Selinexor + Chemotherapy for Non-Hodgkin's Lymphoma

Recruiting at 1 trial location

Overseen By Clinical Trials Office-Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Barbara Ann Karmanos Cancer Institute

Must not be taking: Investigational agents

Disqualifiers: Brain metastases, HIV, Hepatitis B/C, others

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

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

Compensation: Varies

Number of Visits: 28

69 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase Ib/II trial is aimed at studying the combination of a drug named Selinexor (selective inhibitor of nuclear export) in combination with standard therapy for B cell Non-Hodgkin's lymphoma called R-CHOP. The investigators will establish maximum tolerated dose of Selinexor in combination with RCHOP and also study the efficacy of this combination for therapy of B cell Non-Hodgkin's lymphoma. Giving Selinexor plus chemotherapy may work better in treating patients with B cell non-Hodgkin lymphoma.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you have had prior chemotherapy or immunotherapy, you must wait at least 2 weeks before starting the trial treatment.

What data supports the effectiveness of the drug Selinexor for treating non-Hodgkin's lymphoma?

Research shows that Selinexor, a drug that blocks a protein involved in cancer cell growth, has shown promising results in treating non-Hodgkin's lymphoma. In a study, 31% of patients with this type of cancer had positive responses, including some complete and partial recoveries, indicating its potential effectiveness. ^{1 2 3 4 5}

Is the combination of Selinexor and chemotherapy safe for treating Non-Hodgkin's Lymphoma?

Selinexor has been studied in patients with Non-Hodgkin's Lymphoma and other cancers, showing some common side effects like low blood cell counts, fatigue, and low sodium levels. However, it is generally considered safe at the recommended dose, with serious organ-related side effects being rare. ^{1 2 4 6 7}

What makes the drug Selinexor unique for treating Non-Hodgkin's Lymphoma?

Selinexor is unique because it works by inhibiting the export of tumor suppressor proteins from the nucleus of cancer cells, which can lead to cancer cell death. This mechanism is different from traditional chemotherapy drugs that typically target cell division. ^{8 9 10 11 12}

Research Team

Dipenkumar Modi, M.D.

Principal Investigator

Barbara Ann Karmanos Cancer Institute

Eligibility Criteria

This trial is for adults with advanced B-cell non-Hodgkin lymphoma, including newly diagnosed and first relapse patients. It's suitable for those who haven't had anthracycline chemotherapy before or have only used non-anthracycline therapy once. Participants must be in good physical condition (ECOG <=1), not pregnant, willing to use contraception, and have a life expectancy over 6 months.

Inclusion Criteria

I am mostly self-sufficient and can carry out daily activities.

I have newly diagnosed DLBCL or low grade B cell NHL, or it's my first relapse after non-anthracycline chemo.

I have a low-grade B cell lymphoma such as follicular, marginal zone, indolent mantle cell lymphoma, or Waldenstrom's macroglobulinemia.

Exclusion Criteria

Pregnant and lactating women are excluded

Your liver enzymes (ALT and AST) are more than 2.5 times the normal level.

If you have HIV, active hepatitis B, or active hepatitis C, you cannot participate.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1B Treatment

Dose escalation of Selinexor in combination with RCHOP chemotherapy to establish the recommended phase 2 dose

Up to 21 days per cycle, 6 cycles

Weekly visits for toxicity monitoring

Phase 2 Treatment

Treatment with recommended phase 2 dose of Selinexor plus RCHOP for newly diagnosed DLBCL patients

Up to 21 days per cycle, 6 cycles

Maintenance

Patients achieving partial response or better receive maintenance Selinexor for up to 1 year

1 year

Visits every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Treatment Details

Interventions

• Selinexor

Trial Overview The trial tests Selinexor combined with R-CHOP chemotherapy to find the safest dose and see if it's more effective against B-cell non-Hodgkin lymphoma than standard treatments. The study includes two phases: Phase Ib determines the maximum tolerated dose of Selinexor; Phase II assesses its effectiveness.

Participant Groups

Group I: Treatment (selinexor, RCHOP) Experimental Treatment 1 Intervention

Patients will receive selinexor PO on days 1, 8, and 15 of a 21 week cycle. RCHOP will be given at standard dosing every 21 days. In the phase 1 part there is dose escalation for Selinexor in a 3+3 design. Treatment will be given for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with partial response or better will receive maintenance selinexor PO on days 1, 8, 15, and 22 every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

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?

Barbara Ann Karmanos Cancer Institute

Lead Sponsor

Trials

166

Recruited

9,300+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

The combination of the nuclear export inhibitor selinexor with dexamethasone (DEX) or everolimus (EVER) showed enhanced effectiveness against Non-Hodgkin Lymphoma (NHL) in both cell lines and animal models, indicating a promising therapeutic strategy.

