Clinical Trials /

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



The study explores whether Ceramide NanoLiposome (CNL) combined with other conventional cancer-fighting drugs makes them work better.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Not yet recruiting


Phase 1

Trial Eligibility



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

Clinical Trial IDs

  • NCT ID: NCT04716452


  • Acute Myeloid Leukemia, in Relapse
  • Acute Myeloid Leukemia, Refractory


Ceramide NanoLiposome (Ceraxa)Ceramide NanoLiposomeOpen Label Administration of Ceramide NanoLiposome


The study explores whether Ceramide NanoLiposome (CNL) combined with other conventional cancer-fighting drugs makes them work better.

Detailed Description

      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 your AML came back (refractory or relapsed AML, or RR-AML). This study
      seeks to determine the right dose to start with in later studies when CNL is combined with
      other drugs.

      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 in order 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,
      of 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

Trial Arms

Open Label Administration of Ceramide NanoLiposomeExperimentalCeramide NanoLiposome will be administered by Intravenous Dosing twice per week in accordance with the protocol relative to dose escalation. There is no placebo group or arm of the study.
  • Ceramide NanoLiposome (Ceraxa)

Eligibility Criteria

        Inclusion Criteria:

          1. Signed informed consent is obtained prior to conducting any study-specific screening

          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) after one line
             of AML directed therapy

             Relapsed AML: Patients who achieved a complete remission (CR) 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. Peripheral white blood cell (WBC) count <30,000/µL. For cyto-reduction, hydroxyurea is
             allowed during screening and through Cycle 2, Day 3 to reduce WBC count to < 30,000

          6. 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) ≤ 2.5 × ULN

               -  Creatinine clearance > 60 mL/min

          7. QT-interval corrected according to Fridericia's formula (QTcF) < 450 ms on one
             electrocardiogram (ECG) at screening

        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, or have
             received any investigational agent within one week of registration.

          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, prostate,
             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 or AML with active central nervous system (CNS)

          8. Untreated severe (in the opinion of the treating investigator) infection

          9. Active and uncontrolled infection with HIV (viral load is detectable by PCR)

         10. Active infection with Hepatitis B virus (HbSAg positive or PCR with detectable viral
             load) or Hepatitis C virus (viral load detectable by PCR).

         11. Past Hematopoietic stem cell transplant (HSCT) with active graft vs host disease,
             immunosuppression other than low dose prednisone (5 mg), or calcineurin inhibitors
             within the 4 weeks before registration
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Patients with Dose Limiting Toxicities as defined in Protocol Section 13.5
Time Frame:At the end of the the first cycle of administration (each cycle is 28 days)
Safety Issue:
Description:Dose Limiting Toxicities within the first cycle of CNL monotherapy. See section 13.5 of Protocol for the complete list of Dose Limiting Toxicities

Secondary Outcome Measures

Measure:Number of Patients with Grade 3 or 4 Adverse Events
Time Frame:Through study completion, an average of 24 weeks
Safety Issue:
Description:Grade 3 and 4 adverse events as defined by CTCAE v5.0
Measure:Overall Response
Time Frame:Through study completion, an average of 24 weeks, and up to 24 weeks afterwards (total of 48 weeks)
Safety Issue:
Description:Overall response of CNL monotherapy in patients with RR-AML: Complete remission (CR) + Complete remission with incomplete count recovery (CRi) + partial response (PR). CR, CRi and PR as defined as European LeukemiaNet 2017 (ELN 2017) response criteria
Measure:Event Free Survival
Time Frame:From registration to 24 weeks after completion of experimental drug treatment
Safety Issue:
Description:Event-free survival (EFS): the time from registration until documented refractory disease, relapse after achieving CR/CRi, or death from any cause, whichever is observed first
Measure:Overall Survival
Time Frame:From registration to 24 weeks following drug administration
Safety Issue:
Description:Overall survival (OS)
Measure:Quality of Life according to EORTC Quality of Life Questionnaire (QLQ) C30
Time Frame:Prior to starting study treatment, on day 1 of each cycle (each cycle is 28 days), and at end of treatment (which is expected to be 2 to 3 months (cycles) for most patients
Safety Issue:
Description:Quality of life according to EORTC Quality of Life Questionnaire C30


Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Keystone Nano, Inc

Trial Keywords

  • Acute Myeloid Leukemia
  • Relapsed
  • Refractory
  • Ceramide
  • AML
  • NanoLiposome

Last Updated

January 20, 2021