Eltanexor (KPT-8602) With Inqovi (Decitabine-Cedazuridine) in High-Risk Myelodysplastic Syndromes

NCT05918055 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 10001541001541-C
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Myelodysplastic syndromes (MDS) are diseases that affect the bone marrow. They can inhibit the blood formation process and reduce blood cell counts. High-risk MDS can lead to leukemia. People with high-risk MDS have a low survival rate. Better treatments are needed. Objective: To test a study drug Eltanexor (KPT-8602), combined with another drug (Inqovi), in people with MDS. Eligibility: Adults aged 18 years and older with high-risk MDS that did not respond to treatment. Design: Participants will be screened. They will have a physical exam. They will have blood and urine tests and tests of their heart function. They may have a bone marrow biopsy: Their hip will be numbed; then a needle will be inserted to draw out a sample of soft tissue from inside the bone. They will answer questions about their quality of life. Genetic tests may be performed. KPT-8602 and Inqovi are both tablets taken by mouth. Participants will take these drugs at home on a 28-day cycle. They will take Inqovi once a day on days 1 to 5. They will take KPT-8602 on a schedule assigned by the researcher. Participants will be given a drug diary to record each dose. Participants will visit the clinic for an exam at least once in each cycle. Some tests, including the bone marrow biopsy, may be repeated. Participants will continue treatment for at least 6 cycles. If their disease improves, they may continue taking the drugs after 6 cycles. Participants will have follow-up visits at the clinic for about 8 years.

Conditions

Myelodysplastic Syndromes

Keywords

Acute Myeloid Leukemia; hypomethylating agents; Allogeneic Hematopoietic Stem Cell Transplantation

Outcome Measures

Primary Outcomes (3)

• Phase 1: Recommended Phase 2 Dose (RP2D) of Eltanexor (KPT-8602) in Combination With Inqovi (Decitabine-Cedazuridine) in Adult Participants With Higher-Myelodysplastic Syndromes (MDS)

  If no DLTs are observed at the highest planned dose level for evaluation (dose level 2), dose escalation will stop, and this will be considered the recommended phase 2 dose (RP2D) of Eltanexor (KPT-8602). A DLT is defined as a treatment-related toxicity based on Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.

  From day 1 of study drug through 28 days after the first dose

• Phase 1: Number of Participants Who Have Grades 3 and/or 4 Dose-limiting Toxicity (DLT) at the Recommended Phase 2 Dose (RP2D)

  Participants enrolled in phase I will have the grades and types of toxicity reported at each dose level to determine the RP2D. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event. Toxicity was assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).

  First 28 days of study treatment

• Phase 2: Overall Response Rate (ORR) of Eltanexor (KPT-8602) in Combination With Inqovi (Decitabine-Cedazuridine) Reported With a 95% Confidence Interval in Adult Participants With Higher-Myelodysplastic Syndromes (MDS)

  Participants evaluated in phase II will have the fraction with clinical responses reported, with a 95% confidence interval. ORR is defined as Complete Remission (CR)+Partial Remission (PR)+marrow (mCR) with hematologic improvement (HI) per each cohort and assessed by the 2006 International Working Group Response Criteria with Modified Definitions for Hematologic Improvement by the 2018 International Working Group Response Criteria. Complete Remission (CR) is bone marrow: ≤5% myeloblasts with normal maturation of all cell lines. Partial Remission (PR) is all CR criteria if abnormal before treatment except bone marrow blasts decreased by ≥50% over pretreatment but still \>5%; and cellularity and morphology not relevant. Marrow Complete Remission is bone marrow: ≤5% myeloblasts and decrease by ≥50% over pretreatment.

