Selinexor + Choline Salicylate for Lymphoma and Multiple Myeloma

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must not be taking: Anticoagulants, Aspirin, Warfarin

Disqualifiers: Active hepatitis, Uncontrolled illness, others

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

Compensation: Varies

Number of Visits: 1

Duration: 24-48 weeks

39 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase Ib trial evaluates the side effects and best dose of choline salicylate given together with a low dose of selinexor in treating patients with non-Hodgkin or Hodgkin lymphoma, or multiple myeloma whose prior treatment did not help their cancer (refractory) or for patients with histiocytic/dendritic cell neoplasm. Anti-inflammatory drugs, such as choline salicylate lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Selinexor may stop the growth of cancer cells by blocking a protein called CRM1 that is needed for cell growth. This trial may help doctors learn more about selinexor and choline salicylate as a treatment for with non-Hodgkin or Hodgkin lymphoma, histiocytic/dendritic cell neoplasm, multiple myeloma.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are on active anticoagulant therapy with certain medications like direct oral anticoagulants, aspirin, or warfarin, you may not be eligible, except for low-dose aspirin (81 mg) for heart disease prevention, which must be paused during the trial.

Is the combination of Selinexor and Choline Salicylate safe for humans?

Choline salicylate has been shown to inhibit platelet aggregation (clumping of blood cells) in studies with mice, which suggests it may affect blood clotting. However, specific safety data for the combination of Selinexor and Choline Salicylate in humans is not provided in the available research. ^{1 2 3 4 5}

What makes the drug Selinexor unique for treating lymphoma and multiple myeloma?

Selinexor is unique because it is an oral drug that targets a novel pathway by inhibiting exportin-1 (XPO1), a protein responsible for transporting tumor-suppressor proteins out of the cell nucleus, which is overexpressed in multiple myeloma. This mechanism offers a new treatment option for relapsed or refractory multiple myeloma, especially in combination with other drugs like dexamethasone and bortezomib. ^{6 7 8 9 10}

Research Team

Jonas Paludo

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

Adults with certain types of blood cancers like non-Hodgkin or Hodgkin lymphoma, multiple myeloma, or histiocytic/dendritic cell neoplasm that haven't responded to previous treatments. Participants must be over 18, not pregnant, able to consent and follow-up, provide samples for research, have a specific level of disease severity and physical fitness (ECOG 0-2), and meet certain blood count criteria.

Inclusion Criteria

You have a disease that can be measured or assessed according to specific guidelines.

Willingness to provide mandatory blood specimens and tissue samples for correlative research

I am not pregnant.

Exclusion Criteria

I haven't had cancer treatment like radiation or chemotherapy in the last 2 weeks.

I have had a heart attack in the last 6 months or have heart failure needing ongoing treatment.

Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive selinexor orally twice a week and choline salicylate three times daily for up to 6 cycles, with the possibility of extending to 12 cycles if stable disease is achieved

24-48 weeks

Visits on days 1, 3, 8, 10, 15, 17, 22, and 24 of each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Choline Salicylate
• Selinexor

Trial Overview The trial is testing the combination of low-dose Selinexor with Choline Salicylate in patients whose cancer hasn't improved after prior treatment. It aims to find the safest dose while assessing how well these drugs work together against various types of lymphomas and multiple myeloma.

Participant Groups

Group I: Treatment (selinexor, choline salicylate) Experimental Treatment 2 Interventions

Patients receive selinexor PO BIW on days 1, 3, 8, 10, 15, 17, 22, and 24, and choline salicylate PO TID on days 1-28. Patients undergoing pharmacokinetic analysis receive choline salicylate beginning on D3C1 and beginning on day 1 of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patents who achieve \>= stable disease continue treatment for an additional 6 cycles (maximum of 12 cycles) at the discretion of the treating physician and patient.

Choline Salicylate is already approved in United States, Canada for the following indications:

Approved in United States as Choline salicylate for:

• Anti-inflammatory

Approved in Canada as Choline salicylate for:

• Anti-inflammatory

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Karyopharm Therapeutics

Collaborator

Trials

1

Recruited

40+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Choline salicylate was found to be the most effective drug in inhibiting ADP-induced platelet aggregation in vivo, ex vivo, and in vitro, suggesting its potential as a strong anti-platelet agent.

In addition to its anti-platelet effects, choline salicylate showed a tendency to reduce mortality in mice injected with endotoxin, indicating possible protective effects against severe infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Anti-platelet actions of salicylates: in vivo, ex vivo and in vitro effects of choline salicylate]. Irino, O., Saitoh, K., Ohkubo, K.[2019]

NC-1300-O-3 effectively prevents gastric lesions in rats at doses of 3 and 10 mg/kg, showing consistent efficacy even after 4 weeks of repeated administration, indicating its potential as a long-term protective treatment.

The cytoprotective effect of NC-1300-O-3 operates independently of gastric acid secretion and involves endogenous sulfhydryl compounds, as it remains effective even when gastric secretion is inhibited by omeprazole.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytoprotective effect of NC-1300-O-3 against gastric lesions induced by necrotizing agents in rats. Matsukura, H., Masuda, M., Kawaguchi, K., et al.[2019]

NCX-4016, a nitric oxide-releasing aspirin, does not cause gastric damage or inflammation, unlike traditional aspirin, making it a safer alternative for patients, especially those on selective COX-2 inhibitors.

