Decitabine and Midostaurin in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

NCT01846624 | Terminated Phase 2 Results DMC

• 2 other identifiers: IRB-25737HEMAML0022
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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.

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)

Outcome Measures

Primary Outcomes (1)

• 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%.

  Up to 1 year

Secondary Outcomes (4)

• Overall Response Rate (ORR)

  up to 1 year

• Median Duration of Response (DoR)

  Up to 1 year

• Progression-free Survival (PFS)

  Up to 2 years

• Overall Survival (OS)

  Up to 2 years

Study Arms (1)

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.

Drug: Decitabine; Drug: Midostaurin

Interventions

Decitabine DRUG

Given IV

Also known as: 5-aza-dCyd, 5AZA, DAC, Dacogen

Decitabine, then midostaurin

Midostaurin DRUG

Given PO

Also known as: N-benzoyl-staurosporine, PKC412

Decitabine, then midostaurin

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• David Iberri: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (1)

• 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.

  PMID: 19880497 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Congenital Abnormalities

Interventions

Decitabine; midostaurin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: David Joseph Iberri, MD; Clinical Assistant Professor (Hematology)
• Organization: Stanford University Medical Center

diberri@stanford.edu

650-498-6000

Study Officials

• David J Iberri, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: April 30, 2013
• First Posted: May 3, 2013
• Study Start: June 1, 2013
• Primary Completion: July 22, 2016
• Study Completion: August 31, 2016
• Last Updated: September 27, 2018
• Results First Posted: September 7, 2018

Record last verified: 2018-09

Locations

US (1)