  Each cycle (bloods), cycle 2 and 6 during treatment and every 3-6 months (bloods and bone marrow)

Secondary Outcomes (5)

• Phase 1: AUC Under the Concentration Time Curve (AUC 0-48h) of Eltanexor (KPT-8602) in Combination With Inqovi (Decitabine-Cedazuridine) in Participants With Myelodysplastic Syndromes (MDS)

  1, 2, 3, 4, 8, 24 and 48 hours after the product administration on days 8 and 21 of cycle one

• Phase 1: Half-life of Eltanexor (KPT-8602) in Combination With Inqovi (Decitabine-Cedazuridine) in Participants With Myelodysplastic Syndromes (MDS)

  1, 2, 3, 4, 8, 24 and 48 hours after the product administration on days 8 and 21 of cycle one

• Phase 1: Calculating Steady State (Css) Concentration of Eltanexor (KPT-8602) When Given in Combination With Inqovi (Decitabine-Cedazuridine)

  1, 2, 3, 4, 8, 24 and 48 hours after the product administration on days 8 and 21 of cycle one

• Phase 2: Number of Grades 1, 2, 3, 4, and/or 5 Toxicity of Eltanexor (KPT-8602) and Inqovi (Decitabine-Cedazuridine) at Each Dose Level in Participants With Myelodysplastic Syndromes (MDS)

  At least weekly through cycle 3 and then at the start and every cycle after that

• Phase 2: Number of Serious Adverse Events Leading to Discontinuation, Death, and Laboratory Abnormalities

  At least weekly through cycle 3 and then at the start and every cycle after that

Other Outcomes (1)

• Phase 1: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).

  From the first study intervention through 30 days after the study agent (s) was/were administered, an average of 8.5 months.

Study Arms (2)

Phase I- Dose escalation of Eltanexor (KPT-8602) for High-Risk Myelodysplastic Syndromes

EXPERIMENTAL

Inqovi for 5 days, followed by escalating doses of Eltanexor (KPT-8602)

Drug: KPT-8602; Drug: Inqovi; Procedure: Bone marrow aspirate; Procedure: Bone marrow biopsy; Diagnostic Test: ECG

Phase II- Dose expansion for High-Risk Myelodysplastic Syndromes

EXPERIMENTAL

Inqovi for 5 days, followed by recommended phase 2 dose (RP2D)/Phase II dose of Eltanexor (KPT-8602)

Drug: KPT-8602; Drug: Inqovi; Procedure: Bone marrow aspirate; Procedure: Bone marrow biopsy; Diagnostic Test: ECG

Interventions

KPT-8602 DRUG

5-10 mg by mouth (PO) daily for 10-14 days based on dose level

Also known as: Eltanexor

Phase I- Dose escalation of Eltanexor (KPT-8602) for High-Risk Myelodysplastic Syndromes; Phase II- Dose expansion for High-Risk Myelodysplastic Syndromes

Inqovi DRUG

Inqovi will be administered via oral route once daily on Days 1-5 of each treatment cycle, according to guidelines outlined in the Food and Drug Administration (FDA) product label.

Also known as: Decitabine, Cedazuridine

Phase I- Dose escalation of Eltanexor (KPT-8602) for High-Risk Myelodysplastic Syndromes; Phase II- Dose expansion for High-Risk Myelodysplastic Syndromes

Bone marrow aspirate PROCEDURE

Screening (if necessary), baseline (30 days prior to treatment start), and Cycle 1, Day 28 (phase I only).

Also known as: BM aspirate

Phase I- Dose escalation of Eltanexor (KPT-8602) for High-Risk Myelodysplastic Syndromes; Phase II- Dose expansion for High-Risk Myelodysplastic Syndromes

Bone marrow biopsy PROCEDURE

Screening (if necessary), baseline (30 days prior to treatment start), and Cycle 1, Day 28 (phase I only).

Also known as: BM biopsy

Phase I- Dose escalation of Eltanexor (KPT-8602) for High-Risk Myelodysplastic Syndromes; Phase II- Dose expansion for High-Risk Myelodysplastic Syndromes

ECG DIAGNOSTIC_TEST

Screening and baseline. Cycle 1, Day 1 and Cycle 1, Day 15 (2 hours post dose that day +/- 20 minutes).

