Aug 2016
Why it stopped: Accrual factor
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid Leukemia (AML) With Multilineage Dysplasia Following Myelodysplastic Syndrome, in AdultsStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- David Iberri
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, David Iberri, Stanford University
- Investigators
- David J Iberri, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01846624
- Sponsor's protocol ID
- IRB-25737
- Other IDs
- HEMAML0022
- Status last verified
- Sep 2018
- First submitted
- 30 Apr 2013
- Last updated
- 27 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Lowenberg B, Bloomfield CD; European LeukemiaNet. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010 Jan 21;115(3):453-74. doi: 10.1182/blood-2009-07-235358. Epub 2009 Oct 30.
PubMed 19880497
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Decitabine in Combination With Midostaurin (PKC412) for Elderly Patients With Newly Diagnosed FLT3-ITD/TKD Positive Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT01846624
- Acronym / sponsor ID
- IRB-25737
- Conditions
- Acute Myeloid Leukemia (AML) With Multilineage Dysplasia Following Myelodysplastic Syndrome, in Adults, AML (Adult) With 11q23 (MLL) Abnormalities, AML (Adult) With Del (5q), AML (Adult) With Inv (16) (p13; q22), AML (Adult) With t (16;16) (p13; q22), AML (Adult) With t (8; 21) (q22; q22)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Accrual factor
- Enrolment
- 13 participants (actual)
- Lead sponsor
- David IberriUniversity, hospital or other
- Study start
- Jun 2013
- Primary completion
- 22 Jul 2016 (actual)
- Study completion
- 31 Aug 2016 (actual)
- First posted
- 3 May 2013 (estimated)
- Results
- Posted 7 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase 2 study evaluates the sequential combination of decitabine then midostaurin for the treatment of newly-diagnosed acute myeloid leukemia (AML) in older patients.
Detailed description
Treatment with decitabine, a cytidine analog, then midostaurin, a multi-target protein kinase inhibitor (PKI), may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Decitabine, then midostaurin | Experimental | Drug: Decitabine, Drug: MidostaurinINDUCTION THERAPY Subjects receive decitabine intravenously (IV) over 1 hour on days 1 to 10 and midostaurin orally (PO) twice daily (BID) on days 11 to 28. Treatment repeats every 28 days until documented bone marrow response is achieved or for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients achieving documented bone marrow response by course 6 continue treatment with induction therapy; patients achieving response after course 6 proceed to post-remission therapy. POST-REMISSION THERAPY Subjects receive decitabine IV over 1 hour on days 1 to 5 and midostaurin PO BID on days 6 to 28. Treatment repeats every 28 days for up to 12 courses (including induction therapy) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for up to 1 year. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Newly-diagnosed acute myeloid leukemia (AML) per the World Health Organization [WHO] 2008 classification [except t (15; 17)], including:
- FLT3-ITD mutation confirmed in bone marrow aspirate
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
- Serum bilirubin ≤ 2.5 ULN
Key exclusion criteria (30 listed)
- Receiving concomitant treatment with other anti-neoplastic agents (EXCEPTION: hydroxyurea). Prior treatment with DNMTi therapy (ie, decitabine or azacitidine) for MDS is allowed
- Received anti-neoplastic treatment within 4 weeks prior to enrollment (EXCEPTION: hydroxyurea)
- Received any surgical procedure, excluding central venous catheter placement or other minor procedures (eg, skin biopsy) within 14 days of study day 1
- Received any investigational agent within 4 weeks prior to enrollment
- Previous or current history of a myeloproliferative disease
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 |
|---|---|---|
| DecitabineAlso: 5-aza-dCyd, 5AZA, DAC, DacogenGiven IV | Drug | Decitabine, then midostaurin |
| MidostaurinAlso: N-benzoyl-staurosporine, PKC412Given PO | Drug | Decitabine, then midostaurin |
Primary outcome
Complete Remission (CR) Rate
Time frame: Up to 1 year
The complete remission (CR) rate, or complete response rate, is reported as the sum and proportion of participants that achieved CR or CR with incomplete blood count recovery (CRi), within 12 months of starting midostaurin treatment. * Complete remission (CR): Bone marrow blasts < 5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) > 1000/μL; platelet count > 100,000/μL; independence of red cell transfusions. * CR with incomplete recovery (CRi): All CR criteria except for ANC < 1000/μL or platelet count < 100,000/μL. * Partial remission (PR): All hematologic criteria of CR; except decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%.
4 secondary outcomes
Overall Response Rate (ORR)
Time frame: up to 1 year
Median Duration of Response (DoR)
Time frame: Up to 1 year
Progression-free Survival (PFS)
Time frame: Up to 2 years
Overall Survival (OS)
Time frame: Up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19880497Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Lowenberg B, Bloomfield CD; European LeukemiaNet. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010 Jan 21;115(3):453-74. doi: 10.1182/blood-2009-07-235358. Epub 2009 Oct 30.
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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.
David J Iberri, MD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Decitabine and Midostaurin in people with Acute Myeloid Leukemia (AML) With Multilineage Dysplasia Following Myelodysplastic Syndrome, in Adults and AML (Adult) With 11q23 (MLL) Abnormalities, run by David Iberri 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 14 inclusion and 30 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: stopped early, as of the sponsor's last update on 27 Sep 2018. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Complete Remission (CR) Rate (time frame: Up to 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01846624, which also lists 1 linked publication.
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 27 Sep 2018.