A Study of Ruxolitinib vs Best Available Therapy (BAT) in Patients With Steroid-refractory Chronic Graft vs. Host Disease (GvHD) After Bone Marrow Transplantation (REACH3)
Sponsor
Incyte Corporation (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03112603
Collaborator
(none)
332
191
2
57.3
1.7
0
Study Details
Study Description
Brief Summary
The purpose of this study is to assess the efficacy of ruxolitinib against best available therapy in participants with steroid-refractory chronic graft-versus-host disease (SR cGvHD).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
332 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase III Randomized Open-label Multi-center Study of Ruxolitinib vs. Best Available Therapy in Patients With Corticosteroid-refractory Chronic Graft vs Host Disease After Allogeneic Stem Cell Transplantation (REACH3)
Actual Study Start Date
:
Mar 7, 2018
Actual Primary Completion Date
:
May 8, 2020
Anticipated Study Completion Date
:
Dec 14, 2022
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Ruxolitinib Ruxolitinib for the treatment period and extension period. |
Drug: Ruxolitinib
Ruxolitinib twice daily at the protocol-defined starting dose.
Other Names:
|
| Active Comparator: Best Available Therapy Best available therapy for the treatment period and extension period, with optional crossover to ruxolitinib after Cycle 6. |
Drug: Extracorporeal photopheresis (ECP)
Best available therapy (BAT) will be selected by the investigator for each participant. BAT may not include experimental agents (ie, 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. The BAT in this study will be among the following treatments currently used in this setting (no other types or combinations of BATs are permitted in this study).
Drug: Low-dose methotrexate (MTX)
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
Drug: Mycophenolate mofetil (MMF)
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
Drug: mechanistic Target of Rapamycin (mTOR) inhibitors (everolimus or sirolimus)
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
Drug: Infliximab
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
Drug: Rituximab
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
Drug: Pentostatin
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
Drug: Imatinib
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
Drug: Ibrutinib
Patients will receive BAT based on the Investigator's opinion, taking into account the manufacturer's instructions, labeling, subject's medical condition, and institutional guidelines for any dose adjustment.
|
Outcome Measures
Primary Outcome Measures
- Efficacy of Ruxolitinib Versus Investigator's Choice Best Available Therapy (BAT) in Participants With Moderate or Severe SR-cGvHD Assessed by Overall Response Rate (ORR) at the Cycle 7 Day 1 Visit [Cycle 7 Day 1]
ORR defined as the percentage of participants in each arm demonstrating a complete response (CR) or partial response (PR) based on Chronic GvHD Disease assessments (NIH Consensus Criteria, Lee 2015) without the requirement of additional systemic therapies for an earlier progression, mixed response or non-response. Scoring of response will be relative to the organ score at the time of randomization.
Secondary Outcome Measures
- Rate of Participants With Clinically Relevant Improvement of the Modified Lee cGvHD Symptom Scale Score [Cycle 7 Day 1]
To assess improvement of symptoms based on the total symptom score (TSS); a responder is defined as having achieved a clinically relevant reduction from baseline of the TSS. Scale that consists of 30 items in 7 subscales (skin, eye, mouth, lung, nutrition, energy and psychological). Patients report their level of symptom "bother" over the previous month on a 5-point likert scale: not at all, slightly, moderately, quite a bit, or extremely. Subscale scores and the summary score range from 0 to 100, with a higher score indicating worse symptoms.
- Rate of Failure-free Survival (FFS) [Baseline to last patient reached Cycle 7 Day 1]
Composite time to event endpoint incorporating the following FFS events: i) relapse or recurrence of underlying disease or death due to underlying disease, ii) nonrelapse mortality, or iii) addition or initiation of another systemic therapy for chronic GvHD (cGvHD).
- Best Overall Response (BOR) [up to Cycle 7 Day 1]
Defined as percentage of participants who achieved an overall response (CR+PR) based on based on Chronic GvHD Disease assessments (NIH Consensus Criteria, Lee 2015) at any time point (up to Cycle 7 Day 1 or the start of additional systemic therapy for cGvHD.
- ORR at End of Cycle 3 [Cycle 4 Day 1]
ORR defined as the percentage of participants in each arm demonstrating a complete response (CR) or partial response (PR) based on Chronic GvHD Disease assessments (NIH Consensus Criteria, Lee 2015) without the requirement of additional systemic therapies for an earlier progression, mixed response or non-response. Scoring of response will be relative to the organ score at the time of randomization.
