Myelodysplastic SyndromesPhase 1/2NCT05918055
Eltanexor (KPT-8602) With Inqovi (Decitabine-Cedazuridine) in High-Risk Myelodysplastic Syndromes
A Phase 1/2 study testing KPT-8602, Inqovi and Bone marrow aspirate in people with Myelodysplastic Syndromes, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Myelodysplastic Syndromes
- What is being tested?
- KPT-8602, Inqovi and Bone marrow aspirate
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Nov 2023to 12 Mar 2025
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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).
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: A Phase I/II Trial of Eltanexor (KPT-8602) With Inqovi (Decitabine-Cedazuridine) in High-Risk Myelodysplastic Syndromes
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.
Read more
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.
Read the detailed description
Background:
- The myelodysplastic syndromes (MDS) are a group of clonal bone marrow neoplasms characterized by ineffective hematopoiesis, cytopenia, and high risk of transformation to acute myeloid leukemia (AML).
- The median survival of patients with newly diagnosed higher-risk MDS (HR-MDS) according to the Revised International Prognostic Scoring System (IPSS-R) is 1.5 years.
- Hypomethylating agents (HMAs), such as azacitidine and decitabine, are the standard of care therapy for HR-MDS. However, less than half of patients respond to HMAs, and even the best responses are transient and non-curative.
- The only curative treatment for patients with MDS is allogeneic hematopoietic stem cell transplantation (HSCT); however, only a small portion are eligible for transplant.
- More effective therapies are needed for patients with HR-MDS.
- A promising approach for improving HMA efficacy in the treatment of MDS is by exploiting therapeutic synergism in combinatorial approaches.
- Inqovi (decitabine-cedazuridine) is an oral formulation of decitabine plus cytidine deaminase inhibitor that was recently Food and Drug Administration (FDA)-approved for MDS, based on a similar safety and efficacy profile to decitabine for injection.
- KPT-8602 (eltanexor) is an orally available, second-generation selective inhibitor of nuclear export (SINE) that covalently binds to exportin 1 (XPO1).
- XPO1 is a protein that mediates the nuclear export of molecules from the nucleus to the cytoplasm of the cell. Among affected molecules are tumor suppressor genes, messenger ribonucleic acid (mRNAs) encoding oncogenes (including cellular myelocytomatosis oncogene (c-MYC), and newly assembled ribosomal subunits.
- By interfering with c-MYC translation, KPT-8602 may diminish rebound methylation after decitabine cessation and improve treatment responses in patients with MDS.
- Preliminary reports from a Phase 1/2 trial of KPT-8602 monotherapy in patients with higher-risk MDS who have failed HMAs show anti-tumor activity and an acceptable toxicity profile.
- Sequential addition of KPT-8602 to Inqovi may improve treatment responses in patients with MDS by acting synergistically to inhibit further DNA methylation.
Objective:
- Phase I: To determine the recommended phase 2 dose (RP2D) of KPT-8602 in combination with Inqovi in adult participants with higher-risk MDS
- Phase II: To determine overall response rate (ORR) of KPT-8602 in combination with Inqovi in adult participants with higher- risk MDS
Eligibility:
- Participants must have histologically or cytologically confirmed MDS according to 2016 World Health Organization (WHO) criteria, and for both Phase I and II:
- have 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 PR or experienced disease progression prior to completing 4 cycles)
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status <= 2 (KPS >= 60)
Design:
- Participants with HR-MDS will be enrolled in both Phase I and II.
- Participants will be treated with Inqovi at a fixed dose of 1 tablet (35 mg decitabine and 100 mg cedazuridine) daily on Days 1-5 of each 28-day cycle, followed by KPT-8602 at escalating doses (Phase I) or the RP2D (Phase II).
- In Phase I, KPT-8602 will be dose-escalated following a standard 3+3 design, with a starting dose level of 10 mg for 10 days (staggered) within a cycle. If tolerated, the dose will be escalated to 14 days per cycle, or dose de-escalated to 5 mg at 14 or 10 days.
- This study will be done at the National Institutes of Health (NIH) Center with an enrollment of up to 80 planned participants.
- Conditions
- Myelodysplastic Syndromes
- Being tested
- KPT-8602, Inqovi, Bone marrow aspirate, Bone marrow biopsy, ECG
- Keywords
- Acute Myeloid Leukemia, hypomethylating agents, Allogeneic Hematopoietic Stem Cell Transplantation
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KPT-8602Drug
Also called Eltanexor
5-10 mg by mouth (PO) daily for 10-14 days based on dose level
InqoviDrug
Also called Decitabine, Cedazuridine
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.
Bone marrow aspirateProcedure or surgery
Also called BM aspirate
Screening (if necessary), baseline (30 days prior to treatment start), and Cycle 1, Day 28 (phase I only).
Bone marrow biopsyProcedure or surgery
Also called BM biopsy
Screening (if necessary), baseline (30 days prior to treatment start), and Cycle 1, Day 28 (phase I only).
ECGDiagnostic test
Also called Electrocardiogram
Screening and baseline. Cycle 1, Day 1 and Cycle 1, Day 15 (2 hours post dose that day +/- 20 minutes).
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: Drug: KPT-8602; Drug: Inqovi; Procedure: Bone marrow aspirate; Procedure: Bone marrow biopsy; Diagnostic Test: ECG |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 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.
Measured: 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)
AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Measured: 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)
The half-life of Eltanexor (KPT-8602) will be evaluated in participants, by dose level when given in combination with Inqovi. Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half.
Measured: 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)
Steady state concentration, measured by the Eltanexor (KPT-8602) blood concentration will be evaluated in participants, by dose level when given in combination with Inqovi (Decitabine-Cedazuridine). Steady state is defined as consistent drug concentration in the body.
Measured: 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)
The grades and types of toxicity noted for the agent at each dose level will be reported. Toxicity was assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). 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.
Measured: 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
A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Serious adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).
Measured: At least weekly through cycle 3 and then at the start and every cycle after that
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2023
- Study start14 Nov 2023
- Primary completion10 Mar 2025
- Study completion12 Mar 2025
Why it stopped: Drug company withdrew support.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Najla El Jurdi, National Cancer Institute (NCI)
- Investigators
- Najla El Jurdi, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05918055
- Sponsor's protocol ID
- 10001541
- Other IDs
- 001541-C
- Status last verified
- Nov 2025
- First submitted
- 23 Jun 2023
- Last updated
- 2 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All collected individual participant data (IPD) will be shared. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).