Study of C6 Ceramide NanoLiposome (CNL) in Patients With Relapsed/Refractory Acute Myeloid Leukemia

The research team has shown that C6 ceramide nanoliposome (CNL) has anti-cancer activity in laboratory models of AML and that when it is combined with other cancer-fighting drugs, it works better.

The primary goal of this study is to evaluate the safety of CNL given without other cancer treatments in patients with AML where either their initial treatment didn't work or it stopped working and the AML came back (refractory or relapsed AML, aka RR-AML). This study seeks to determine the right dose to start with in later studies when CNL is combined with other drugs in potential future studies.

CNL is given by intravenous (IV) infusion and will be given twice a week in this study. Participants will receive study treatment as long as it is considered safe for them to continue, though their disease status will be checked regularly to make sure that their disease has not gotten worse. Blood samples will be collected at many time-points to see how their bodies are responding to the drug and how long it stays in the blood.

The first patients in the study will start at one dose of the drug and, if that is shown to be safe, the next group will be treated at a slightly higher dose. Participants will be given CNL by intravenous (IV) infusion twice a week over about 2 hours and then they will be monitored for about 2 hours to make sure they don't have any bad side effects, but initially patients will be required to stay at the site for about 6 hours after the start of the infusion in order to get blood draws to see how long the drug stays active in their system.

Participants will have a bone marrow biopsy before their second "cycle" of drug (after about 1 month) and then again before their third cycle of drug in order to see how their disease is responding. After that, bone marrow biopsies will be about every other cycle based on what the study doctor recommends. If the doctor doesn't think that CNL is helping their disease, or if their doctor decides that it is not safe for them to continue, they will be taken off study treatment. Participants will be followed for safety and disease status for up to 6 months.

Inclusion criteria

• Signed informed consent is obtained prior to conducting any study-specific screening procedures.
• Willing and able to understand the nature of this study and to comply with the study and follow-up procedures.
• Age and Disease: ≥ 18 years of age with refractory or relapsed AML

Refractory AML: Patients who fail to achieve a complete remission (CR) or a complete remission with incomplete count recovery (CRi) after one or more ines of AML directed therapy.

Relapsed AML: Patients who achieved a complete remission (CR) or a complete remission with incomplete count recovery (CRi) with one or more prior lines of AML directed therapy but then developed a relapse of AML.

Note: Patients are eligible even if they have not received intensive induction chemotherapy but have been treated with other AML directed therapy like hypomethylating agents (azacitidine, decitabine).

• Eastern Cooperative Oncology Group (ECOG) performance status must be ≤2.
• ECOG performance status must be ≤2
• Peripheral white blood cell (WBC) count <30,000/µL. For cyto-reduction, the following are allowed to reduce WBC count to < 30,000/µL:

• hydroxyurea is allowed during screening and through the end of Cycle,
• cytarabine is allowed during screening but not after registration and should be limited 1 g/m2 or less from time of consent to registration.
• Adequate organ function as evidenced by the following laboratory findings:

• Total bilirubin ≤ 1.5 × upper limit of normal (ULN) or < 3 x ULN for patients with Gilbert-Meulengracht Syndrome
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN if not attributed to leukemia, or ≤ 5 x ULN if attributed to leukemia
• Creatinine clearance > 60 mL/min.

Exclusion criteria

Patients meeting any of the following criteria are ineligible for study entry:

• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmias not well controlled with medication, myocardial infarction within the previous 6 months before registration, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients may not be receiving any other concurrent investigational agents during study treatment and not for at least within one week prior to starting study treatment.
• Since the teratogenic potential of this combination is currently unknown, females who are pregnant or lactating are excluded.
• History of any other malignancies within the preceding 12 months before registration with the exception of in-situ cancer, non-muscle invasive bladder cancer, non-metastatic prostate cancer, basal or squamous cell skin cancer.
• Life-threatening illnesses other than AML, uncontrolled medical conditions or organ system dysfunction that, in the Investigator's opinion, could compromise the patient's safety or put the study outcomes at risk.
• Evidence of isolated extramedullary disease.
• Acute Promyelocytic Leukemia.
• AML with active central nervous system (CNS) involvement (as determined by study investigator).
• Severe infection requiring treatment that would interfere with study drug(s) or study participation in the opinion of the treating investigator.
• Past Hematopoietic stem cell transplant (HSCT) with graft vs host disease, immunosuppression other than low dose prednisone (10 mg) (or equivalent does of another immunosuppressant) within the 4 weeks before registration.
• All adverse reactions from prior therapy must have recovered to Grade ≤ 1 or acceptable baseline per treating investigator.