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

Purpose

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.

Condition	Intervention	Phase
Relapsed Multiple Myeloma Refractory Multiple Myeloma Multiple Myeloma	Drug: Ruxolitinib 25 mg Drug: Dexamethasone 40 mg	Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Multiple Myeloma

Drug Information available for: Dexamethasone Dexamethasone acetate Dexamethasone sodium phosphate Ruxolitinib Ruxolitinib phosphate

U.S. FDA Resources

Further study details as provided by Incyte Corporation:

Primary Outcome Measures:

Number of Responders According to the International Uniform Response Criteria for Multiple Myeloma [ Time Frame: Day 1 of Cycles 2, 3, and 4 and then every 3 months thereafter (up to 25 months). ] [ Designated as safety issue: No ]
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 Outcome Measures:

Time to Disease Progression According to the International Uniform Response Criteria for Multiple Myeloma [ Time Frame: Day 1 of Cycles 2, 3, and 4 and then every 3 months thereafter (up to 25 months). ] [ Designated as safety issue: No ]
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.

Enrollment:	13
Study Start Date:	March 2008
Study Completion Date:	July 2010
Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 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 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 Ruxolitinib was supplied as 5 and 25 mg tablets. Other Name: INCB018424 Drug: Dexamethasone 40 mg Dexamethasone was obtained commercially by Investigators in tablet strengths of 20 or 40 mg.

Arms

Assigned Interventions

Experimental: 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 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

Ruxolitinib was supplied as 5 and 25 mg tablets.

Other Name: INCB018424

Drug: Dexamethasone 40 mg

Dexamethasone was obtained commercially by Investigators in tablet strengths of 20 or 40 mg.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00639002

Locations

United States, California

Highland, California, United States, 92346
United States, Florida

Boynton Beach, Florida, United States, 33435
United States, New York

New York, New York, United States, 10011

Sponsors and Collaborators

Incyte Corporation

Investigators

Principal Investigator:

Sundar Jagannath, MD

St. Vincent's Comprehensive Cancer Center, New York, New York

More Information

No publications provided

Responsible Party:	Incyte Corporation
ClinicalTrials.gov Identifier:	NCT00639002 History of Changes
Other Study ID Numbers:	INCB 18424-255
Study First Received:	March 12, 2008
Results First Received:	December 16, 2011
Last Updated:	June 5, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate

Dexamethasone
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on June 18, 2013