Selinexor for Diffuse Large B-Cell Lymphoma

Recruiting at 13 trial locations

Overseen By Karyopharm Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Karyopharm Therapeutics Inc

Must not be taking: Strong CYP3A inhibitors, inducers

Disqualifiers: Pregnancy, PMBL, Active infections, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 16

244 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are taking strong CYP3A inhibitors or inducers, you may need to stop them 7 to 14 days before starting the trial.

What data supports the effectiveness of the drug Selinexor for treating diffuse large B-cell lymphoma?

Selinexor has shown promising results in treating various types of non-Hodgkin lymphoma, including diffuse large B-cell lymphoma, with 31% of patients experiencing significant tumor reduction. It has also been effective in other cancers, like multiple myeloma, indicating its potential as a cancer treatment. ^{1 2 3 4 5}

Is selinexor generally safe for humans?

Selinexor has been tested in humans for various cancers, including non-Hodgkin lymphoma and gynecological malignancies. Common side effects include low blood cell counts (thrombocytopenia, neutropenia, anemia, leukopenia), fatigue, and low sodium levels (hyponatremia). Despite these side effects, it has been considered safe at certain doses, such as 35 mg/m2, in clinical trials. ^{2 3 4 6 7}

What makes the drug Selinexor unique for treating diffuse large B-cell lymphoma?

Selinexor is unique because it is the first oral drug that selectively inhibits nuclear export, offering a new mechanism of action for treating diffuse large B-cell lymphoma, especially in patients who have not responded to other treatments. It addresses an unmet need for those with relapsed or refractory cases, providing a novel option when other therapies have failed. ^{1 8 9 10 11}

What is the purpose of this trial?

A multicenter, open-label Phase 2b study of selinexor (KPT-330) in participants with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who have no therapeutic options of demonstrated clinical benefit.

Research Team

Michael Kauffman, MD, PhD

Principal Investigator

Karyopharm Therapeutics Inc

Sharon Shacham, PhD

Principal Investigator

Karyopharm Therapeutics Inc

Reshma Rangwala, MD, PhD

Principal Investigator

Karyopharm Therapeutics Inc

Eligibility Criteria

Adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who have tried at least two but no more than five previous treatments, including an anthracycline-based chemotherapy and anti-CD20 immunotherapy. Participants must not be eligible for stem cell transplant, should have measurable disease, adequate organ function, and a life expectancy over three months. Pregnant or breastfeeding women are excluded.

Inclusion Criteria

I have been previously diagnosed with DLBCL, either as a new condition or transformed from an indolent lymphoma.

Written informed consent in accordance with federal, local, and institutional guidelines. The participant must provide informed consent prior to the first screening procedure.

Estimated life expectancy > 3 months at study entry.

Exclusion Criteria

I have ongoing complications from a stem cell transplant.

I can swallow pills and don't have issues absorbing medication.

My cancer has spread to my brain or its coverings.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive a fixed dose of 60 mg selinexor orally twice weekly for 4-week cycles until disease progression or intolerance

Variable (until disease progression or intolerance)

8 doses per 4-week cycle

Treatment Part 2

Participants are randomized to receive either 40 mg or 60 mg selinexor orally twice weekly for 4-week cycles until disease progression

Variable (until disease progression)

8 doses per 4-week cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

Treatment Details

Interventions

• Selinexor

Trial Overview The trial is testing Selinexor (KPT-330), a potential treatment for those with DLBCL that has returned or resisted other treatments. This Phase 2b study will evaluate the drug's effectiveness in patients who lack other beneficial treatment options.

Participant Groups

Group I: Part 2: Arm B-Selinexor 60 mg Experimental Treatment 1 Intervention

Participants received selinexor 60 mg orally BIW on Days 1 and 3 of each week of 4-week treatment cycles) for 2 cycles (each cycle of 28 days) followed by 60 mg once weekly (QW) in the subsequent cycles until disease progression (total of 8 doses per cycle).

Group II: Part 2: Arm A-Selinexor 40 mg Experimental Treatment 1 Intervention

Participants received selinexor 40 mg orally BIW on Days 1 and 3 of each week of 4-week treatment cycles (28 days) until disease progression (total of 8 doses per cycle).

Group III: Part 1: Selinexor 60 mg Experimental Treatment 1 Intervention

Participants received fixed dose of 60 mg selinexor orally, twice weekly (BIW) on Days 1 and 3 (e.g., Monday and Wednesday or Tuesday and Thursday, etc.) of Weeks 1-4 of each four week (each cycle of 28 days) cycle (total of 8 doses per cycle).

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

Approved in United States as Xpovio for:

• Multiple myeloma
• Diffuse large B-cell lymphoma

Approved in Canada as Xpovio for:

• Multiple myeloma

Who Is Running the Clinical Trial?

Karyopharm Therapeutics Inc

Lead Sponsor

Trials

89

Recruited

7,200+

Richard Paulson

Karyopharm Therapeutics Inc

Chief Executive Officer since 2021

MBA from the University of Toronto's Rotman School of Management

Reshma Rangwala

Karyopharm Therapeutics Inc

Chief Medical Officer since 2023

MD, PhD

Findings from Research

Selinexor, the first exportin inhibitor, has shown a 28% overall response rate in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) after at least two lines of therapy, with a median duration of response of 9.3 months.