Molecular analysis revealed that this combination therapy activates apoptotic signaling and down-regulates the nuclear exporter protein XPO1, supporting the mechanism of action for these drugs and providing a rationale for further clinical testing in Phase II trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-tumor activity of selective inhibitor of nuclear export (SINE) compounds, is enhanced in non-Hodgkin lymphoma through combination with mTOR inhibitor and dexamethasone. Muqbil, I., Aboukameel, A., Elloul, S., et al.[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]

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, an oral inhibitor of exportin 1 (XPO1), was found to be safe for patients with advanced solid tumors, with the most common side effects being mild to moderate fatigue, nausea, and anorexia, while serious toxicities were rare.

In a study of 189 patients, selinexor demonstrated some antitumor activity, with 4% of patients achieving a complete or partial response and 17% maintaining stable disease for at least 4 months, indicating its potential as a therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Class, First-in-Human Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Patients With Advanced Solid Tumors. Abdul Razak, AR., Mau-Soerensen, M., Gabrail, NY., et al.[2022]

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 systematic review of 11 studies involving 607 non-small cell lung cancer (NSCLC) patients, TAXs-based doublets showed a significantly higher overall response rate of 37.8% compared to 22% for PEM-based combinations, indicating that TAXs may be more effective as second-line therapy after platinum-based chemotherapy failure.

The median progression-free survival (PFS) was also better for TAXs at 5.3 months compared to 3.9 months for PEM, suggesting that TAXs-based treatments may provide a more favorable outcome for patients relapsing after initial treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platinum rechallenge in patients with advanced NSCLC: a pooled analysis. Petrelli, F., Coinu, A., Cabiddu, M., et al.[2022]

S-1, an oral anticancer drug, combined with irinotecan (CPT-11), showed effectiveness similar to the traditional FOLFIRI regimen in treating advanced colorectal cancer, as demonstrated in a case study of a 65-year-old man with lymph node metastasis.

The patient achieved a complete response after 5 courses of S-1 plus CPT-11, with no signs of relapse observed 18 months later, indicating the potential long-term efficacy of this treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment with S-1 plus CPT-11 for lymph node metastasis from colon cancer: report of a case. Yoshimatsu, K., Yokomizo, H., Fujimoto, T., et al.[2018]

In a trial involving 20 Japanese patients with metastatic renal cell carcinoma (RCC) who had previously failed cytokine therapy, S-1 demonstrated an objective response rate of 15%, with a median overall survival of 25.7 months.

S-1 was generally well tolerated, with the most common severe side effects being neutropenia and anorexia, both occurring in 20% of patients, indicating that while effective, monitoring for these adverse effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An early phase II trial of S-1 in Japanese patients with cytokine-refractory metastatic renal cell carcinoma. Naito, S., Tsukamoto, T., Usami, M., et al.[2013]

Docetaxel, a semisynthetic taxane, effectively stabilizes microtubules to induce cell-cycle arrest and apoptosis, showing improved survival rates in various cancers, including metastatic breast cancer and non-small-cell lung cancer.

Randomized trials have demonstrated that adding docetaxel to standard treatments enhances survival outcomes in high-risk early breast cancer and metastatic prostate cancer, highlighting its efficacy across multiple solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel for treatment of solid tumours: a systematic review of clinical data. Montero, A., Fossella, F., Hortobagyi, G., et al.[2022]

Docetaxel is an effective treatment for non-small cell lung cancer (NSCLC), showing comparable efficacy to newer platinum-based therapies in advanced stages, and has been approved for use in this context.

Clinical trials are ongoing to explore the best ways to combine docetaxel with other treatments, such as thoracic radiotherapy and molecularly targeted agents, to enhance its effectiveness in various stages of NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in non-small cell lung cancer: a review. Davies, AM., Lara, PN., Mack, PC., et al.[2019]

References

1. 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]

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

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

3. Ireland pubmed.ncbi.nlm.nih.gov

Anti-tumor activity of selective inhibitor of nuclear export (SINE) compounds, is enhanced in non-Hodgkin lymphoma through combination with mTOR inhibitor and dexamethasone. [2023]

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

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

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

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

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

First-in-Class, First-in-Human Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Patients With Advanced Solid Tumors. [2022]

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

Selinexor: First Global Approval. [2023]

8. Ireland pubmed.ncbi.nlm.nih.gov

Platinum rechallenge in patients with advanced NSCLC: a pooled analysis. [2022]

9. Greece pubmed.ncbi.nlm.nih.gov

Successful treatment with S-1 plus CPT-11 for lymph node metastasis from colon cancer: report of a case. [2018]

10. Germany pubmed.ncbi.nlm.nih.gov

An early phase II trial of S-1 in Japanese patients with cytokine-refractory metastatic renal cell carcinoma. [2013]

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

Docetaxel for treatment of solid tumours: a systematic review of clinical data. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Docetaxel in non-small cell lung cancer: a review. [2019]