Selinexor Combination Therapy for Acute Myeloid Leukemia

Recruiting at 1 trial location

Overseen By Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Wake Forest University Health Sciences

Disqualifiers: Secondary AML, Active malignancy, CNS involvement, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

64 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether selinexor, combined with standard chemotherapy drugs, can more effectively treat older patients with acute myeloid leukemia (AML). Selinexor blocks enzymes that help cancer cells grow. The trial includes two groups: one receives only standard chemotherapy (such as Cytarabine and Daunorubicin Hydrochloride), while the other receives standard treatment plus selinexor. People with newly diagnosed AML who haven't had significant prior treatment might be suitable candidates. Participants should not have certain genetic mutations or previous specific types of leukemia. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, it allows the use of hydroxyurea, cytarabine, or ATRA before starting the trial treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that selinexor, when combined with other treatments, has been studied for its safety and effectiveness in treating acute myeloid leukemia (AML). In past studies, selinexor was used with other drugs and was generally well-tolerated by patients. Common side effects include tiredness, nausea, and low blood counts, similar to those seen with many cancer treatments.

While some patients have experienced side effects, these are usually manageable with medical assistance. The combination of selinexor with other treatments has shown promise in managing AML, and its safety is considered acceptable for cancer treatment.

Selinexor is also approved by the FDA for other conditions, which adds confidence in its safety. However, as with any new treatment, participating in a clinical trial involves close monitoring to ensure patient safety and manage any potential side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the investigational treatment for Acute Myeloid Leukemia (AML) because it includes Selinexor, which represents a novel approach. Unlike the standard treatments, which typically involve cytarabine and daunorubicin, Selinexor works by inhibiting a protein called XPO1, which plays a role in cancer cell survival. This mechanism could potentially enhance the effectiveness of traditional chemotherapy. Additionally, Selinexor is taken orally, offering a different and possibly more convenient method of administration compared to standard intravenous treatments. This combination of a new target and delivery method is what makes this treatment stand out in the fight against AML.

What evidence suggests that this trial's treatments could be effective for acute myeloid leukemia?

Research has shown that selinexor, when combined with common chemotherapy drugs like cytarabine and daunorubicin, may help treat acute myeloid leukemia (AML). In this trial, one group will receive the standard treatment of cytarabine and daunorubicin, while another group will receive selinexor with these drugs. Studies have found that adding selinexor to usual AML treatments can improve patient response. This combination has demonstrated better results in both newly diagnosed and relapsed AML patients. Selinexor works by blocking certain enzymes that aid cancer cell growth, potentially leading to better patient outcomes. Although more research is needed, early findings suggest this combination could be more effective than standard treatments alone. ^{2 5 6 7 8}

Who Is on the Research Team?

Timothy Pardee

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

This trial is for adults over 18 with newly diagnosed Acute Myeloid Leukemia (non-APL) who haven't had AML treatment, except Hydrea and ATRA. It's not for those with certain genetic abnormalities or previous cancer treatments, HIV, hepatitis, CNS involvement, or other serious health issues. Participants must be physically able to undergo therapy and willing to use effective contraception.

Inclusion Criteria

I have a new diagnosis of Acute Myeloid Leukemia and haven't started treatment, except possibly Hydrea or ATRA.

I am taking hydroxyurea or cytarabine for leukocytosis without severe side effects.

Ability to understand and the willingness to sign an IRB-approved informed consent document.

Exclusion Criteria

I cannot swallow pills or have a condition affecting how my body absorbs medication.

Psychiatric illness/social situations that would limit compliance with study requirements.

I have another cancer that needs treatment, not including skin cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Patients receive cytarabine IV on days 1-7, daunorubicin hydrochloride IV on days 1-3, and selinexor PO twice weekly from day 1. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

2 weeks

Re-Induction Therapy

Patients whose disease has not responded receive cytarabine IV on days 1-5, daunorubicin hydrochloride IV on days 1-2, and selinexor PO twice weekly. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

2 weeks

Consolidation Therapy

Patients in remission receive cytarabine IV every 12 hours on days 1-3, and selinexor PO twice weekly from day 1. Treatment repeats every 42 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Up to 18 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Cytarabine
• Daunorubicin Hydrochloride
• Selinexor

Trial Overview The trial tests Selinexor combined with chemotherapy drugs cytarabine and daunorubicin hydrochloride in older patients. The goal is to see if this mix can better kill leukemia cells by blocking enzymes needed for cell growth while stopping the cells from dividing or spreading.

How Is the Trial Designed?

Group I: Arm 2 (Selinexor) cytarabine, daunorubicin and selinexor Experimental Treatment 3 Interventions

INDUCTION: Cytarabine IV on days 1-7, daunorubicin hydrochloride IV on days 1-3, and selinexor PO twice weekly from day 1. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity. RE-INDUCTION: Disease has not responded receive cytarabine IV on days 1-5, daunorubicin hydrochloride IV on days 1-2, and selinexor PO twice weekly. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: In remission receive cytarabine IV every 12 hours for a total 6 doses days 1-3, and selinexor PO twice weekly from day 1. Treatment repeats every 42 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Group II: Standard of Care - Cytarabine and daunorubicin Active Control 2 Interventions

INDUCTION: Cytarabine IV on days 1-7, daunorubicin hydrochloride IV on days 1-3. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity. RE-INDUCTION: Disease has not responded receive cytarabine IV on days 1-5, daunorubicin hydrochloride IV on days 1-2. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: In remission receive cytarabine IV every 12 hours for a total 6 doses days 1-3. Treatment repeats every 42 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Cytarabine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Cytosar-U for:

• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Chronic myeloid leukemia
• Meningeal leukemia

Approved in European Union as Depocyt for:

• Lymphomatous meningitis

Approved in Canada as Cytosar-U for:

• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Chronic myeloid leukemia

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase 1 study involving 23 patients with relapsed/refractory acute myeloid leukemia (AML), the combination of selinexor with mitoxantrone, etoposide, and cytarabine showed an overall response rate of 43%, with 26% of patients achieving complete remission.