The drug has a favorable safety profile, primarily causing hematological and digestive side effects, and does not require dose adjustments for patients with kidney or liver issues, making it a viable option for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A drug profile on selinexor for the treatment of refractory diffuse large B-cell lymphoma. Sylvain, C.[2022]

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]

In a phase 1 trial involving 79 patients with relapsed or refractory non-Hodgkin lymphoma, selinexor demonstrated a safety profile with common side effects including thrombocytopenia and neutropenia, but it was well-tolerated overall.

Selinexor showed promising efficacy, with 31% of evaluable patients achieving objective responses, including 4 complete responses, indicating that it may be a viable treatment option for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective inhibition of nuclear export with selinexor in patients with non-Hodgkin lymphoma. Kuruvilla, J., Savona, M., Baz, R., et al.[2021]

Selinexor (XPOVIO™) is a novel oral medication that inhibits Exportin-1 (XPO1) and has been approved for treating relapsed or refractory multiple myeloma (RRMM) in adults, marking a significant advancement in cancer therapy.

The drug is currently being tested for effectiveness in various other types of blood and solid tumors, indicating its potential as a versatile treatment option in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor: First Global Approval. Syed, YY.[2023]

In a phase 2 trial involving 114 patients with heavily pretreated recurrent gynecological cancers, selinexor showed a disease control rate of 30%, indicating its potential effectiveness as a treatment option for ovarian and endometrial cancers.

Common side effects included thrombocytopenia and fatigue, but these were manageable and reversible, with lower-grade adverse events observed in patients receiving a once-weekly dosing schedule compared to twice-weekly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study of the Exportin 1 inhibitor selinexor in patients with recurrent gynecological malignancies. Vergote, IB., Lund, B., Peen, U., et al.[2023]

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]

Selinexor is the only clinically validated oral selective inhibitor of nuclear export (SINE) and has been approved for treating relapsed/refractory diffuse large B-cell lymphoma, showing promise in addressing cases where chemotherapy fails.

The article reviews Selinexor's anti-tumor mechanisms and its potential applications in non-Hodgkin lymphoma (NHL), highlighting the need for new effective treatments for patients with poor responses to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The Latest Research Progress of Selinexor in the Treatment of Non-Hodgkin Lymphoma --Review]. Tang, XY., Wang, Y., Xu, RR.[2023]

In a phase 2b study involving 127 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), the oral drug selinexor demonstrated an overall response rate of 28%, with 12% achieving a complete response and 17% a partial response, indicating its potential efficacy as a treatment option.

Selinexor was found to have a manageable safety profile, with the most common severe side effects being thrombocytopenia and neutropenia, but no treatment-related deaths were reported, suggesting it could be a viable non-cytotoxic alternative for patients with limited options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial. Kalakonda, N., Maerevoet, M., Cavallo, F., et al.[2023]

Selinexor, an oral medication for diffuse large B-cell lymphoma (DLBCL), showed consistent efficacy in heavily pretreated patients, with no significant differences in overall response rate or duration of response based on various patient characteristics.

Younger patients (under 65) and those with higher lymphocyte counts had significantly longer overall survival, while the most common side effects were thrombocytopenia and nausea, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Association between Patient Characteristics and the Efficacy and Safety of Selinexor in Diffuse Large B-Cell Lymphoma in the SADAL Study. Zijlstra, JM., Follows, G., Casasnovas, RO., et al.[2022]

Selinexor is a novel oral therapy that selectively inhibits nuclear export and has received fast track designation from the FDA for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL), indicating its potential efficacy in this challenging condition.

While selinexor shows promise, further translational studies are needed to understand its mechanism of action and to identify which genetic subtypes of DLBCL may benefit most from this treatment, as well as to explore its use in combination with standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor (KTP-330) - a selective inhibitor of nuclear export (SINE): anti-tumor activity in diffuse large B-cell lymphoma (DLBCL). Ben-Barouch, S., Kuruvilla, J.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

A drug profile on selinexor for the treatment of refractory diffuse large B-cell lymphoma. [2022]

2. 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]

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

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

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

Selective inhibition of nuclear export with selinexor in patients with non-Hodgkin lymphoma. [2021]

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

Selinexor: First Global Approval. [2023]

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

Phase 2 study of the Exportin 1 inhibitor selinexor in patients with recurrent gynecological malignancies. [2023]

7. 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]

8. China pubmed.ncbi.nlm.nih.gov

[The Latest Research Progress of Selinexor in the Treatment of Non-Hodgkin Lymphoma --Review]. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

The Association between Patient Characteristics and the Efficacy and Safety of Selinexor in Diffuse Large B-Cell Lymphoma in the SADAL Study. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Selinexor (KTP-330) - a selective inhibitor of nuclear export (SINE): anti-tumor activity in diffuse large B-cell lymphoma (DLBCL). [2020]