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

NCT04716452 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: KNAN20015R44CA275609-02
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Acute Myeloid Leukemia, Refractory; Refractory/Relapse Acute Myeloid Leukemia; Acute Myeloid Leukemia, in Relapse

Keywords

Acute Myeloid Leukemia; Relapsed; Refractory; Ceramide; AML; NanoLiposome; Relapsed/Refratory Acute Myleoid Leukemia; NanoLiposomes; Safety; CNL; Ceraxa

Outcome Measures

Primary Outcomes (14)

• 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 Outcomes (5)

• Number of Patients with Grade 3 or 4 Adverse Events

  Through study completion, an average of 24 weeks

• Overall Response

  Through study completion, an average of 24 weeks, and up to 24 weeks afterwards (total of 48 weeks)

• Event Free Survival

  From registration to 24 weeks after completion of experimental drug treatment

• Overall Survival

  From registration to 24 weeks following drug administration

• Quality of Life according to EORTC Quality of Life Questionnaire (QLQ) 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

Study Arms (1)

Open Label Administration of Ceramide NanoLiposome

EXPERIMENTAL

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)

Interventions

Ceramide NanoLiposome (Ceraxa) DRUG

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.

Also known as: Ceramide NanoLiposome

Open Label Administration of Ceramide NanoLiposome

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Keystone Nano, Inc: lead
• Milton S. Hershey Medical Center: collaborator
• National Cancer Institute (NCI): collaborator
• University of Virginia: collaborator

Study Sites (1)

University of Virginia Cancer Center

Charlottesville, Virginia, 22903, United States

RECRUITING

Related Publications (3)

• 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.

  PMID: 31488436 BACKGROUND

• 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.

  PMID: 31112736 BACKGROUND

• 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.

  PMID: 25838296 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Daniel Vlock, MD

  Keystone Nano, Inc

  STUDY DIRECTOR

• Christopher Prior, Ph.D.

  Keystone Nano

  STUDY CHAIR

Central Study Contacts

James H Adair, Ph.D.

CONTACT

814-360-4654; jadair@pendreabio.com

Bernadette M Adair, BS

CONTACT

ba8387@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single group assignment

Study Record Dates

• First Submitted: November 30, 2020
• First Posted: January 20, 2021
• Study Start: October 1, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Dec 1, 2026
• Access Criteria: 6 months after Trial

Locations

US (1)