A Trial of Selinexor, Ruxolitinib and Methylprednisolone

ConditionsMultiple Myeloma in Relapse Multiple Myeloma, Refractory

Trial statusRecruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexAll

AgeNot listed

SponsorOncotherapeutics

About this trial

Selinexor, a first-in-class, oral selective exportin 1 (XPO1) inhibitor, has shown promise in pre-clinical and clinical studies. It functions by inhibiting the nuclear export protein XPO1, resulting in the accumulation of tumor suppressor proteins and inhibition of oncoprotein mRNAs, which is selectively lethal to myeloma cells. Selinexor has demonstrated activity in combination with various drugs, including glucocorticoids and proteasome inhibitors, leading to its FDA approval for the treatment of relapsed or refractory multiple myeloma.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically

Hypercalcemia: serum calcium >0.25 mmol/L (>1mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11mg/dL)

Renal insufficiency: creatinine clearance <40 mL per minute or serum creatinine >177mol/L (>2mg/dL)

Anemia: hemoglobin value of >20g/L below the lowest limit of normal, or a hemoglobin value <100g/L

Disqualifiers

Patients who had prior exposure to ruxolitinib or selinexor

Prior malignancy that required treatment or has shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ) during the 3 years prior to randomization. Cancer treated with curative intent for >5 years previously and without evidence of recurrence will be allowed.

Have light chain amyloidosis

Have plasma cell leukemia

Trial design

Design model

Single group

Treatments tested in this trial

Selinexor
Drug
Selinexor (KPT-330) is a first-in-class, oral selective exportin 1 (XPO1) inhibitor (1,2). Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in t
Ruxolitinib
Drug
elective inhibitor of Janus kinase (JAK)
Methylprednisolone
Drug
Glucocorticoid, steroid

Treatment groups

30 Participants

are divided into 1 treatment group

Group A: Experimental: Selinexor/Ruxolitinib/SteroidsOther 3 interventions

Trial outcomes

Primary outcomes

1. Maximum Tolerated Dose (MTD):

● A standard 3 + 3 dose escalation schedule will be used for all escalations

Time frame

30 months

2. Recommended phase 2 dose (RP2D)

Primary objective of a phase 1 study is to define a safe and tolerable dose to use in further studies designed to determine efficacy, the Recommended Phase 2 Dose (RP2D)

Time frame

30 months

Secondary outcomes

1. Overall Response Rate ([ORR]=CR+VGPR+PR)

ORR is a measure of how many patients in a study experience a significant reduction or complete disappearance of their cancer following treatment, essentially indicating the percentage of patients who have a partial or complete response to the therapy being tested. ORR is calculated by adding the number of patients with a "Complete Response" + Very Good Partial Response + Partial Response.

Time frame

30 months

2. Clinical Benefit Rate ([CBR]=CR+VGPR+PR+MR)

The percentage of patients with advanced cancer who experience a complete or partial response to a treatment. CBR is calculated by adding the number of patients with Complete Response (CR) + Very Good Partial Response (VGPR) + Partial Response (PR) + Minor Response.

Time frame

30 months

3. To determine disease parameters for study treatment:

* Time to progression (TTP) - define as the time from the initiation of therapy to progressive disease * Progression-free survival (PFS) - defined as the time from initiation of therapy to progressive disease or death from any cause, whichever occurs first * Time to first response - defined as the time from the initiation of therapy to the first evidence of confirmed clinical benefit defined as \> minimal response (MR, including patients who achieved a complete response (CR), very good partial response (VGPR), partial response (PR), or MR * DOR - defined as the time from the first response to progressive disease * Overall survival (OS) - Overall survival, defined as the time from initiation of therapy to death from any cause or last follow-up visit

Time frame

30 months

Other outcomes

Background and rationale for assessment of serum B cell maturation antigen levels (sBCMA)

Only for MM patients participating in the optional biomarker including sBCMA analysis study. To evaluate the ability of MM-related biomarkers including sBCMA, to serve as: * Diagnostic biomarker by determining specificity and sensitivity in MM patients * Prognostic biomarker by determining its ability to predict the probable course of the disease including its recurrence. * Stratification biomarker by examining its ability to predict clinical outcomes of MM patients

Time frame

30 months

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Oncotherapeutics

Lead sponsor

Source ClinicalTrials.gov

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