Also known as: Electrocardiogram

Phase I- Dose escalation of Eltanexor (KPT-8602) for High-Risk Myelodysplastic Syndromes; Phase II- Dose expansion for High-Risk Myelodysplastic Syndromes

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically or cytologically confirmed Myelodysplastic Syndromes (MDS) by the Laboratory of Pathology, NCI- according to 2016 World Health Organization (WHO) criteria AND:
• Cohort 1 (Phase 1) \& 2 (Phase 2): have high-risk Myelodysplastic Syndromes (HR-MDS) Revised International Prognostic Scoring System (IPSS-R \> 3.5) with inadequate response to hypomethylating agent (HMA) therapy \[(received \>= 4 cycles of the standard dose (35 mg decitabine and 100 mg cedazuridine) without prior dose reductions, with failure to achieve at least a partial remission (PR) or experienced disease progression prior to completing 4 cycles)
• Age \>=18 years
• Eastern Cooperative Oncology Group (ECOG) performance status \<= 2 (Karnofsky \>= 60%,)
• Participants must have adequate organ and marrow function as defined below:
• total bilirubin \<= 1.5 X institutional upper limit of normal
• \<= 3 X institutional upper limit of normal in participants with Gilbert's syndrome (except for participants with increased bilirubin levels attributed to intramedullary hemolysis, which will be allowable)
• Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT)/alanine transaminase (ALT) serum glutamic pyruvic transaminase (SGPT) \<= 3 X institutional upper limit of normal
• \<= 5 X institutional upper limit of normal if related to MDS-specific cause
• creatinine clearance (by Cockcroft-Gault) \>= 60 mL/min/1.73m\^2
• corrected QT interval using the Fridericia formula (QTc(F) \<= 470 ms
• Individuals of child-bearing potential (IOCBP) must have a negative serum test at screening. IOCBP is defined as the following:
• Has not undergone a hysterectomy, tubal ligation, or bilateral oophorectomy
• Has not been naturally postmenopausal for at least 24 consecutive months (i.e.,has had menses at any time in the preceding 24 consecutive months).
• Individuals of childbearing potential (IOCBP) as well as those able to father a child with an individual able to become pregnant potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) unless they have had a prior vasectomy, hysterectomy, or bilateral oophorectomy, prior to study entry, for the duration of study participation, and for at least 6 months after last dose of HMA.

You may not qualify if:

• Participants with platelet transfusion-refractory thrombocytopenia, with inability to keep platelet threshold above 10K/mcL with transfusions or those with ongoing or uncontrolled hemorrhagic complications.
• Participants with clinically significant neutropenia, defined as absolute neutrophil count (ANC) \<100 cells/mcL with frequent hospitalizations for infection (average \> 1 hospitalization per month in the past 6 months).
• Participants on treatment with a myeloid growth factor (e.g., granulocyte colony-stimulating factor (G-CSF) within 14 days prior to initiation of study treatment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to HMAs, or other agents used in study.
• Uncontrolled intercurrent illness evaluated by history, physical exam, and chemistries or situations that would limit compliance with study requirements, interpretation of results or that could increase risk to the participant
• Participants with the following cardiac conditions: symptomatic congestive heart failure, unstable angina pectoris, or uncontrolled cardiac arrhythmia as assessed by electrocardiogram (ECG).
• Pregnancy (confirmed with Beta-human chorionic gonadatropin (HCG) serum or urine pregnancy test performed in individuals of childbearing potential at screening)
• Presence of any other malignancy (except basal and squamous cell carcinoma of the skin, or stable chronic cancers on hormone or targeted therapy) for which participant received systemic anticancer treatment (except maintenance therapy) within 24 months prior to treatment.
• Participants with active/uncontrolled Hepatitis B
• Participants with active/uncontrolled Hepatitis C
• Participants with active/uncontrolled human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
• Participants currently taking contraindicated medications for HIV, Hepatitis B, or Hepatitis C disease control

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Interventions

Eltanexor; decitabine and cedazuridine drug combination; Decitabine; cedazuridine; Electrocardiography

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis

Results Point of Contact

• Title: Dr. Najla El Jurdi
• Organization: National Cancer Institute

najla.eljurdi@nih.gov

240-992-4033

Study Officials

• Najla El Jurdi, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 23, 2023
• First Posted: June 26, 2023
• Study Start: November 14, 2023
• Primary Completion: March 10, 2025
• Study Completion: March 12, 2025
• Last Updated: December 2, 2025
• Results First Posted: December 2, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Data from this study may be requested by contacting the principal investigator (PI).

Locations

US (1)