Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Polycythemia Vera

Polycythemia

Hematologic Diseases

Bone Marrow Neoplasms

Hematologic Neoplasms

Bone Marrow Diseases

Myeloproliferative Disorders

Chronic Myeloproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Antisickling Agents

Fibrinolytic Agents

Platelet Aggregation Inhibitors

Lenalidomide

Pomalidomide

Hydroxyurea

Janus Kinase Inhibitors

Anagrelide

Pipobroman

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Starting dose of 10 mg BID with individualized dose titration ranging from 5 mg once a day (QD) to 25 mg BID based on safety and efficacy

Best Available Therapy (BAT) will be selected by the Investigator for each participant. BAT may not include experimental agents (i.e. those not approved for the treatment of any indication) as well as a limited number of other selected drugs in accordance with the protocol-defined requirements.

Starting dose of 10 mg BID with individualized dose titration ranging from 5 mg QD to 25 mg BID based on safety and efficacy

ruxolitinib tablets

Best Available Therapy (BAT)

Srdan Verstovsek, MD,PhD

Mark Jones, MD

This pivotal phase III trial (CINC424B2301) is designed to compare the efficacy and safety of ruxolitinib (INC424) to Best Available Therapy (BAT) in participants with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea (HU).

Study of Efficacy and Safety in Polycythemia Vera Subjects Who Are Resistant to or Intolerant of Hydroxyurea: JAK Inhibitor INC424 (INCB018424) Tablets Versus Best Available Care: (The RESPONSE Trial)

Randomized, Open Label, Multicenter Phase III Study of Efficacy and Safety in Polycythemia Vera Subjects Who Are Resistant to or Intolerant of Hydroxyurea: JAK Inhibitor INC424 Tablets Versus Best Available Care (The RESPONSE Trial)

Primary response was defined as having achieved hematocrit control (the absence of phlebotomy eligibility beginning at the Week 8 visit and continuing through Week 32) and Spleen Volume Reduction (a greater than or equal to 35% reduction from baseline in spleen volume at Week 32).

Durable Primary Response was defined as any participant who achieved the primary outcome measure and who maintained their response up to 48 weeks after randomization.

Complete Hematological Remission at Week 32 was defined as any participant who achieved hematocrit control with a platelet count less than or equal to 400 X 10\^9/L and a white blood cell count less than or equal to 10 X 10\^9/L.

Durable Complete Hematological Remission was defined as any participant who achieved Complete Hematological Remission at Week 32 and maintained their response up to 48 weeks after randomization.

Durable Hematocrit Control was defined as any participant who achieved phlebotomy eligibility independence from Week 8 to Week 32 and maintained hematocrit control up to 48 weeks after randomization.

Durable Spleen Volume Reduction was defined as a participant who achieved at least 35% reduction from baseline in spleen volume at Week 32 and maintained that response 48 weeks after randomization.

Duration of the primary response is defined as the time from the first occurrence when both components of the primary endpoint are met until the date of the first documented disease progression (end of response).

Kaplan-Meier estimates are provided for duration of primary response.

Overall Clinicohematologic Response is defined as any participant who achieved a complete or partial clinicohematologic response per the European LeukemiaNet modified criteria for response in polycythemia vera (PV). A Complete Response (CR) is defined as: hematocrit control, spleen volume reduction at least 35% from baseline, platelet count less than or equal to 400 x 10(9)/L, and white blood cell count less than or equal to 10 x 10(9)/L. A Partial Response (PR) is defined as hematocrit control or response in all 3 of the other criteria.

Durable Complete or Partial Clinicohematologic Response was defined as any participant who achieved complete or partial clinicohematologic response per the European LeukemiaNet modified criteria for response in polycythemia vera at Week 32 and maintained that response 48 weeks after randomization.

Duration of the complete hematological remission is defined as the time from the first occurrence of complete hematological remission until the date of the first documented progression (end of response).

Kaplan-Meier estimates are provided for duration of complete hematological remission.

Duration of the absence of phlebotomy eligibility is defined as the time from the first occurrence of absence of phlebotomy eligibility until the date of the first documented progression.

Duration of spleen volume reduction is defined as the time from the first occurrence of a \>=35% reduction from baseline in spleen volume until the date of the first documented progression.

Duration of the overall clinicohematologic response was defined as the time from the first occurrence of complete response (CR) or partial response (PR) until the date of the first documented disease progression.