- Duration of Response [First response to the last patient reached C7D1]
Assessed for responders only; response based on Chronic GvHD Disease assessments (NIH consensus criteria Lee 2015).
- Overall Survival (OS) [From the date of randomization to the date of death due to any cause up to approximately 36 months.]
Defined as the time from the date of randomization to the date of death due to any cause.
- Cumulative Incidence of Non-relapse Mortality (NRM) [Months 3, 6, 12, 18, and 24]
Defined as the cumulative incidence rate from competing risk analysis for NRM from date of randomization to date of death not preceded by underlying disease relapse/recurrence.
- Percentage of Participants With ≥ 50% Reduction in Daily Corticosteroid Dose at Cycle 7 Day 1 [Cycle 7 Day 1]
All corticosteroid dosages prescribed to the patient and all dose changes during the study will be recorded for assessment of participants with ≥ 50% reduction in daily corticosteroid dose.
- Percentage of Participants Successfully Tapered Off All Corticosteroids at Cycle 7 Day 1 [Cycle 7 Day 1]
All corticosteroid dosages prescribed to the patient and all dose changes during the study will be recorded for assessment of participants who successfully tapered off all corticosteroids.
- Cumulative Incidence of Malignancy Relapse/Recurrence (MR) [At 3, 6, 12, 18, and 24 months]
Defined as the cumulative incidence rate from competing risk analysis of MR from date of randomization to hematologic malignancy relapse/recurrence. Calculated for participants with underlying hematologic malignant disease.
- Changes in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) [Up to Cycle 24 Day 1]
The mean change from baseline of the FACT-BMT questionnaire. FACTBMT is a 50-item self-report questionnaire that measures the effect of a therapy on domains including physical, functional, social/family, and emotional well-being, together with additional concerns relevant for bone marrow transplantation patients. The questions were based on 5-point Likert scale, where 0 corresponds to 'not at all' and 4 correspond to 'very much'. The higher the final score, the better the quality of life. The FACT-BMT total score range from 0 to 148.
- Changes in EQ-5D-5L [Up to Cycle 24 Day 1]
The EQ-5D-5L: a descriptive classification consisting of five dimensions of health: mobility, self-care, usual activities, anxiety/depression, and pain/discomfort (Brooks 1996). The five-level version (no problems, slight problems, moderate problems, severe problems, and extreme problems) uses a 5-point likert scale with 1 being no problems and 5 being extreme problems.
- Incidence and Severity of Adverse Events [From baseline to 30-35 days after end of treatment, up to approximately 36 months]
Adverse events include occurrence of any second primary malignancies, infections, physical exam findings, changes in vital signs, routine serum chemistry, hematology results, and coagulation profile.
- Pharmacokinetics Parameter : Cmax of Ruxolitinib [Cycle 1 Day 1 and Day 15]
Maximum Observed Plasma Concentration of ruxolitinib
- Pharmacokinetics Parameter : AUC Last of Ruxolitinib [Cycle 1 Day 1 and Day 15]
Area Under the concentration- time curve up to the last measurable concentration of ruxolitinib
- Pharmacokinetics Parameter : AUCinf of Ruxolitinib [Cycle 1 Day 1 and Day 15]
Area Under the Concentration-time Curve From 0 to Infinity of ruxolitinib
- Pharmacokinetics Parameter : CL/F of Ruxolitinib [Cycle 1 Day 1 and Day 15]
Oral dose clearance of ruxolitinib
- Pharmacokinetics Parameter : Vz/F of Ruxolitinib [Cycle 1 Day 1 and Day 15]
Apparent oral dose volume of distribution of ruxolitinib
- Pharmacokinetics Parameter : Tmax of Ruxolitinib [Cycle 1 Day 1 and Day 15]
Time to reach maximum plasma concentration of ruxolitinib
- Pharmacokinetics Parameter : T1/2 of Ruxolitinib [Cycle 1 Day 1 and Day 15]
Apparent terminal phase disposition half-life of ruxolitinib
- Utilization of Medical Resources [Baseline to last patient reached Cycle 7 Day 1]
Percentage of subjects with at least one submission to healthcare encounter.
