Low-Dose Selinexor and Choline Salicylate for the Treatment of Patients With Non-Hodgkin Lymphoma or Histiocytic/Dendritic Cell Neoplasms

Overview

About this study

The purpose of this study is to learn about the combination of choline salicylate and selinexor. We want to find out more about the side effects of the combination, what doses are safe for patients, and to collect information on how lymphoma responds to the drug combination. The doses of both drugs received will depend on when  the patient is enrolled on to the study.

The drug combination of selinexor and choline salicylate is experimental and isn’t approved by the U.S. Food and Drug Administration (FDA). Selinexor is FDA approved when given with dexamethasone for previously treated relapsed multiple myeloma. Selinexor is currently being studied in DLBCL and other types of cancer. Choline salicylate has been used as a mild pain reliever, but has not been used in the treatment of cancer. The combination is investigational because the two drugs have never been given together. However, the FDA has allowed the use of this drug combination in this research study.

 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria - Registration:

  • Age ≥ 18 years.
  • Non-Hodgkin lymphoma or histiocytic/dendritic cell neoplasm meeting one of the following criteria: 
    • Biopsy-proven relapsed and/or refractory Non-Hodgkin lymphoma . Relapsed is defined as a relapse that occurred after having a response to the last therapy that lasted > 26 weeks. Refractory is no response (stable disease or progressive disease while on therapy) or relapse within 6 months. Refractoriness to autologous stem cell transplant will be defined as disease progression within 52 weeks following transplant.
    • Most recent tumor biopsy must be < 26 weeks prior to registration
    • Biopsy proven newly diagnosed histiocytic/dendritic cell neoplasm
    • Most recent tumor biopsy must be < 26 weeks prior to registration;
    • Biopsy-proven newly diagnosed histiocytic/dendritic cell neoplasms.
  • Measurable or assessable disease: Measurable disease is defined as measurable by CT (dedicated CT or the CT portion of a PET/CT) or MRI: To be considered measurable, there must be at least one lesion that has a single diameter of ≥1.5 cm.
    • NOTE: Skin lesions can be used if the area is ≥ 1.5cm in at least one diameter and photographed with a ruler. Patients with assessable disease by PET/CT are also eligible as long as the assessable disease is biopsy proven lymphoma or histiocytic/dendritic cell neoplasms.
  • Patients with non-Hodgkin lymphoma must have previously been treated with at least 2 lines of therapy. This requirement does not apply to patients with histiocytic histiocytic/dendritic cell neoplasms.
  • ECOG Performance Status (PS) of 0, 1, or 2.
  • The following laboratory values obtained ≤ 21 days prior to registration:
    • Absolute neutrophil count (ANC) ≥ 1,000/mm^3;
    • Platelet count ≥ 100,000/mm^3;
    • Hemoglobin ≥ 8.5 g/dL (may be transfused to reach criteria);
    • Total bilirubin < 2 x upper limit of normal (ULN) (or total bilirubin ≤ 3.0 x ULN with direct bilirubin ≤ 1.5 x ULN in patients with well-documented Gilbert’s Syndrome);
    • Aspartate transaminase (AST) ≤ 2.5 x ULN and alanine aminotransferase (ALT) ≤ 2.5 x ULN;
    • Calculated creatinine clearance must be ≥ 35 ml/min using the Cockcroft-Gault formula below:
    • Cockcroft-Gault Equation:
    • Creatinine clearance for males = (140 - age)(weight in kg)
    • ( 72)(serum creatinine in mg/dL)
    • Creatinine clearance for females =  (140 - age)(weight in kg)(0.85) ( 72)(serum creatinine in mg/dL).
  • Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only.
  • Female of childbearing potential (FCBP*) must commit to take highly effective contraceptive precautions** without interruption during the study and continue for at least 12 weeks after the last dose of selinexor and CS. FCBP must refrain from breastfeeding and donating oocytes during the course of the study.
  • Males must use an effective barrier method of contraception without interruption during the study and continue for at least 12 weeks after the last dose of selinexor and CS. They must refrain from donating sperm during the study participation.
  • * FCBP defined as sexually mature women who have not undergone bilateral tubal ligation, bilateral oophorectomy, or hysterectomy; or who have not been postmenopausal (i.e., who have not menstruated at all) for at least 1 year.
  • ** Highly effective forms of birth control are methods that achieve a failure rate of less than 1% per year when used consistently and correctly. Highly effective forms of birth control include: hormonal contraceptives (oral, injectable, patch, and intrauterine devices), male partner sterilization, or total abstinence from heterosexual intercourse, when this is the preferred and usual lifestyle of the patient.
    • NOTE: The double-barrier method (e.g., synthetic condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), periodic abstinence (such as calendar, symptothermal, post-ovulation), withdrawal (coitus interruptus), lactational amenorrhea method, and spermicide-only are not acceptable as highly effective methods of contraception.
  • Provide written informed consent.
  • Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
  • Willingness to provide mandatory blood specimens per protocol for PKs and banking, and mandatory tissue samples for correlative research.
    • NOTE: If an institution is not able to provide the tissue, it does not cause the patient to be ineligible; however, the collection of these tissues is strongly recommended.

Registration - Exclusion Criteria

  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
    • Pregnant women;
    • Nursing women.
  • Life expectancy of < 6 months.
  • Active GI dysfunction interfering with the ability to swallow tablets, or any GI dysfunction that could interfere with absorption of study treatment.
  • Known intolerance to or contraindications for choline salicylate therapy. Patients with known allergy to ASA are not eligible.
  • Prior exposure to a SINE compound, including selinexor.
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
  • Active second malignancy requiring treatment that would interfere with the assessment of the response of the lymphoma to this protocol therapy. Patients with treated malignancies on hormonal therapy (for example breast or prostate cancer) are eligible.
  • History of myocardial infarction ≤ 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.
  • Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤ 2 weeks prior to registration.
    • NOTE: Exception: patients on any BTK inhibitor (ibrutinib, zanabrutinib, acalabrutinib, etc.), venetoclax, or corticosteroids (any dose) may continue therapy up until the new regimen has started at investigator discretion. After the start of protocol therapy, corticosteroids can be used at  investigator’s discretion and tapered to lowest possible dose..
  • Active graft vs. host disease (after allogeneic stem cell transplantation) at registration.
  • Major surgery (including bowel resection) ≤ 3 weeks prior to registration.
  • Must not be currently eligible or have declined high-dose therapy with autologous stem cell transplantation rescue or CAR-T cell therapy.
  • Primary mediastinal (thymic) large B-cell lymphoma (PMBL).
  • Known active central nervous system (CNS) lymphoma. Patients with previous CNS involvement can enroll if the CNS component is inactive.
  • Patients who are on active anticoagulant therapy with direct oral anticoagulants (DOACs), aspirin or warfarin are not eligible due to potential bleeding. 
    • EXCEPTIONS: Patients who are on aspirin (81 mg) for primary prevention of cardiovascular disease can enroll, but the ASA needs to be held while on this protocol therapy. 
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
  • Patients known to have active hepatitis B, or C infection, or known to be positive for HCV RNA or HBsAg (HBV surface antigen). Patients known to be HIV positive, except those with CD4+ T-cell (CD4+) counts ≥ 350 cells/uL and on an established ART for at least twelve weeks and have an HIV viral load less than 400 copies/mL prior to enrollment.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Eligibility last updated 4/20/22. Questions regarding updates should be directed to the study team contact.

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Jonas Paludo, M.D.

Closed-enrolling by invitation

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"Close"
Not open to everyone who meets the eligibility criteria, but only those invited to participate by the study team.

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available
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CLS-20508603

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