Novartis Pharmaceuticals

Incyte Corporation

Safety population: All participants who were enrolled and took at least 1 dose of study medication.

The initial data reported at Week 32 was based on MedDRA 15.1; the remaining data reported for end of study was based on MedDRA 20.1.

Ruxolitinib - Through Week 32

Best Available Therapy - Through Week 32

Ruxolitinib - Week 256 Close Out

Ruxolitinib

Best Available Therapy

Total

Age, Continuous

< 60 years

≥ 60 years

Age, Customized

Sex: Female, Male

White/Caucasian

Black/African American

Asian

Race/Ethnicity, Customized

Weight

Height was missing at study entry for one participant in the ruxolitinib arm.

Height

Body Mass Index (BMI)

Eastern Cooperative Oncology Group (ECOG) - ECOG Status: 0=Fully active, able to carry on all pre-disease performance without restriction; 1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; 2=Ambulatory and capable of all selfcare but unable to carry out any work activities up and about more than 50% of waking hours

ECOG performance status

All enrolled participants, regardless treated or not.

Study Director

Full Analysis Set (FAS) comprises all participants to whom study treatment had been assigned by randomization.

The Percentage of Participants Achieving a Primary Response at Week 32

The Percentage of Participants Achieving a Durable Primary Response at Week 48

The Percentage of Participants Achieving Complete Hematological Remission at Week 32

The Percentage of Participants Who Achieved a Durable Complete Hematological Remission at Week 48

The Percentage of Participants Who Achieved a Durable Hematocrit Control at Week 48

The Percentage of Participants Who Achieved Durable Spleen Volume Reduction at Week 48

16 weeks

32 weeks

48 weeks

64 weeks

80 weeks

96 weeks

112 weeks

128 weeks

144 weeks

160 weeks

176 weeks

192 weeks

208 weeks

224 weeks

240 weeks

256 weeks

Full Analysis Set (FAS) comprises all participants to whom study treatment had been assigned by randomization. Duration of response was pre-specified in the protocol to be analyzed for the ruxolitinib arm only considering the study design which allowed crossover for the BAT arm beginning at Week 32.

Estimated Duration of the Primary Response

Complete response rate

Partial response rate

The Percentage of Participants Who Achieved Overall Clinicohematologic Response at Week 32

The Percentage of Participants Achieving a Durable Complete or Partial Clinicohematologic Response at Week 48

Estimated Duration of the Complete Hematological Remission

Full Analysis Set (FAS) comprises all participants to whom study treatment had been assigned by randomization. Duration of the absence of phlebotomy eligibility was pre-specified in the protocol to be analyzed for the ruxolitinib arm only considering the study design which allowed crossover for the BAT arm beginning at Week 32.

Duration of the Absence of Phlebotomy Eligibility

Full Analysis Set (FAS) comprises all participants to whom study treatment had been assigned by randomization. Duration of the reduction in spleen volume was pre-specified in the protocol to be analyzed for the ruxolitinib arm only considering the study design which allowed crossover for the BAT arm beginning at Week 32.

Duration of Reduction in Spleen Volume

Full Analysis Set (FAS) comprises all participants to whom study treatment had been assigned by randomization. Duration of the overall clinicohematologic response was pre-specified in the protocol to be analyzed for the ruxolitinib arm only considering the study design which allowed crossover for the BAT arm beginning at Week 32.

Duration of The Overall Clinicohematologic Response

Starting dose of 10 mg twice a day (BID) with individualized dose titration ranging from 5 mg once a day (QD) to 25 mg BID based on safety and efficacy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of Efficacy and Safety in Polycythemia Vera Subjects Who Are Resistant to or Intolerant of Hydroxyurea: JAK Inhibitor INC424 (INCB018424) Tablets Versus Best Available Care: (The RESPONSE Trial)	NCT01243944	Polycythemia Ve...	ruxolitinib tab... Best Available ...	18 Years -	Incyte Corporation
Study of Efficacy and Safety in Polycythemia Vera Subjects Who Are Resistant to or Intolerant of Hydroxyurea: JAK Inhibitor INC424 (INCB018424) Tablets Versus Best Available Care: (The RESPONSE Trial)	NCT01243944	Polycythemia Ve...	ruxolitinib tab... Best Available ...	18 Years -	Incyte Corporation

Spots Global Cancer Trial Database for ruxolitinib tablets