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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Recruitment Status : Withdrawn (Logistical and administrative issues)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

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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia With Gene Mutations Adult Acute Myeloid Leukemia in Remission Drug: Midostaurin Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Primary Completion Date : April 2018
Actual Study Completion Date : April 2018


Arm Intervention/treatment
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.
Drug: Midostaurin
Given PO
Other Names:
  • Rydapt
  • CGP 41251
  • N-benzoyl-staurosporine
  • PKC-412




Primary Outcome Measures :
  1. Event-free survival [ Time Frame: Up to 1 year ]
  2. 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 ]
  3. 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.

  4. 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.


Secondary Outcome Measures :
  1. Relapse rate after allogeneic transplant [ Time Frame: Up to 1 year ]
    Described using proportions.



Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02723435


Sponsors and Collaborators
Stanford University
Investigators
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Principal Investigator: David Iberri, MD Stanford University

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Responsible Party: David Iberri, Clinical Assistant Professor, Stanford University
ClinicalTrials.gov Identifier: NCT02723435     History of Changes
Other Study ID Numbers: IRB-31582
NCI-2016-00424 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
HEMAML0022-EXT ( Other Identifier: OnCore )
First Posted: March 30, 2016    Key Record Dates
Last Update Posted: May 4, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Midostaurin
Staurosporine
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action