In contrast to aspirin, NCX-4016 does not trigger the synthesis of protective aspirin-triggered lipoxin (ATL) or upregulate gastric COX-2 expression, indicating a different mechanism of action that avoids gastric injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspirin, but not NO-releasing aspirin (NCX-4016), interacts with selective COX-2 inhibitors to aggravate gastric damage and inflammation. Wallace, JL., Zamuner, SR., McKnight, W., et al.[2017]

Aspirin was found to be the most effective at reducing the production of prostacyclin (PGI2) and thromboxane A2 (TXA2) in the heart after an infarction, indicating its strong impact on these important cardiovascular markers.

Both celecoxib and NCX-4016 showed similar myocardial effects, but they operate through different mechanisms, suggesting potential alternatives to aspirin that may have less gastric toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of cyclooxygenase-2 inhibitor (celecoxib) on the infarcted heart in situ. Yamamoto, T., Kakar, NR., Vina, ER., et al.[2017]

TEI-9090 and its active form TEI-7165 effectively inhibit platelet aggregation and adhesion in a dose-dependent manner, showing comparable or superior effects to established anti-platelet agents like PGI2 and PGE1.

TEI-9090 and TEI-7165 not only inhibit platelet aggregation but also enhance platelet disaggregation, suggesting their potential as potent anti-platelet drugs with a mechanism that may be beneficial in preventing blood clots.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-platelet effects of isocarbacyclin methyl ester on human and rabbit platelets in vitro. Inoue, K., Aoki, Y., Kitahara, S., et al.[2014]

Selinexor, an inhibitor of the exportin 1 (XPO1) receptor, showed significant cytotoxic activity against various solid tumors and acute lymphoblastic leukemia (ALL) xenografts in a study involving in vitro and in vivo testing, with 76% of solid tumor models and 63% of ALL models showing improved event-free survival.

The treatment resulted in objective responses in 4 out of 38 solid tumor xenografts and 25% of ALL xenografts, indicating its potential effectiveness, particularly in tumors with specific genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamic and genomic markers associated with response to the XPO1/CRM1 inhibitor selinexor (KPT-330): A report from the pediatric preclinical testing program. Attiyeh, EF., Maris, JM., Lock, R., et al.[2023]

Selinexor, an exportin-1 inhibitor, has received regulatory approval for treating multiple myeloma and non-Hodgkin lymphomas based on pivotal trials, including the SADAL and BOSTON trials, demonstrating its potential as a monotherapy or in combination regimens.

While selinexor shows promise in overcoming treatment resistance and may have synergistic effects with other therapies, it has consistent tolerability issues, necessitating improved management strategies to enhance its efficacy compared to newer cellular and immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor therapy for multiple myeloma and non-Hodgkin lymphomas. Goldsmith, SR., Liu, L., Shiah, K.[2023]

Selinexor is an oral medication that targets exportin-1 (XPO1), which is overexpressed in multiple myeloma, and has shown significant anti-myeloma effects in preclinical studies, both alone and in combination with other treatments.

Selinexor-based therapies have been approved for treating relapsed/refractory multiple myeloma, including specific combinations like selinexor-dexamethasone for advanced cases, demonstrating its efficacy in patients who have undergone multiple prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor: Targeting a novel pathway in multiple myeloma. Mo, CC., Yee, AJ., Midha, S., et al.[2023]

Selinexor, a first-in-class selective inhibitor of nuclear export (XPO1), has shown significant efficacy in treating relapsed refractory multiple myeloma (RRMM), leading to its FDA approval in combination with dexamethasone based on results from the pivotal phase II STORM trial.

The phase III BOSTON trial demonstrated that selinexor combined with bortezomib and dexamethasone is superior to the standard treatment of bortezomib and dexamethasone alone, although it is associated with a predictable toxicity profile that requires careful management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Nuclear Export Proteins in Multiple Myeloma Therapy. Richard, S., Jagannath, S.[2022]

Selinexor, when used in combination with dexamethasone or bortezomib and dexamethasone, showed an overall response rate of 29.5% in 44 patients with relapsed or refractory myeloma, indicating its efficacy as a treatment option.

The most common side effects included fatigue and thrombocytopenia, with 56% of patients requiring dose reductions; however, these adjustments did not negatively impact progression-free survival, suggesting that selinexor can be managed safely in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real World Efficacy and Toxicity of Selinexor: Importance of Patient Characteristics, Dose Intensity and Post Progression Outcomes. Kastritis, E., Gavriatopoulou, M., Solia, E., et al.[2023]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[Anti-platelet actions of salicylates: in vivo, ex vivo and in vitro effects of choline salicylate]. [2019]

2. Japan pubmed.ncbi.nlm.nih.gov

Cytoprotective effect of NC-1300-O-3 against gastric lesions induced by necrotizing agents in rats. [2019]

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

Aspirin, but not NO-releasing aspirin (NCX-4016), interacts with selective COX-2 inhibitors to aggravate gastric damage and inflammation. [2017]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of cyclooxygenase-2 inhibitor (celecoxib) on the infarcted heart in situ. [2017]

5. Germany pubmed.ncbi.nlm.nih.gov

Anti-platelet effects of isocarbacyclin methyl ester on human and rabbit platelets in vitro. [2014]

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

Pharmacodynamic and genomic markers associated with response to the XPO1/CRM1 inhibitor selinexor (KPT-330): A report from the pediatric preclinical testing program. [2023]

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

Selinexor therapy for multiple myeloma and non-Hodgkin lymphomas. [2023]

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

Selinexor: Targeting a novel pathway in multiple myeloma. [2023]

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

Targeting Nuclear Export Proteins in Multiple Myeloma Therapy. [2022]

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

Real World Efficacy and Toxicity of Selinexor: Importance of Patient Characteristics, Dose Intensity and Post Progression Outcomes. [2023]