Dose Escalation Study of Minnelide in Relapsed or Refractory Acute Myeloid Leukemia

Inclusion Criteria:

• Adults ages 18 years or older.

• Participant must have relapsed or refractory acute myeloid leukemia (AML) (excludingacute promyelocytic leukemia).

• Relapsed patients must have received at least 1 induction chemotherapy regimen ortwo 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 ortwo cycles of hypomethylating agent without achieving a CR.

• Eastern Cooperative Oncology Group (ECOG) performance status <2.

• Participants must have acceptable organ function.

• Be able and willing to adhere to the study visit schedule and other protocolrequirements.

• Must be able to swallow capsules and have no evidence of GI tract abnormality thatwould alter the absorption of oral medications.

• The effects of Minnelide on the developing human fetus are unknown. For this reason,women of child-bearing potential must have a negative serum or urine pregnancy testwithin 24 hours prior to beginning study treatment.

• Participants of childbearing potential must practice contraception. Females ofchildbearing potential: Recommendation is for 2 effective contraceptive methodsduring the study. Male participants with female partners who are of childbearingpotential: Recommendation is for male and partner to use at least 2 effectivecontraceptive methods, as described above, during the study. Should a woman becomepregnant or suspect she is pregnant while participating in this study, she shouldinform her treating physician immediately.

• Because there is an unknown but potential risk for adverse events in nursing infantssecondary to treatment of the mother with Minnelide, breastfeeding mothers mustagree 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 AMLare eligible if they are off of immunosuppressive therapy and without any evidenceof graft-versus-host disease (GVHD)

Exclusion Criteria:

• Participants may not have received any therapy with any investigational products,systemic anti-neoplastic therapy, or radiotherapy within 14 days prior to Cycle 1Day 1. Patients actively receiving hydroxyurea are eligible and may continue toreceive hydroxyurea during protocol treatment.

• Candidates for standard and/or potentially curative treatments.

• Major surgery within 28 days prior to Cycle 1 Day 1.

• New York Heart Association Class III or IV heart failure, myocardial infarctionwithin the past 6 months, unstable arrhythmia, or evidence of ischemia on anelectrocardiogram (EKG)

• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemictherapy

• Known, active HIV, Hepatitis A, B or C infection (prior Hepatitis C infection thathas been treated and determined to be cured is allowed)

• Symptomatic central nervous system (CNS) involvement with leukemia

• A concurrent second active and non-stable malignancy with the exception ofnon-melanoma skin cancer or carcinoma in-situ.