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Midostaurin in Treating Older Patients With Mutated Acute Myeloid Leukemia Post-Transplant

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ClinicalTrials.gov Identifier: NCT02723435
Recruitment Status : Withdrawn (Logistical and administrative issues)
First Posted : March 30, 2016
Last Update Posted : May 4, 2018
Sponsor:
Information provided by (Responsible Party):
David Iberri, Stanford University

Tracking Information
First Submitted Date  ICMJE March 25, 2016
First Posted Date  ICMJE March 30, 2016
Last Update Posted Date May 4, 2018
Study Start Date  ICMJE Not Provided
Actual Primary Completion Date April 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 25, 2016)
  • Event-free survival [ Time Frame: Up to 1 year ]
  • Incidence of adverse events using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 30 days ]
  • Overall survival [ Time Frame: Up to 1 year ]
    Calculated and reported with Kaplan Meier curves. The statistical analyses will focus on estimation rather than hypothesis testing. Two-sided 95% confidence intervals will be presented, using the Clopper-Pearson method for proportions and using Greenwood's formula for time to event outcomes.
  • Relapse free survival [ Time Frame: Up to 1 year ]
    Calculated and reported with Kaplan Meier curves. The statistical analyses will focus on estimation rather than hypothesis testing. Two-sided 95% confidence intervals will be presented, using the Clopper-Pearson method for proportions and using Greenwood's formula for time to event outcomes.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02723435 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 25, 2016)
Relapse rate after allogeneic transplant [ Time Frame: Up to 1 year ]
Described using proportions.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Midostaurin in Treating Older Patients With Mutated Acute Myeloid Leukemia Post-Transplant
Official Title  ICMJE An Open-Label Extension Study of Post-Transplant Maintenance Midostaurin (PKC412) in Elderly Patients (Age ≥ 60 Years) With FLT3-ITD/TKD Mutated AML Who Previously Received Midostaurin and Decitabine as Part of Study HEMAML0022 / CPKC412AUS27T
Brief Summary This phase 2 trial studies the side effects and how well midostaurin works in treating older patients with acute myeloid leukemia with change in genetic material post-hematopoietic cell transplantation. Midostaruin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving midostaruin post-transplant may improve patient outcomes.
Detailed Description

PRIMARY OBJECTIVES:

I. To determine the efficacy and safety of maintenance midostaurin (a fms related tyrosine kinase 3 [FLT3] inhibitor) for elderly patients with FLT3-internal tandem duplication (ITD)/tyrosine kinase domain (TKD) mutated acute myeloid leukemia (AML) who were previously enrolled on study HEMAML0022/CPKC412AUS27T and have then undergone allogeneic transplant.

SECONDARY OBJECTIVES:

I. To determine whether maintenance midostaurin after allogeneic transplant decreases the relapse rate in patients with FLT3-ITD/TKD mutated AML.

OUTLINE:

Beginning 30 days post-hematopoietic cell transplantation (HCT), patients receive midostaurin orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then up to 1 year.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myeloid Leukemia With Gene Mutations
  • Adult Acute Myeloid Leukemia in Remission
Intervention  ICMJE Drug: Midostaurin
Given PO
Other Names:
  • Rydapt
  • CGP 41251
  • N-benzoyl-staurosporine
  • PKC-412
Study Arms  ICMJE Experimental: Midostaurin
Beginning 30 days post-HCT, participants receive oral midostaurin twice-a-day in 28-day treatment cycles, continuing up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Drug: Midostaurin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: May 1, 2018)
0
Original Estimated Enrollment  ICMJE
 (submitted: March 25, 2016)
20
Actual Study Completion Date  ICMJE April 2018
Actual Primary Completion Date April 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

INCLUSION CRITERIA

  • Elderly patients with FLT3-mutated acute myeloid leukemia (AML)
  • Prior enrollment in Stanford study IRB-25737
  • In continued complete remission
  • ≥ 30 days but ≤ 90 days post allogeneic hematopoietic cell transplant (HCT); treatment on this study protocol must begin before day 90 post-HCT
  • Absolute neutrophil count (ANC) ≥ 1000 cells/uL
  • Hemoglobin ≥ 8.0 g/dL and not requiring regular transfusions
  • Platelets ≥ 50,000 cells/uL and not requiring regular transfusions
  • Aspartate aminotransferase (AST) ≤ 2.5 times upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) ≤ 2.5 X ULN
  • Serum bilirubin ≤ 2.5 times ULN
  • Ability to give written informed consent, including via legally authorized representative
  • Corrected QT (QTc) ≤ 450 msec
  • Ejection fraction (EF) ≥ 45% by 2-dimensional transthoracic echocardiography (TTE) or multiple-gated acquisition (MUGA)
  • Sexually active males, including vasectomized males, must agree via informed consent to use a condom during vaginal, anal, or oral intercourse, while taking midostaurin and for 5 months after stopping midostaurin
  • Females must have or be:

    • Negative pregnancy test, within 21 days of the first dose of midostaurin OR
    • Not of childbearing potential as follows:

      • Has undergone a hysterectomy or bilateral oophorectomy;
      • Has not had menses at any time in the preceding 24 consecutive months

EXCLUSION CRITERIA

  • Uncontrolled acute graft-vs-host disease (GVHD) grade 3 to 4
  • Uncontrolled active infection
  • Evidence of active AML (eg, circulating peripheral blasts on complete blood count)
  • Known confirmed diagnosis of human immunodeficiency virus (HIV) infection
  • Known confirmed diagnosis of active viral hepatitis
  • QTc > 450 msec
  • Congenital long QT syndrome
  • History of presence of sustained ventricular tachycardia, history of ventricular fibrillation or torsades de pointes
  • Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm)
  • Bifascicular block (right bundle branch block plus left anterior hemiblock)
  • Congestive heart failure (CHF) New York Heart Association (NYHA) class 3 or 4
  • Cardiac ejection fraction (EF) < 45% within 28 days prior to starting cycle 1
  • Other known malignancy (except carcinoma in situ)
  • Other concurrent severe and/or uncontrolled medical condition which could compromise participation in the study, eg:

    • Uncontrolled diabetes
    • Chronic active pancreatitis
    • Myocardial infarction within 6 months
    • Poorly-controlled hypertension
    • Chronic kidney disease
  • Received any investigational agent within 30 days prior to day 1
  • Antineoplastic chemotherapy or radiotherapy within 28 days prior to cycle 1
  • No plans for concurrent chemotherapy while on study (exception: antineoplastic drugs used as part of GVHD prophylaxis or treatment)
  • Any surgical procedure, excluding central venous catheter placement, bone marrow biopsy or other minor procedures (eg, skin biopsy) within 14 days of day 1
  • Unwillingness or inability to comply with the protocol
  • Known malignant disease of the central nervous system
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to midostaurin
  • Concomitant use of strong inhibitors of cytochrome P450 family 3 subfamily A member 4 (CYP3A4)
  • Pregnant or lactating
  • Women of child-bearing potential
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT02723435
Other Study ID Numbers  ICMJE IRB-31582
NCI-2016-00424 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
HEMAML0022-EXT ( Other Identifier: OnCore )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party David Iberri, Stanford University
Study Sponsor  ICMJE Stanford University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: David Iberri, MD Stanford University
PRS Account Stanford University
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP