Study of C6 Ceramide NanoLiposome (CNL) in Patients With Relapsed/Refractory Acute Myeloid Leukemia (KNAN2001)

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

The study objective is to evaluate patient safety for patients with refractory and relapsed AML being treated with Ceramide NanoLiposome (CNL) .

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia, in Relapse; Acute Myeloid Leukemia, Refractory; Refractory/Relapse Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Ceramide NanoLiposome (Ceraxa)

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 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.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: James H Adair, Ph.D.; Phone Number: 814-360-4654; Email: jadair@pendreabio.com
• Study Contact Backup: Name: Bernadette M Adair, BS; Email: ba8387@gmail.com

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Recruiting
      • University of Virginia Cancer Center
      • Principal Investigator: Michael Keng, MD
      • Contact: Cory Caldwell; Phone Number: 434-297-4182; Email: CLCALMCRCs@uvahealth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open Label Administration of Ceramide NanoLiposome; Ceramide 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.	Drug: Ceramide NanoLiposome (Ceraxa); Ceramide NanoLiposome will be given by IV twice a week. The dose, which is based on body size, will be increased for the next group of patients if the first group of patients tolerates that dose and it will decrease for the next group if they do not tolerate the dose.; Other Names: Ceramide NanoLiposome

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients with Dose Limiting Toxicities as defined in Protocol Section 13.5	Dose Limiting Toxicities within the first cycle of CNL monotherapy. See section 13.5 of Protocol for the complete list of Dose Limiting Toxicities	At the end of the the first cycle of administration (each cycle is 28 days)
Number of Patients with Adverse Events	Number of Patients with Adverse Events	Through study completion, an average of 24 weeks
Severity of Adverse Events	Severity of Adverse Event As Described in Protocol	Through study completion, an average of 24 weeks
Duration of Adverse Events	Duration of Adverse Events, As Described in Protocol, measured in days	Length of Adverse Events as measured in days, measured through study completion, an average of 24 weeks
Duration of therapy	Duration of therapy provided as measured in days	Through study completion, an average of 24 weeks
Dose Levels achieved during study	Dose levels administered in milligrams per m2	Through study completion, an average of 24 weeks
Concentration Max (C Max)	Maximum Serum Concentration measured, in nanograms/milliliter	Through cycle one, 28 days (each cycle is 28 days)
Time to Maximum Study Drug (T Max)	Time to maximum concentration measured, in minutes	Through cycle one, 28 days (each cycle is 28 days)
Half Life of Study Drug	Time for drug to be reduced to half of the starting concentration (in minutes)	Through cycle one, 28 days (each cycle is 28 days)
Study Drug Clearance	The Amount of Study Drug Cleared per unit time (Nanograms/Minute)	Through cycle one, 28 days (each cycle is 28 days)
Ratio of C16/C24 Ceramides	Ratio of Ceramide 16 to Ceramide 24 (ng of C16/ng of C18) from bone marrow biopsy	After one cycle of therapy (Day 28)
Clinical Response - Complete Response	Complete Response	After Cycle Two (56 days)
Clinical Response - Complete Response with Incomplete Hematologic Recovery (CRi)	Complete Response with Incomplete Hematological Recovery as defined by blasts in bone marrow	After Cycle Two (56 days)
Clinical Response - Partial Remission	Partial Remission (as defined by blasts in bone marrow)	After Cycle Two (56 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients with Grade 3 or 4 Adverse Events	Grade 3 and 4 adverse events as defined by CTCAE v5.0	Through study completion, an average of 24 weeks
Overall Response	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	Through study completion, an average of 24 weeks, and up to 24 weeks afterwards (total of 48 weeks)
Event Free Survival	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	From registration to 24 weeks after completion of experimental drug treatment
Overall Survival	Overall survival (OS)	From registration to 24 weeks following drug administration
Quality of Life according to EORTC Quality of Life Questionnaire (QLQ) C30	Quality of life according to EORTC Quality of Life Questionnaire C30	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

Collaborators and Investigators

• Sponsor: Keystone Nano, Inc
• Collaborators: National Cancer Institute (NCI); Milton S. Hershey Medical Center; University of Virginia
• Investigators: Study Director: Daniel Vlock, MD, Keystone Nano, Inc; Study Chair: Christopher Prior, Ph.D., Keystone Nano

Publications and helpful links

General Publications

• Barth BM, Wang W, Toran PT, Fox TE, Annageldiyev C, Ondrasik RM, Keasey NR, Brown TJ, Devine VG, Sullivan EC, Cote AL, Papakotsi V, Tan SF, Shanmugavelandy SS, Deering TG, Needle DB, Stern ST, Zhu J, Liao J, Viny AD, Feith DJ, Levine RL, Wang HG, Loughran TP Jr, Sharma A, Kester M, Claxton DF. Sphingolipid metabolism determines the therapeutic efficacy of nanoliposomal ceramide in acute myeloid leukemia. Blood Adv. 2019 Sep 10;3(17):2598-2603. doi: 10.1182/bloodadvances.2018021295.
• Morad SAF, MacDougall MR, Abdelmageed N, Kao LP, Feith DJ, Tan SF, Kester M, Loughran TP Jr, Wang HG, Cabot MC. Pivotal role of mitophagy in response of acute myelogenous leukemia to a ceramide-tamoxifen-containing drug regimen. Exp Cell Res. 2019 Aug 15;381(2):256-264. doi: 10.1016/j.yexcr.2019.05.021. Epub 2019 May 18.
• Kester M, Bassler J, Fox TE, Carter CJ, Davidson JA, Parette MR. Preclinical development of a C6-ceramide NanoLiposome, a novel sphingolipid therapeutic. Biol Chem. 2015 Jun;396(6-7):737-47. doi: 10.1515/hsz-2015-0129.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: November 30, 2020
• First Submitted That Met QC Criteria: January 15, 2021
• First Posted (Actual): January 20, 2021

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Safety; Acute Myeloid Leukemia; Relapsed; Refractory; AML; Ceramide; NanoLiposome; CNL; Relapsed/Refratory Acute Myleoid Leukemia; NanoLiposomes; Ceraxa
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Leukemia, Myeloid, Acute
• Other Study ID Numbers: KNAN2001; 5R44CA275609-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Likely to be shared with PO1 Researchers at UVA and Penn State. In addition to yearly FDA reports, anticipate potential manuscripts as well but not yet decided with all participants.
• IPD Sharing Time Frame: Dec 1, 2026
• IPD Sharing Access Criteria: 6 months after Trial
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No