A Study to Determine the Effect and Safety of an Oral Janus Kinase 2 (JAK2)-Inhibitor (Ruxolitinib; INBC018424) in Patients With Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this study was to determine clinical efficacy and safety of ruxolitinib (INCB018424), a small molecule Janus kinase 2 (JAK2)-inhibitor, in patients with refractory or relapsed multiple myeloma.

Detailed Description
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The protocol was originally designed as a Simon two stage but after it was determined that the initial 13 patients enrolled did not meet the definition of a 'responder' according to the International Uniform Response Criteria for multiple myeloma the protocol was amended to allow patients who had disease progression at any time or stable disease for 3 cycles and did not meet a withdrawal criterion or had withdrawn consent to have 40 mg of dexamethasone added to their dose of ruxolitinib.

Official Title
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A Phase 2, Two Stage, Open-label, Clinical Trial to Determine the Therapeutic Effect and Safety of an Oral JAK2-inhibitor (INCB018424) in Patients With Relapsed or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Ruxolitinib 25 mg
* Drug: Dexamethasone 40 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of multiple myeloma with evidence of measurable disease. Relapsed or refractory disease with at least one line of prior therapy. Adequate bone marrow reserve. Exclusion Criteria: Received anti-cancer medications or investigational therapy in the past 28 days. Intracranial disease or epidural disease.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ruxolitinib then Ruxolitinib + Dexamethasone<br>Patients received ruxolitinib 25 mg orally twice daily (bid) in each treatment cycle of 28 days. For those patients who had disease progression at any time or stable disease for 3 cycles and did not meet a withdrawal criterion, or withdrew consent, then 40 mg of dexamethasone was added to ruxolitinib on Days 1 to 4, 9 to 12, and 17 to 20 of four 28-day cycles. After the 4th cycle, 40 mg of dexamethasone was administered only on Days 1 to 4 of each subsequent cycle. Patients could continue to receive monotherapy or combination therapy indefinitely as long as no withdrawal criterion was met, did not have progressive disease and were receiving some clinical benefit. | Drug: Ruxolitinib 25 mg<br>* Ruxolitinib was supplied as 5 and 25 mg tablets.<br>* Other names: INCB018424;Drug: Dexamethasone 40 mg<br>* Dexamethasone was obtained commercially by Investigators in tablet strengths of 20 or 40 mg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Responders According to the International Uniform Response Criteria for Multiple Myeloma | A responder is defined as a patient with a complete response (negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow) or a partial response (≥ 50% reduction of serum M-protein and reduction in 24 h urinary M-protein by ≥ 90% or to < 200 mg per 24 h). | Day 1 of Cycles 2, 3, and 4 and then every 3 months thereafter (up to 25 months). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Disease Progression According to the International Uniform Response Criteria for Multiple Myeloma | Progressive Disease requires 1 or more of the following: Increase of ≥ 25% from baseline in: Serum M-component and/or (increase ≥ 0.5 g/dL). Urine M-component and/or (increase ≥ 200 mg/24 h). In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels increase must be > l0 mg/dL. Bone marrow plasma cell percentage ≥ 10%. Definite development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas. Development of hypercalcemia. | Day 1 of Cycles 2, 3, and 4 and then every 3 months thereafter (up to 25 months). |