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

• Status: Withdrawn
• Trial end date: 2018-04-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Stanford University
• Collaborator: National Cancer Institute (NCI)
• Treatments: 4'-N-benzoylstaurosporine; Midostaurin; Staurosporine

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