69 Participants Needed

Selinexor + Chemotherapy for Non-Hodgkin's Lymphoma

Recruiting at 1 trial location
CT
Overseen ByClinical Trials Office-Call Center
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: Barbara Ann Karmanos Cancer Institute
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 2 JurisdictionsThis treatment is already approved in other countries

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.12345

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.12467

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.89101112

Research Team

Dipenkumar Modi, M.D. | Karmanos ...

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.
See 11 more

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.
See 12 more

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 OverviewThe 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
1Treatment groups
Experimental Treatment
Group I: Treatment (selinexor, RCHOP)Experimental Treatment1 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

Find a Clinic Near You

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.
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.
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.
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]

References

Pharmacodynamic and genomic markers associated with response to the XPO1/CRM1 inhibitor selinexor (KPT-330): A report from the pediatric preclinical testing program. [2023]
Selinexor therapy for multiple myeloma and non-Hodgkin lymphomas. [2023]
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]
Selective inhibition of nuclear export with selinexor in patients with non-Hodgkin lymphoma. [2021]
Phase 2 study of the Exportin 1 inhibitor selinexor in patients with recurrent gynecological malignancies. [2023]
First-in-Class, First-in-Human Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Patients With Advanced Solid Tumors. [2022]
Selinexor: First Global Approval. [2023]
Platinum rechallenge in patients with advanced NSCLC: a pooled analysis. [2022]
Successful treatment with S-1 plus CPT-11 for lymph node metastasis from colon cancer: report of a case. [2018]
An early phase II trial of S-1 in Japanese patients with cytokine-refractory metastatic renal cell carcinoma. [2013]
Docetaxel for treatment of solid tumours: a systematic review of clinical data. [2022]
Docetaxel in non-small cell lung cancer: a review. [2019]