C6 ceramide nanoliposome (CNL) treatment for relapsed or refractory acute myeloid leukemia

Phase I Study of C6 Ceramide NanoLiposome (CNL) in Patients With Relapsed/Refractory Acute Myeloid Leukemia (RR-AML)

This will test whether C6 ceramide delivered in a nanoliposome (CNL) by IV is safe for adults whose acute myeloid leukemia has relapsed or not responded to prior treatment.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Keystone Nano, Inc (Industry-sponsored)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 1 site (Charlottesville, Virginia)
• Trial ID: NCT04716452 on ClinicalTrials.gov

What this trial studies

This is a Phase 1, open-label dose-escalation trial giving C6 ceramide in a nanoliposome (CNL) as a single agent to adults with relapsed or refractory AML to determine a safe dose for future combination studies. CNL is given by intravenous infusion twice weekly, with early patients observed longer after dosing and later patients observed for about two hours post-infusion. The study collects blood samples at multiple time points to measure how the drug behaves in the body and to monitor safety. Dose levels will be increased stepwise if prior doses are tolerated, and disease status will be checked regularly to ensure patient safety.

Who should consider this trial

Good fit: Adults (age ≥18) with relapsed or refractory AML who have ECOG performance status ≤2 and can tolerate frequent IV infusions and clinic visits are the intended candidates.

Not a fit: Patients who are candidates for standard curative therapies (for example immediate transplant) or who have poor performance status or significant organ dysfunction may not receive benefit from this Phase 1 investigational single-agent study.

Why it matters

Potential benefit: If successful, CNL could provide a new treatment option that controls disease and enables future combination therapies for patients with relapsed or refractory AML.

How similar studies have performed: Preclinical laboratory models showed anti-leukemia activity of C6 ceramide nanoliposomes and improved effects when combined with other drugs, but clinical experience in AML is very limited and this approach remains largely untested in patients.

Eligibility criteria

Inclusion Criteria:

1. Signed informed consent is obtained prior to conducting any study-specific screening procedures.
2. Willing and able to understand the nature of this study and to comply with the study and follow-up procedures.
3. 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).
4. Eastern Cooperative Oncology Group (ECOG) performance status must be ≤2.
5. ECOG performance status must be ≤2
6. 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.
7. 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:

1. 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.
2. 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.
3. Since the teratogenic potential of this combination is currently unknown, females who are pregnant or lactating are excluded.
4. 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.
5. 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.
6. Evidence of isolated extramedullary disease.
7. Acute Promyelocytic Leukemia.
8. AML with active central nervous system (CNS) involvement (as determined by study investigator).
9. Severe infection requiring treatment that would interfere with study drug(s) or study participation in the opinion of the treating investigator.
10. 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.
11. All adverse reactions from prior therapy must have recovered to Grade ≤ 1 or acceptable baseline per treating investigator.

Where this trial is running

Charlottesville, Virginia

• University of Virginia Cancer Center — Charlottesville, Virginia, United States (Recruiting)

Study contacts

• Study coordinator: James H Adair, Ph.D.

Conditions Acute Myeloid Leukemia, in Relapse; Acute Myeloid Leukemia, Refractory; Refractory/Relapse Acute Myeloid Leukemia; Acute Myeloid Leukemia; Relapsed; Refractory; Ceramide; AML