NCT01243944 · CITED IN SOURCE DOCUMENTS

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)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2019-03-06

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).

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

The Percentage of Participants Achieving a Primary Response at Week 32

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outcome · POSTED

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

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outcome · POSTED

The Percentage of Participants Achieving Complete Hematological Remission at Week 32

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Estimated Duration of the Primary Response

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Estimated Duration of the Complete Hematological Remission

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outcome · POSTED

Duration of the Absence of Phlebotomy Eligibility

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outcome · POSTED

Duration of Reduction in Spleen Volume

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outcome · POSTED

Duration of The Overall Clinicohematologic Response

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Participants diagnosed with PV for at least 24 weeks prior to screening according to the 2008 World Health Organization criteria * Participants resistant to or intolerant of hydroxyurea * Participants with a phlebotomy requirement * Participants with splenomegaly (palpable or non-palpable) and a spleen volume, as measured by MRI (or CT in applicable participants ), of greater than or equal to 450 cubic centimeters * Participants with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 Exclusion Criteria: * Women who are pregnant or nursing * Participants with inadequate liver or renal function * Participants with significant bacterial, fungal, parasitic, or viral infection requiring treatment * Participants with an active malignancy within the past 5 years, excluding specific skin cancers * Participants with known active hepatitis or HIV positivity * Participants who have previously received treatment with a JAK inhibitor * Participants being treated with any investigational agent
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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
intervention Names
Drug: ruxolitinib tablets
label
ruxolitinib tablets
type
EXPERIMENTAL
description
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.
intervention Names
Other: Best Available Therapy (BAT)
label
Best Available Therapy
type
OTHER

interventions

arm Group Labels
ruxolitinib tablets
description
Starting dose of 10 mg BID with individualized dose titration ranging from 5 mg QD to 25 mg BID based on safety and efficacy
name
ruxolitinib tablets
type
DRUG
arm Group Labels
Best Available Therapy
description
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.
name
Best Available Therapy (BAT)
other Names
BAT could include:
Hydroxyurea
IFN/PEG-IFN
Pipobroman
Anagrelide
Lenalidomide
Pomalidomide
Observation only
type
OTHER

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 222
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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).
measure
The Percentage of Participants Achieving a Primary Response at Week 32
time Frame
32 Weeks

secondary Outcomes

description
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.
measure
The Percentage of Participants Achieving a Durable Primary Response at Week 48
time Frame
48 Weeks
description
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.
measure
The Percentage of Participants Achieving Complete Hematological Remission at Week 32
time Frame
32 Weeks
description
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.
measure
The Percentage of Participants Who Achieved a Durable Complete Hematological Remission at Week 48
time Frame
48 Weeks
description
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.
measure
The Percentage of Participants Who Achieved a Durable Hematocrit Control at Week 48
time Frame
48 Weeks
description
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.
measure
The Percentage of Participants Who Achieved Durable Spleen Volume Reduction at Week 48
time Frame
48 Weeks
description
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.
measure
Estimated Duration of the Primary Response
time Frame
Through study completion, analysis was conducted when all participants had completed the Week 80 visit or discontinued the study
description
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.
measure
The Percentage of Participants Who Achieved Overall Clinicohematologic Response at Week 32
time Frame
32 Weeks
description
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.
measure
The Percentage of Participants Achieving a Durable Complete or Partial Clinicohematologic Response at Week 48
time Frame
48 Weeks
description
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.
measure
Estimated Duration of the Complete Hematological Remission
time Frame
Through study completion, analysis was conducted when all participants had completed the Week 80 visit or discontinued the study
description
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.
measure
Duration of the Absence of Phlebotomy Eligibility
time Frame
256 Weeks
description
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.
measure
Duration of Reduction in Spleen Volume
time Frame
256 Weeks
description
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.
measure
Duration of The Overall Clinicohematologic Response
time Frame
256 Weeks

Full study description

brief Summary: 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).

Source references

references

citation
Harrison CN, Kiladjian JJ, Hamer-Maansson JE, Naim A, Palandri F, Passamonti F. Ruxolitinib treatment in patients with polycythemia vera reduces JAK2 variant allele frequency and improves symptom burden and hematocrit control. Ther Adv Hematol. 2026 Mar 24;17:20406207261425083. doi: 10.1177/20406207261425083. eCollection 2026.
pmid
41890273
type
DERIVED
citation
Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. doi: 10.1016/S2352-3026(19)30207-8. Epub 2020 Jan 23.
pmid
31982039
type
DERIVED
citation
Kiladjian JJ, Guglielmelli P, Griesshammer M, Saydam G, Masszi T, Durrant S, Passamonti F, Jones M, Zhen H, Li J, Gadbaw B, Perez Ronco J, Khan M, Verstovsek S. Efficacy and safety of ruxolitinib after and versus interferon use in the RESPONSE studies. Ann Hematol. 2018 Apr;97(4):617-627. doi: 10.1007/s00277-017-3225-1. Epub 2018 Feb 2.
pmid
29396713
type
DERIVED
citation
Verstovsek S, Harrison CN, Kiladjian JJ, Miller C, Naim AB, Paranagama DC, Habr D, Vannucchi AM. Markers of iron deficiency in patients with polycythemia vera receiving ruxolitinib or best available therapy. Leuk Res. 2017 May;56:52-59. doi: 10.1016/j.leukres.2017.01.032. Epub 2017 Jan 31.
pmid
28193568
type
DERIVED
citation
Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with polycythemia vera: 80-week follow-up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. doi: 10.3324/haematol.2016.143644. Epub 2016 Apr 21.
pmid
27102499
type
DERIVED
citation
Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. doi: 10.1056/NEJMoa1409002.
pmid
25629741
type
DERIVED