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

Trial Summary

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.

What data supports the effectiveness of the drug Selinexor in combination therapy for Acute Myeloid Leukemia?

Selinexor has shown promising activity in patients with acute myeloid leukemia (AML) both as a single agent and in combination with other treatments. In a phase 1 study, 43% of patients with relapsed or refractory AML responded to a combination of selinexor with other chemotherapy drugs, with some achieving complete remission. Additionally, selinexor has demonstrated anti-leukemia effects in preclinical studies, particularly when combined with other targeted therapies. ^{1 2 3 4 5}

Is Selinexor combination therapy safe for humans?

Selinexor has been studied in patients with acute myeloid leukemia and has shown some safety concerns. Common side effects include low blood cell counts, fatigue, and low sodium levels, but these were generally manageable with care. No dose-limiting toxicities were reported, suggesting it is generally safe when used as a single agent or in combination with other treatments. ^{1 2 3 4 5}

What makes the drug selinexor unique for treating acute myeloid leukemia?

Selinexor is unique because it is a first-in-class drug that works by blocking a protein called exportin 1, which helps cancer cells survive. This drug is used in combination with other treatments like cytarabine and daunorubicin to enhance its effectiveness against acute myeloid leukemia. ^{1 2 3 4 6}

What is the purpose of this trial?

This pilot phase II trial studies how well selinexor works when given together with induction, consolidation, and maintenance therapy in treating older patients with acute myeloid leukemia. Selinexor may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine and daunorubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Selinexor with induction, consolidation, and maintenance therapy may kill more cancer cells in older patients with acute myeloid leukemia.

Research Team

Timothy Pardee

Principal Investigator

Wake Forest University Health Sciences

Eligibility Criteria

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

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

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

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

References

1. United States 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. [2022]

2. England 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. [2022]

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

Phase 1 study of selinexor in combination with salvage chemotherapy in Adults with relapsed or refractory Acute myeloid leukemia. [2023]

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

A phase 1 clinical trial of single-agent selinexor in acute myeloid leukemia. [2021]

5. Italy 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. [2023]

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

Selinexor in combination with decitabine in patients with acute myeloid leukemia: results from a phase 1 study. [2021]