GSL Synthetase Inhibitor in Combination With Immune Checkpoint Inhibitor in Previously Treated Blood and Solid Tumor

NCT04944888 | Completed Phase 1 DMC

• 1 other identifier: CHN-PLAGH-BT-065
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

Immune checkpoint blockade has made great but unsatisfied success in treating cancers. One important reason is the hijacked HLA (Human Leukocyte Antigen) antigen presentation. Eliglustat could inhibit glycosphingolipids synthesis and restore HLA-I antigen presentation and transform the immunogenicity of tumor cells. Therefore,GSL synthetase inhibitor eliglustat in combination with immune checkpoint inhibitor may explore a new avenue for therapeutic intervention in cancer.

Conditions

Solid Tumor; Hematologic Malignancy

Keywords

GSL synthetase inhibitor; Immune checkpoint inhibitor; Solid tumor; Hematologic Malignancy

Outcome Measures

Primary Outcomes (1)

• Number of subjects occuring treatment related adverse events

  Determining the safety profile following the initiation of treatment and grading these toxicities by CTCAE v5.0

  Up to 90 days after the last dose of study drugs.

Secondary Outcomes (1)

• The percentage of enrolled patients that respond to the treatment

  Up to 120 days after the last dose of study drugs

Other Outcomes (2)

• Immunological response (cytokines, lymphocyte phenotype)

  Up to 120 days after the last dose of study drugs

• Biomarkers predictive of response and toxicity

  Up to 120 days after the last dose of study drugs

Study Arms (2)

Experimental Dose 1

EXPERIMENTAL

Eliglustat 84mg will be administered once daily in patients who are CYP2D6 ultra-rapid metabolizers (URMs), extensive metabolizers (EMs), intermediate metabolizers (IMs), or poor metabolizers (PMs), in the first 14 days and the following every other week until 24 weeks. For patients who still benefit from the trial, eliglustat 84mg will be daily administered every other week to 96 weeks. Immune checkpoint inhibitor (physician decided) will be administered intravenously on day 5 or day 15 every 3 weeks. For patients who still benefit from the trial, immune checkpoint inhibitor will be administered every 3 week to 96 weeks.

Drug: Eliglustat; Drug: Immune checkpoint inhibitor

Experimental Dose 2

EXPERIMENTAL

Eliglustat 84mg will be administered twice daily in patients who are CYP2D6 ultra-rapid metabolizers (URMs), extensive metabolizers (EMs), or intermediate metabolizers (IMs), or in the first 14 days and the following every other week until 24 weeks. For patients who still benefit from the trial, eliglustat 84mg will be administered twice daily every other week to 96 weeks. Immune checkpoint inhibitor (physician decided) will be administered intravenously on day 5 or day 15 every 3 weeks. For patients who still benefit from the trial, immune checkpoint inhibitor will be administered every 3 week to 96 weeks.

Drug: Eliglustat; Drug: Immune checkpoint inhibitor

Interventions

Eliglustat DRUG

Eliglustat will be given to enrolled patients at dose of 84mg daily (dose 1) , and then at dose of 84mg twice daily (dose 2).

Experimental Dose 1; Experimental Dose 2

Immune checkpoint inhibitor DRUG

immune checkpoint inhibitor (physician decided).

Experimental Dose 1; Experimental Dose 2

Eligibility Criteria

• Age: 16 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age from 16 to 75 years with estimated life expectancy \>3 months.
• Histopathological confirmed advanced or metastatic systematically pretreated solid tumors and relapsed/refractory hematological malignancies.
• Have at least one measurable target lesion for solid tumors.
• Fresh solid tumor samples or formalin-fixed paraffin embedded tumor archival samples within 3 months are necessary; Fresh tumor samples are preferred. Subjects are willing to accept tumor re-biopsy in the process of this study.
• Previous treatment must be completed for more than 4 weeks prior to the enrollment of this study, and subjects have recovered to \<= grade 1 toxicity.
• Have an Eastern Cooperative Oncology Group performance status (ECOG) of 0 or 2 at the time of enrollment.
• Have adequate organ function, which should be confirmed within 2 weeks prior to the first dose of study drugs.
• Previous treatment with anti-PD-1/PD-L1 antibodies or cytotoxic T lymphocyte associated antigen 4 (CTLA-4) inhibitors are allowed.
• Ability to understand and sign a written informed consent document.
• Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, and up to 90 days after the last dose of the drug.

You may not qualify if:

• Patients are unwilling to comply with the requirements of the protocol.
• The patient has documented prior esophageal varices or liver infarction or current liver enzymes (alanine transaminase, aspartate aminotransferase) or total bilirubin \>3 times the upper limit of normal.
• The patient is known to have any of the following: cardiac disease (congestive heart failure, recent acute myocardial infarction, bradycardia, heart block, ventricular arrhythmia), long QT syndrome, current treatment with Class IA or Class III antiarrhythmic medicinal products, interstitial lung disease of any grade or severely impaired pulmonary function.
• Uncontrolled intercurrent illness, including ongoing or active systemic infection or psychiatric illness/social situations and any other illness that would limit compliance with study requirements and jeopardize the safety of the patient.
• The patients is taking a CYP2D6 inhibitor and/or concomitantly with a strong or moderate CYP3A inhibitor.
• Active, known or suspected autoimmune diseases.
• Known brain metastases or active central nervous system (CNS). Subjects with CNS metastases who were treated with radiotherapy for at least 3 months prior to enrollment, have no central nervous symptoms and are off corticosteroids, are eligible for enrollment, but require a brain MRI screening.
• Patients are being treated with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
• History of severe hypersensitive reactions to other monoclonal antibodies.
• History of allergy or intolerance to study drug components.
• Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
• History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
• Pregnant or breast-feeding. Women of childbearing potential must have a pregnancy test performed within 7 days before the enrollment, and a negative result must be documented.
• Previous or concurrent cancer within 3 years prior to treatment start EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder tumors \[Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)\].
• Vaccination within 30 days of study enrollment.

Sponsors & Collaborators

• Chinese PLA General Hospital: lead

Study Sites (1)

Department of Biotherapeutic, Chinese PLA General Hospital

Beijing, China

Location

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

eliglustat; Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Weidong Han, PhD

  Biotherapeutic Department, Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Biotherapeutic Department

Study Record Dates

• First Submitted: June 23, 2021
• First Posted: June 30, 2021
• Study Start: July 1, 2021
• Primary Completion: November 30, 2023
• Study Completion: November 30, 2023
• Last Updated: December 19, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)