Minnelide for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

Inclusion Criteria

• Patients must have relapsed or refractory acute myeloid leukemia (AML) (excluding acute promyelocytic leukemia) * Relapsed patients must have received at least 1 induction chemotherapy regimen or 2 cycles of a hypomethylating agent and achieved a complete response (CR), followed by relapse of disease * Refractory patients must have received at least 1 induction chemotherapy regimen or 2 cycles of hypomethylating agent without achieving a CR
• Adult patients age 18 years or older
• Ineligible to receive any other standard of care therapy with a defined benefit including bone marrow transplantation
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Total bilirubin =< 1.5 times the institutional upper limit of normal
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 x institutional upper limit of normal
• Creatinine =< 2 mg/dL OR creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• White blood cell (WBC) count < 20,000/uL before administration of minnelide on cycle 1 day 1. Hydroxyurea may be utilized during cycle 1 as a method of cytoreduction to keep WBC < 20,000/uL to prevent complications from uncontrolled leukocytosis and to allow sufficient time for minnelide to be effective. * Note: Hydroxyurea may also be used to suppress the WBC to < 20,000/uL to qualify patients for the study
• Adequate cardiac function as determined by 2-dimensional (2D) echocardiogram with ejection fraction >= 50%
• Be able and willing to adhere to the study visit schedule and other protocol requirements
• Must be able to swallow capsules and have no evidence of gastrointestinal (GI) tract abnormality that would alter the absorption of oral medications
• The effects of minnelide on the developing human fetus are unknown. For this reason, women of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to beginning study treatment
• Patients of childbearing potential must practice contraception. Females of childbearing potential: Recommendation is for 2 effective contraceptive methods during the study. Adequate forms of contraception are abstinence, double barrier methods (condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral, Depo-Provera, or injectable contraceptives, intrauterine devices, and tubal ligation. Male patients with female partners who are of childbearing potential: Recommendation is for male and partner to use at least 2 effective contraceptive methods, as described above, during the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with minnelide, breastfeeding mothers must agree to discontinue nursing if the mother is treated with minnelide
• Provision of signed and dated informed consent document
• Patients with prior allogeneic stem cell transplant who experience relapse of AML are eligible if they are off of immunosuppressive therapy and without any evidence of graft-versus-host disease (GVHD)

Exclusion Criteria

• Patients may not have received any therapy with any investigational products, systemic anti-neoplastic therapy, or radiotherapy within 14 days prior to cycle 1 day 1. Use of hydroxyurea is allowed prior to enrollment and up to the end of cycle 1 upon treatment initiation
• Major surgery within 28 days prior to cycle 1 day 1
• New York Heart Association class III or IV heart failure, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on an electrocardiogram (EKG)
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
• Known, active human immunodeficiency virus (HIV), hepatitis A, B or C infection (prior hepatitis C infection that has been treated and determined to be cured is allowed)
• Symptomatic central nervous system involvement with leukemia
• Women with positive serum or urine pregnancy test within 24 hours prior to beginning study treatment
• A concurrent second active and non-stable malignancy with the exception of non-melanoma skin cancer or carcinoma in-situ