- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01846624
Decitabine and Midostaurin in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia
A Phase 2 Study of Decitabine in Combination With Midostaurin (PKC412) for Elderly Patients With Newly Diagnosed FLT3-ITD/TKD Positive Acute Myeloid Leukemia
Study Overview
Status
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)
- Secondary AML (Adult)
- Untreated AML (Adult)
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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California
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Stanford, California, United States, 94305
- Stanford University School of Medicine
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
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
- 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
Exclusion Criteria:
- 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
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Decitabine, then midostaurin
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. |
Given IV
Other Names:
Given PO
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Complete Remission (CR) Rate
Time Frame: Up to 1 year
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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.
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Up to 1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response Rate (ORR)
Time Frame: up to 1 year
|
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).
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up to 1 year
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Median Duration of Response (DoR)
Time Frame: Up to 1 year
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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.
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Up to 1 year
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Progression-free Survival (PFS)
Time Frame: Up to 2 years
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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. |
Up to 2 years
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Overall Survival (OS)
Time Frame: Up to 2 years
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Survival is reported as the number and proportion of participants that received midostaurin who remained alive 2 years after starting midostaurin treatment.
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Up to 2 years
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: David J Iberri, MD, Stanford University
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Bone Marrow Diseases
- Hematologic Diseases
- Myelodysplastic Syndromes
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Decitabine
- Azacitidine
- Midostaurin
- Staurosporine
Other Study ID Numbers
- IRB-25737
- HEMAML0022 (Registry Identifier: OnCore)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Acute Myeloid Leukemia (AML) With Multilineage Dysplasia Following Myelodysplastic Syndrome, in Adults
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Centre Hospitalier Universitaire de NiceUnknownMyelodysplastic Syndromes or Acute Myeloid Leukemia With Multilineage DysplasiaFrance, Monaco
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University of Wisconsin, MadisonNational Cancer Institute (NCI)CompletedRecurrent Adult Acute Myeloid Leukemia | Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome | Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities | Adult Acute Myeloid Leukemia With Del(5q) | Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) | Adult... and other conditionsUnited States
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Fred Hutchinson Cancer CenterNational Cancer Institute (NCI); National Heart, Lung, and Blood Institute...CompletedRecurrent Adult Acute Myeloid Leukemia | Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome | Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities | Adult Acute Myeloid Leukemia With Del(5q) | Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) | Adult... and other conditionsUnited States, Germany
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Alison WalkerNovartis; Millennium Pharmaceuticals, Inc.CompletedAcute Myeloid Leukemia | Recurrent Adult Acute Myeloid Leukemia | Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities | Adult Acute Myeloid Leukemia With Del(5q) | Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) | Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) | Adult Acute Myeloid... and other conditionsUnited States
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Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)TerminatedAcute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome | Adult Acute Minimally Differentiated Myeloid Leukemia (M0) | Adult Acute Myeloblastic Leukemia Without Maturation (M1) | Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities | Adult Acute Myeloid... and other conditionsUnited States
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National Cancer Institute (NCI)CompletedAcute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome | Adult Acute Minimally Differentiated Myeloid Leukemia (M0) | Adult Acute Monoblastic Leukemia (M5a) | Adult Acute Monocytic Leukemia (M5b) | Adult Acute Myeloblastic Leukemia With Maturation (M2) | Adult... and other conditionsUnited States
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Roswell Park Cancer InstituteNational Cancer Institute (NCI); Teva Pharmaceutical Industries, Ltd.TerminatedAcute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome | Adult Acute Megakaryoblastic Leukemia (M7) | Adult Acute Minimally Differentiated Myeloid Leukemia (M0) | Adult Acute Monoblastic Leukemia (M5a) | Adult Acute Monocytic Leukemia (M5b) | Adult Acute Myeloblastic... and other conditionsUnited States
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National Cancer Institute (NCI)CompletedRecurrent Adult Acute Myeloid Leukemia | Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome | Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities | Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) | Adult Acute Myeloid Leukemia With t(16;16)(p13... and other conditionsUnited States
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ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)Active, not recruitingAcute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome | Adult Acute Megakaryoblastic Leukemia (M7) | Adult Acute Minimally Differentiated Myeloid Leukemia (M0) | Adult Acute Monoblastic Leukemia (M5a) | Adult Acute Monocytic Leukemia (M5b) | Adult Acute Myeloblastic... and other conditionsUnited States, Israel, India
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National Cancer Institute (NCI)CompletedAcute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome | Adult Acute Megakaryoblastic Leukemia (M7) | Adult Acute Minimally Differentiated Myeloid Leukemia (M0) | Adult Acute Monoblastic Leukemia (M5a) | Adult Acute Monocytic Leukemia (M5b) | Adult Acute Myeloblastic... and other conditionsUnited States
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Eisai Inc.TerminatedMyelodysplastic SyndromesUnited States
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M.D. Anderson Cancer CenterNational Cancer Institute (NCI); Astex Pharmaceuticals, Inc.RecruitingChronic Phase Chronic Myelogenous Leukemia | Philadelphia Chromosome Positive | BCR-ABL1 Positive Chronic Myelogenous Leukemia | BCR-ABL1 PositiveUnited States