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

This study is currently recruiting participants.
Verified September 2013 by Stanford University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Bruno C. Medeiros, Stanford University
ClinicalTrials.gov Identifier:
NCT01846624
First received: April 30, 2013
Last updated: September 14, 2013
Last verified: September 2013
  Purpose

This phase II trial studies how well giving decitabine together with midostaurin works in treating older patients with newly diagnosed acute myeloid leukemia. Decitabine and midostaurin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
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 Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Secondary Acute Myeloid Leukemia
Untreated Adult Acute Myeloid Leukemia
Drug: decitabine
Drug: midostaurin
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Decitabine in Combination With Midostaurin (PKC412) for Elderly Patients With Newly Diagnosed FLT3-ITD/TKD Positive Acute Myeloid Leukemia

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Complete remission (CR) rate [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: June 2013
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (decitabine, midostaurin)

INDUCTION THERAPY: Patients receive decitabine IV over 1 hour on days 1-10 and midostaurin PO BID on days 11-28. 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: Patients receive decitabine IV over 1 hour on days 1-5 and midostaurin PO BID on days 6-28. Treatment repeats every 28 days for up to 12 courses (including induction therapy) in the absence of disease progression or unacceptable toxicity.

Drug: decitabine
Given IV
Other Names:
  • 5-aza-dCyd
  • 5AZA
  • DAC
Drug: midostaurin
Given PO
Other Names:
  • N-benzoyl-staurosporine
  • PKC412
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the efficacy of midostaurin when administered in combination with a fixed dose of decitabine, administered sequentially, in elderly patients (age >= 60 years) with fms-related tyrosine kinase 3 (FLT3)- internal tandem duplication (ITD)/tyrosine kinase domain (TKD)-positive acute myeloid leukemia (AML) (as measured by complete remission rate).

II. To assess the safety profile of this combination in elderly patients with FLT3-ITD/TKD-positive AML for both induction and post-remission therapy (adverse events [AEs]/serious adverse events [SAEs] as determined by Common Terminology Criteria for Adverse Events [CTCAE] version 4.0).

SECONDARY OBJECTIVES:

I. To determine overall survival for all patients and duration of response during the time period of study monitoring.

OUTLINE:

INDUCTION THERAPY: Patients receive decitabine intravenously (IV) over 1 hour on days 1-10 and midostaurin orally (PO) twice daily (BID) on days 11-28. 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: Patients receive decitabine IV over 1 hour on days 1-5 and midostaurin PO BID on days 6-28. 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.

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Newly diagnosed AML (according to 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) (i.e., decitabine or azacitidine)
  • Confirmed FLT3-ITD or FLT3-TKD mutation, measured on bone marrow aspirate as part of screening prior to study enrollment; sample will be submitted to Stanford clinical lab and sent out for commercially available test at Laboratory for Personalized Molecular Medicine
  • 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 x 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 of greater than two months

Exclusion Criteria:

  • Patients receiving concomitant treatment with other anti-neoplastic agents, with the exception of hydroxyurea; however, prior treatment with DNMTi therapy (i.e., decitabine or azacitidine) for MDS is allowed
  • Anti-neoplastic treatment less than 4 weeks prior to enrollment, with the exception of hydroxyurea
  • Inability to swallow or absorb drug
  • Active opportunistic infection or treatment for opportunistic infection within four weeks of first day of study drug dosing
  • 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
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to midostaurin and/or decitabine
  • Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of midostaurin
  • Any other known disease (except carcinoma in-situ), concurrent severe and/or uncontrolled medical condition (e.g. 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
  • A known confirmed diagnosis of human immunodeficiency virus (HIV) infection or active viral hepatitis because of uncertain toxicity profile of midostaurin in this patient population
  • Patients who have received any investigational agent within 4 weeks of enrollment
  • Patients who have had any surgical procedure, excluding central venous catheter placement or other minor procedures (e.g. skin biopsy) within 14 days of day 1
  • Unwillingness or inability to comply with the protocol
  • Known active central nervous system (CNS) malignancy
  • Previous or current history of a myeloproliferative disease
  • 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 III or IV
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test
  • 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 include:

    • Total abstinence (when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
    • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been 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%), for example hormone vaginal ring or transdermal hormone contraception
    • 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

      • In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01846624

Locations
United States, California
Stanford University Cancer Institute Recruiting
Stanford, California, United States, 94305
Contact: Jack Taw    650-723-2781    jtaw@stanford.edu   
Principal Investigator: Bruno C. de Medeiros         
Sponsors and Collaborators
Bruno C. Medeiros
Investigators
Principal Investigator: Bruno C. Medeiros Stanford University Hospitals and Clinics
  More Information

No publications provided

Responsible Party: Bruno C. Medeiros, Assistant Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT01846624     History of Changes
Other Study ID Numbers: HEMAML0022, NCI-2013-00868, 25737
Study First Received: April 30, 2013
Last Updated: September 14, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Additional relevant MeSH terms:
Congenital Abnormalities
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Decitabine
Staurosporine
4'-N-benzoylstaurosporine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 22, 2014