Eltanexor + Inqovi for Myelodysplastic Syndrome

Overseen by Steven Z Pavletic, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: National Cancer Institute (NCI)

Must not be taking: Myeloid growth factors

Disqualifiers: Thrombocytopenia, Neutropenia, Cardiac conditions, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, any prior therapy must be completed more than 4 weeks before starting the trial, except for Inqovi. Please consult with the trial team for specific guidance.

What data supports the effectiveness of the drug Inqovi for treating Myelodysplastic Syndrome?

Inqovi, a combination of decitabine and cedazuridine, has been shown to be effective for treating Myelodysplastic Syndrome (MDS) with clinical studies reporting complete remission rates of 21% and 18% in different trials, and similar effectiveness to intravenous decitabine. The drug was approved by the FDA based on these findings. ^{1 2 3 4 5}

Is the combination of Eltanexor and Inqovi safe for treating myelodysplastic syndrome?

Inqovi, a combination of decitabine and cedazuridine, has been studied for safety in treating myelodysplastic syndromes. Common serious side effects include low white blood cell counts (neutropenia), low platelet counts (thrombocytopenia), and fever with low white blood cell counts (febrile neutropenia). These side effects are similar to those seen with intravenous decitabine. ^{1 3 4 5 6}

What makes the drug Eltanexor + Inqovi unique for treating myelodysplastic syndrome?

Eltanexor + Inqovi is unique because it combines an oral fixed-dose of decitabine and cedazuridine, which allows for effective oral administration by preventing the breakdown of decitabine in the body, with Eltanexor, an investigational oral drug that targets nuclear export in cells, offering a novel approach for patients who are resistant to other treatments. ^{1 2 3 4 7}

Research Team

Steven Z Pavletic, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

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.

Inclusion Criteria

I have high-risk MDS and my previous treatment with HMA didn't work well.

- AST(SGOT)/ALT(SGPT) <= 3 X institutional upper limit of normal OR <= 5 X institutional upper limit of normal if related to MDS-specific cause

My organs and bone marrow work well.

Exclusion Criteria

I have not had any other cancer in the last 2 years.

I have active or uncontrolled Hepatitis C.

My low platelet count does not improve with transfusions.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive KPT-8602 and Inqovi in 28-day cycles, with Inqovi taken daily on days 1-5 and KPT-8602 on a schedule assigned by the researcher

6 cycles (approximately 6 months)

At least 1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 years

Follow-up visits at the clinic

Extension

Participants may continue taking the drugs if their disease improves after 6 cycles

Treatment Details

Interventions

• Inqovi (Other)
• KPT-8602 (Other)

Trial Overview 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.

Participant Groups

Group I: Phase II- Dose expansion for HR-MDS Experimental Treatment 2 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-MDS Experimental Treatment 2 Interventions

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

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Inqovi, a combination of decitabine and cedazuridine, was approved by the FDA for treating myelodysplastic syndromes (MDS) based on a phase III study involving 133 adults, showing similar effectiveness to intravenous decitabine.

The treatment demonstrated a complete remission rate of 21% in one study and 18% in another, with a median duration of remission lasting around 7.5 to 8.7 months, while adverse reactions were consistent with those seen in IV decitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Decitabine and Cedazuridine Tablets for Myelodysplastic Syndromes. Kim, N., Norsworthy, KJ., Subramaniam, S., et al.[2023]

A new oral drug combination, DEC-cedazuridine (C-DEC), has been developed to provide a more convenient treatment option for patients with myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML), which traditionally required lengthy parenteral therapies.

C-DEC has been approved by major health authorities, including the US FDA, for patients with newly diagnosed or previously treated intermediate or high-risk MDS and CMML, indicating its safety and potential efficacy in managing these complex disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of cedazuridine/decitabine in the management of myelodysplastic syndrome and chronic myelomonocytic leukemia. Thota, S., Oganesian, A., Azab, M., et al.[2021]

The fixed-dose oral combination of decitabine and cedazuridine (Inqovi®) has been approved for treating myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML), enhancing the oral bioavailability of decitabine through the inhibition of cytidine deaminase by cedazuridine.

Decitabine is already an established treatment for MDS and CMML, and the combination therapy has shown promise in ongoing clinical studies for other cancers like acute myeloid leukaemia (AML), glioma, and solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine/Cedazuridine: First Approval. Dhillon, S.[2021]

Luspatercept has shown significant efficacy in treating low-risk myelodysplastic syndromes (MDS), with 63% of patients experiencing hematological improvement and 38% achieving transfusion independence in clinical trials.

Oral decitabine combined with oral cedazuridine has demonstrated pharmacological equivalence to intravenous decitabine, achieving overall response rates of 60% and 43% in phase 2 and 3 trials for high-risk MDS, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New treatment for myelodysplastic syndromes: luspatercept and oral hypomethylating agents]. Usuki, K.[2022]

The phase 2 study found that oral cedazuridine/decitabine (100 mg/35 mg) provided similar systemic exposure and DNA demethylation compared to standard IV decitabine (20 mg/m2) in patients with myelodysplastic syndromes or chronic myelomonocytic leukemia, indicating comparable efficacy.

Clinical responses were observed in 60% of patients, with 21% achieving a complete response, while the most common serious side effects included neutropenia (46%) and thrombocytopenia (38%), highlighting the treatment's safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. Garcia-Manero, G., Griffiths, EA., Steensma, DP., et al.[2021]

In a study of 99 patients with myelodysplastic syndromes (MDS), decitabine administered at a higher dose of 20 mg/m² daily for 5 days every 4 weeks resulted in a 32% overall response rate, indicating significant efficacy in treating MDS.

The outpatient regimen of decitabine not only provided comparable efficacy to the FDA-approved inpatient schedule but also allowed for more than half of the patients to show clinical improvement, suggesting a safe and effective alternative treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter study of decitabine administered daily for 5 days every 4 weeks to adults with myelodysplastic syndromes: the alternative dosing for outpatient treatment (ADOPT) trial. Steensma, DP., Baer, MR., Slack, JL., et al.[2023]

In a phase 1/2 clinical trial involving 20 patients with higher-risk myelodysplastic syndromes (MDS) who were refractory to hypomethylating agents, the investigational drug eltanexor demonstrated a 53.3% overall response rate, with 46.7% of patients achieving complete remission.

Eltanexor was found to be safe and well tolerated, with the most common side effects being nausea, diarrhea, and fatigue, while the median overall survival for patients evaluated for efficacy was approximately 9.86 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral eltanexor treatment of patients with higher-risk myelodysplastic syndrome refractory to hypomethylating agents. Lee, S., Mohan, S., Knupp, J., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Decitabine and Cedazuridine Tablets for Myelodysplastic Syndromes. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Role of cedazuridine/decitabine in the management of myelodysplastic syndrome and chronic myelomonocytic leukemia. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Decitabine/Cedazuridine: First Approval. [2021]

4. Japan pubmed.ncbi.nlm.nih.gov

[New treatment for myelodysplastic syndromes: luspatercept and oral hypomethylating agents]. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Multicenter study of decitabine administered daily for 5 days every 4 weeks to adults with myelodysplastic syndromes: the alternative dosing for outpatient treatment (ADOPT) trial. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Oral eltanexor treatment of patients with higher-risk myelodysplastic syndrome refractory to hypomethylating agents. [2022]