The maximum tolerated dose of selinexor was determined to be 30 mg/m2 due to dose-limiting side effects, including hyponatremia, indicating that while the treatment is promising, careful monitoring for toxicity is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of selinexor in combination with salvage chemotherapy in Adults with relapsed or refractory Acute myeloid leukemia. Bhatnagar, B., Zhao, Q., Mims, AS., et al.[2023]

Selinexor, a selective inhibitor of nuclear export, was found to be safe and well-tolerated in a phase 1 study involving 95 patients with relapsed or refractory acute myeloid leukemia (AML), with manageable side effects primarily being mild gastrointestinal and constitutional toxicities.

The study showed that 14% of evaluable patients achieved an objective response, leading to significantly improved progression-free survival (5.1 months vs. 1.3 months) and overall survival (9.7 months vs. 2.7 months) compared to nonresponders, indicating its potential efficacy as a treatment for AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 clinical trial of single-agent selinexor in acute myeloid leukemia. Garzon, R., Savona, M., Baz, R., et al.[2021]

The combination of selinexor (targeting XPO1) and sorafenib (targeting FLT3) shows significant anti-leukemia effects in FLT3-mutated acute myeloid leukemia, with pre-clinical studies demonstrating marked cell killing and differentiation without immediate toxicity.

In a phase IB clinical trial, this combination therapy resulted in complete or partial remissions in 6 out of 14 patients with refractory acute myeloid leukemia, suggesting a promising new treatment strategy for patients who have not responded to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combinatorial targeting of XPO1 and FLT3 exerts synergistic anti-leukemia effects through induction of differentiation and apoptosis in FLT3-mutated acute myeloid leukemias: from concept to clinical trial. Zhang, W., Ly, C., Ishizawa, J., et al.[2023]

In a phase I study involving 25 older and relapsed or refractory AML patients, the combination of the oral exportin-1 inhibitor selinexor and decitabine showed a 40% overall response rate, indicating preliminary clinical activity.

The recommended dose of selinexor was established at 60 mg twice weekly, with manageable safety concerns, including significant but tolerable side effects like hyponatremia and febrile neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor in combination with decitabine in patients with acute myeloid leukemia: results from a phase 1 study. Bhatnagar, B., Zhao, Q., Mims, AS., et al.[2021]

In a phase I trial involving 20 patients with acute myeloid leukemia (AML), the combination of selinexor with high-dose cytarabine and mitoxantrone was found to be feasible and tolerable, with no dose-limiting toxicities observed at the target dose of 80 mg.

The treatment resulted in a 70% overall response rate, with 50% of patients achieving complete remission, indicating promising efficacy for selinexor in combination therapy for AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of selinexor in combination with high-dose cytarabine and mitoxantrone for remission induction in patients with acute myeloid leukemia. Wang, AY., Weiner, H., Green, M., et al.[2022]

In a phase II study involving 175 patients aged 60 and older with relapsed/refractory acute myeloid leukemia, selinexor did not significantly improve overall survival compared to physician's choice treatment, with median survival times of 3.2 months versus 5.6 months.

Patients treated with selinexor experienced a higher incidence of serious adverse events, including thrombocytopenia and febrile neutropenia, indicating a need for careful patient selection and monitoring in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 2:1 randomized, open-label, phase II study of selinexor vs. physician's choice in older patients with relapsed or refractory acute myeloid leukemia. Sweet, K., Bhatnagar, B., Döhner, H., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5524530/

A phase 1 clinical trial of single-agent selinexor in acute ... These findings suggest that selinexor is safe as a monotherapy in patients with relapsed or refractory AML and have informed subsequent phase 2 clinical ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02088541

Selinexor (KPT-330) in Older Patients With Relapsed AML This is a randomized, multicenter, open-label, phase 2 study of the SINE compound, selinexor given orally versus specified investigator choices.

3. jnccn.org jnccn.org/view/journals/jnccn/22/2.5/article-CLO24-083.xml

CLO24-083: Efficacy of Selinexor in Acute Myeloid Leukemia Conclusion: Selinexor has shown promising results in both ND and R/R AML patients. Selinexor, in combination with standard regimens, showed superior response ...

4. investors.karyopharm.com investors.karyopharm.com/2020-12-07-Karyopharm-Announces-Presentation-of-New-XPOVIO-R-Selinexor-Data-in-Patients-with-Acute-Myeloid-Leukemia-at-the-American-Society-of-Hematology-2020-Annual-Meeting

Karyopharm Announces Presentation of New XPOVIO ... "AML is the most common form of acute leukemia in adults and unfortunately, very little improvement has been made in recent years in terms of ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8663856/

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Safety Study of the Selective Inhibitor of Nuclear Export ... A total of 286 participants were enrolled out of which 1 participants with MM never treated due to disease progression prior to dose initiation and 285 ...

7. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1602911/full

Selinexor in acute myeloid leukemia: therapeutic ... This part will focus on the choice and clinical outcomes of selinexor combination therapies with various drugs for AML. For specific data, refer to Table 2.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0147027224000175

Efficacy and safety of selinexor for patients with relapsed ... Selinexor is more effective when used in combination with corticosteroids and PIs compared to when used alone. It is effective in both relapsed and refractory ...