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.
PRIMARY OBJECTIVE: I. To evaluate the maximum tolerated dose (MTD) of choline salicylate (CS) that can be combined with selinexor twice weekly in patients with relapsed/refractory non-Hodgkin, Hodgkin lymphoma, histiocytic/dendritic cell neoplasms, or relapsed/refractory (RR) multiple myeloma (MM). SECONDARY OBJECTIVE: I. To evaluate the response \[overall response rate (ORR), clinical benefit rate (CBR) and duration of response (DOR)) of selinexor and CS in patients with relapsed/refractory non-Hodgkin or Hodgkin lymphoma, histiocytic/dendritic cell neoplasms, or multiple myeloma. CORRELATIVE RESEARCH OBJECTIVE: I. To determine if CRM1, RAD51, gH2AX, BRCA1 and 53BP1 expressions in malignant lymphoma cells, extramedullary myeloma, or histiocytic/dendritic cell neoplasm cells from those patients treated on this study have a predictive role. OUTLINE: This is a dose-escalation study. Patients receive selinexor orally (PO) twice a week (BIW) on days 1, 3, 8, 10, 15, 17, 22, and 24, and choline salicylate PO three times daily (TID) on days 1-28. Patients undergoing pharmacokinetic analysis receive choline salicylate beginning on day 3 of cycle 1 (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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
22
Given PO
Given PO
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Maximum tolerated dose of the combination of low-dose selinexor with choline salicylate
Defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients).
Time frame: Up to 12 cycles (a cycle is 28 days)
Incidence of adverse events
Adverse events will be assessed according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns (overall and by dose level). Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
Time frame: Up to 12 cycles
Overall response rate
Noted as the objective status at any time before progression or initiation of new treatment. Response will be evaluated using all cycles of treatment. Defined as the following for patients with Multiple Myeloma: stringent Complete Response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR), stable disease (SD), progressive disease (PD), and clinical relapse (REL). Defined as the following for patients with Non-Hodgkin or Hodgkin lymphoma or Histiocytic/dendritic cell neoplasms: complete metabolic response (CMR), partial metabolic response (PMR), or prolonged stable disease (SD) (duration of at least 3 months).
Time frame: Up to 12 cycles (a cycle is 28 days)
Clinical benefit rate
Noted as the objective status at any time before progression or initiation of new treatment. Response will be evaluated using all cycles of treatment. Defined as the following for patients with Multiple Myeloma: sCR, CR, VGPR, PR, MR, SD, PD, and REL. Defined as the following for patients with Non-Hodgkin or Hodgkin lymphoma or Histiocytic/dendritic cell neoplasms: CMR, PMR, or prolonged SD (duration of at least 3 months).
Time frame: Up to 12 cycles (a cycle is 28 days)
Duration of response
Defined for all evaluable patients who have achieved a response as the date at which the patient's objective status is first noted to the earliest date progression is documented.
Time frame: Up to 12 cycles (a cycle is 28 days)
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