What side effects are associated with this type of intervention?

Common treatments for Myelodysplastic Syndrome (MDS) include hypomethylating agents such as decitabine and azacitidine, and selective inhibitors of nuclear export like KPT-8602. The known side effects of decitabine and azacitidine include febrile neutropenia, thrombocytopenia, anemia, and gastrointestinal symptoms such as nausea and diarrhea. KPT-8602, being a selective inhibitor of nuclear export, may cause side effects like fatigue, nausea, and cytopenias. These side effects are important considerations when evaluating treatment options for MDS.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Myelodysplastic Syndrome (MDS). Notably, Decitabine and Azacitidine are hypomethylating agents that inhibit DNA methylation and have been widely used in MDS treatment. Inqovi, a combination of Decitabine and Cedazuridine, was approved to enhance the bioavailability of Decitabine by inhibiting its degradation. Additionally, Venetoclax, often used in combination with hypomethylating agents, has shown efficacy in MDS. These treatments aim to modify the disease course and improve patient outcomes by targeting the underlying pathophysiology of MDS.

What other types of research exist?

Promising novel alternatives for MDS treatment in 2024 include: 1) Venetoclax in combination with hypomethylating agents (HMAs) like azacitidine or decitabine, which has shown efficacy in elderly patients with AML and high-risk MDS. 2) Ivosidenib combined with azacitidine for patients with IDH1-mutated MDS, demonstrating good overall response rates and tolerability. 3) Gilteritinib combined with azacitidine for patients with FLT3-mutated MDS, showing improved overall response rates in preliminary trials. These alternatives offer new avenues for treatment and may provide better outcomes for MDS patients.

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Eltanexor + Inqovi for Myelodysplastic Syndrome

Phase 1 & 2

Recruiting

Led By Steven Z Pavletic, M.D.

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

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

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug combination (KPT-8602 and Inqovi) for adults with severe blood disease (high-risk MDS) who haven't improved with standard treatments. Inqovi stops cancer cell growth, while KPT-8602 blocks a protein that helps cancer cells survive.

Who is the study for?

Adults over 18 with high-risk Myelodysplastic Syndromes (MDS) that didn't improve after treatment can join. They need to be fairly active, have good organ function, and not pregnant or breastfeeding. Participants must agree to use birth control and have no recent growth factor treatments or uncontrolled illnesses.

What is being tested?

The trial is testing Eltanexor (KPT-8602) combined with Inqovi (Decitabine-Cedazuridine), both oral tablets for MDS. Over at least six 28-day cycles, participants take these drugs at home and visit the clinic regularly for exams and tests like blood work and bone marrow biopsies.

What are the potential side effects?

Possible side effects of KPT-8602 and Inqovi include digestive issues, changes in blood cell counts leading to anemia or infection risk, liver problems, fatigue, heart rhythm changes. Specific side effects will vary by individual.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ each cycle (bloods), cycle 2 and 6 during treatment and every 3-6 months (bloods and bone marrow)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~each cycle (bloods), cycle 2 and 6 during treatment and every 3-6 months (bloods and bone marrow)

This trial's timeline: 3 weeks for screening, Varies for treatment, and each cycle (bloods), cycle 2 and 6 during treatment and every 3-6 months (bloods and bone marrow) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase 1: To determine the recommended phase 2 dose (RP2D) of KPT-8602 in combination with Inqovi in adult participants with with higher-MDS

Phase 2: To determine the overall response rate (ORR) of KPT-8602 in combination with Inqovi in adult participants with with higher-MDS

Secondary study objectives

Phase 1: To characterize the PK properties of KPT-8602 in combination with Inqovi in MDS participants

Phase 2: To further evaluate the PK properties and safety of KPT-8602 in combination with Inqovi in MDS participants

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Phase II- Dose expansion for HR-MDSExperimental Treatment2 Interventions

Inqovi for 5 days, followed by RP2D/Phase II dose of KPT-8602

Group II: Phase I- Dose escalation of KPT-8602 for HR-MDSExperimental Treatment2 Interventions

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

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Myelodysplastic Syndrome (MDS) include Selective Inhibitors of Nuclear Export (SINE) and hypomethylating agents. SINE, such as KPT-8602, work by inhibiting the export of tumor suppressor proteins from the nucleus, thereby promoting apoptosis of malignant cells. Hypomethylating agents like Decitabine, which is part of Inqovi, inhibit DNA methylation, leading to the reactivation of tumor suppressor genes and induction of cell differentiation and apoptosis. Cedazuridine, combined with Decitabine in Inqovi, increases the bioavailability of Decitabine by inhibiting its degradation. These mechanisms are crucial for MDS patients as they target the underlying genetic and epigenetic abnormalities, potentially improving blood cell counts and reducing the progression to acute myeloid leukemia.