Multiple Myeloma
Conditions
Brief summary
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
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who had disease progression at any time or stable disease for 3 cycles and did not meet a withdrawal criterion or had withdrawn consent to have 40 mg of dexamethasone added to their dose of ruxolitinib.
Interventions
DRUGRuxolitinib 25 mg
Ruxolitinib was supplied as 5 and 25 mg tablets.
Dexamethasone was obtained commercially by Investigators in tablet strengths of 20 or 40 mg.
Sponsors
Incyte Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Responders According to the International Uniform Response Criteria for Multiple Myeloma | Day 1 of Cycles 2, 3, and 4 and then every 3 months thereafter (up to 25 months). | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Disease Progression According to the International Uniform Response Criteria for Multiple Myeloma | Day 1 of Cycles 2, 3, and 4 and then every 3 months thereafter (up to 25 months). | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ruxolitinib Then Ruxolitinib + Dexamethasone 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 for 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. | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 1 |
| Overall Study | Disease progression | 3 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Physician Decision | 6 |
| Overall Study | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | Ruxolitinib Then Ruxolitinib + Dexamethasone |
|---|---|
| Age, Continuous | 74.7 years STANDARD_DEVIATION 8.36 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 8 Participants |
| Stage of multiple myeloma at initial diagnosis I | 0 participants |
| Stage of multiple myeloma at initial diagnosis II | 4 participants |
| Stage of multiple myeloma at initial diagnosis III | 4 participants |
| Stage of multiple myeloma at initial diagnosis Unknown | 5 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 13 | 6 / 7 |
| serious Total, serious adverse events | 6 / 13 | 6 / 7 |
Outcome results
Primary
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).
Time frame: Day 1 of Cycles 2, 3, and 4 and then every 3 months thereafter (up to 25 months).
Population: Intent-to-treat population: All patients who were enrolled and took at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruxolitinib Then Ruxolitinib + Dexamethasone | Number of Responders According to the International Uniform Response Criteria for Multiple Myeloma | 0 participants |
Secondary
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.
Time frame: Day 1 of Cycles 2, 3, and 4 and then every 3 months thereafter (up to 25 months).
Population: Intent-to-treat population. This outcome measure was not analyzed as no patients achieved a response.