Trial Outcomes & Findings for A Study to Determine the Effect and Safety of an Oral Janus Kinase 2 (JAK2)-Inhibitor (Ruxolitinib; INBC018424) in Patients With Multiple Myeloma (NCT NCT00639002)

Last Updated: 2018-02-13

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

13 participants

Primary outcome timeframe

Day 1 of Cycles 2, 3, and 4 and then every 3 months thereafter (up to 25 months).

Results posted on

2018-02-13

Participant Flow

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	13
Overall Study Received Ruxolitinib	13
Overall Study Received Ruxolitinib + Dexamethasone	7
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	13

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Death	1
Overall Study Adverse Event	1
Overall Study Protocol Violation	1
Overall Study Disease progression	3
Overall Study Physician Decision	6
Overall Study Lack of Efficacy	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ruxolitinib Then Ruxolitinib + Dexamethasone n=13 Participants 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.
Age, Continuous	74.7 years STANDARD_DEVIATION 8.36 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Stage of multiple myeloma at initial diagnosis I	0 participants n=5 Participants
Stage of multiple myeloma at initial diagnosis II	4 participants n=5 Participants
Stage of multiple myeloma at initial diagnosis III	4 participants n=5 Participants
Stage of multiple myeloma at initial diagnosis Unknown	5 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Ruxolitinib Then Ruxolitinib + Dexamethasone n=13 Participants 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.
Number of Responders According to the International Uniform Response Criteria for Multiple Myeloma	0 participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

Adverse Events

Ruxolitinib

Serious events: 6 serious events

Other events: 11 other events

Deaths: 0 deaths

Ruxolitinib + Dexamethasone

Serious events: 6 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Incyte Corporation

Phone: 855 463-3463

Results disclosure agreements

Principal investigator is a sponsor employee Following the first publication, the Institution and/or Principal Investigator may publish data or results from the Study, provided, however, that the Institution and/or Principal Investigator submits the proposed publication to the Sponsor for review at least sixty (60) days prior to the date of the proposed publication. Sponsor may remove from the proposed publication any information that is considered confidential and/or proprietary other than Study data and results.
Publication restrictions are in place

Restriction type: OTHER

Measure	Ruxolitinib n=13 participants at risk Patients received ruxolitinib 25 mg orally twice daily (bid) in each treatment cycle of 28 days until the following criteria were met: Disease progression at any time or stable disease for 3 cycles and did not meet a withdrawal criterion, or withdrew consent.	Ruxolitinib + Dexamethasone n=7 participants at risk Following administration of ruxolitinib 25 mg bid alone, for those patients who had disease progression at any time, stable disease for 3 cycles, 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.
Blood and lymphatic system disorders Anaemia	7.7% 1/13 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.	0.00% 0/7 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.
Cardiac disorders Cardiac failure congestive	7.7% 1/13 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.	0.00% 0/7 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.
Cardiac disorders Pericardial effusion	0.00% 0/13 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.	14.3% 1/7 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/13 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.	28.6% 2/7 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.
General disorders Disease progression	7.7% 1/13 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.	14.3% 1/7 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.
General disorders Pyrexia	7.7% 1/13 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.	0.00% 0/7 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.
General disorders Fatigue	0.00% 0/13 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.	14.3% 1/7 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.
General disorders Pain	0.00% 0/13 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.	14.3% 1/7 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.
Infections and infestations Pneumonia	7.7% 1/13 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.	28.6% 2/7 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.
Infections and infestations Urinary tract infection	7.7% 1/13 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.	0.00% 0/7 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.
Infections and infestations Pneumococcal sepsis	0.00% 0/13 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.	14.3% 1/7 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.
Injury, poisoning and procedural complications Overdose	0.00% 0/13 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.	14.3% 1/7 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/13 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.	14.3% 1/7 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung carcinoma cell type unspecified stage IV	0.00% 0/13 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.	14.3% 1/7 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.
Nervous system disorders Convulsion	0.00% 0/13 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.	14.3% 1/7 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	7.7% 1/13 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.	0.00% 0/7 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.
Vascular disorders Haematoma	7.7% 1/13 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.	0.00% 0/7 • Baseline to end of study Safety population: All subjects who were enrolled and took at least 1 dose of study medication.