Eligibility Criteria
Criteria
Ages Eligible for Study:
12 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Have undergone allogeneic stem cell transplantation (alloSCT) from any donor source (matched unrelated donor, sibling, haplo-identical) using bone marrow, peripheral blood stem cells, or cord blood. Recipients of non-myeloablative, myeloablative, and reduced intensity conditioning are eligible
-
Evident myeloid and platelet engraftment: Absolute neutrophil count (ANC) > 1000/mm3 and platelet count > 25,000/ mm3
-
Participants with clinically diagnosed moderate to severe cGvHD according to NIH
Consensus Criteria prior to randomization:
-
Moderate cGvHD: At least one organ (not lung) with a score of 2, 3 or more organs involved with a score of 1 in each organ, or lung score of 1
-
Severe cGvHD: at least 1 organ with a score of 3, or lung score of 2 or 3
-
Participants currently receiving systemic or topical corticosteroids for the treatment of cGvHD for a duration of < 12 months prior to Cycle 1 Day 1 (if applicable), and have a confirmed diagnosis of steroid-refractory cGvHD defined per 2014 NIH consensus criteria irrespective of the concomitant use of a calcineurin inhibitor (CNI), as follows:
-
A lack of response or disease progression after administration of minimum prednisone 1 mg/kg/day for at least 1 week, OR
-
Disease persistence without improvement despite continued treatment with prednisone at > 0.5 mg/kg/day or 1 mg/kg/every other day for at least 4 weeks, OR
-
Increase to prednisolone dose to > 0.25 mg/kg/day after 2 unsuccessful attempts to taper the dose
-
Participant must accept to be treated with only one of the following BAT options on Cycle 1 Day 1 (additions and changes are allowed during the course of the study, but only with BAT from the following BAT options): extracorporeal photopheresis (ECP), low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab, pentostatin, imatinib, ibrutinib
Exclusion Criteria:
-
Participants who have received 2 or more systemic treatment for cGvHD in addition to corticosteroids ± CNI for cGvHD
-
Patients that transition from active aGvHD to cGvHD without tapering off corticosteroids ± CNI and any systemic treatment
- Patients receiving up to 30 mg by mouth once a day of hydrocortisone (i.e., physiologic replacement dose) of corticosteroids are allowed.
-
Participants who were treated with prior JAK inhibitors for aGvHD; except when the participant achieved complete or partial response and has been off JAK inhibitor treatment for at least 8 weeks prior to Cycle 1 Day 1
-
Failed prior alloSCT within the past 6 months from Cycle 1 Day 1
-
Participants with relapsed primary malignancy, or who have been treated for relapse after the alloSCT was performed
-
Steroid refractory cGvHD occurring after a non-scheduled donor lymphocyte infusion (DLI) administered for preemptive treatment of malignancy recurrence. Participants who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible
-
Any corticosteroid therapy for indications other than cGvHD at doses > 1 mg/kg/day methylprednisolone or equivalent within 7 days of Cycle 1 Day 1
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Incyte Investigative Site | Tucson | Arizona | United States | 85724 |
| 2 | Incyte Investigative Site | Duarte | California | United States | 31010 |
| 3 | Incyte Investigative Site | La Jolla | California | United States | 92093-0987 |
| 4 | Incyte Investigative Site | Los Angeles | California | United States | 90033 |
| 5 | Incyte Investigative Site | New Haven | Connecticut | United States | 06510 |
| 6 | Incyte Investigative Site | Wilmington | Delaware | United States | 19803 |
| 7 | Incyte Investigative Site | Gainesville | Florida | United States | 32610 |
| 8 | Incyte Investigative Site | Tampa | Florida | United States | 33612 |
| 9 | Incyte Investigative Site | Chicago | Illinois | United States | 60611 |
| 10 | Incyte Investigative Site | Chicago | Illinois | United States | 60612 |
| 11 | Incyte Investigative Site | Chicago | Illinois | United States | 60637 |
| 12 | Incyte Investigative Site | Maywood | Illinois | United States | 60153 |
| 13 | Incyte Investigative Site | Indianapolis | Indiana | United States | 46237 |
| 14 | Incyte Investigative Site | Westwood | Kansas | United States | 66205 |
| 15 | Incyte Investigative Site | Lexington | Kentucky | United States | 40536 |
| 16 | Incyte Investigative Site | Boston | Massachusetts | United States | 02114 |
| 17 | Incyte Investigative Site | Boston | Massachusetts | United States | 02215 |
| 18 | Incyte Investigative Site | Omaha | Nebraska | United States | 68198-7680 |
| 19 | Incyte Investigative Site | Hackensack | New Jersey | United States | 07601 |
| 20 | Incyte Investigative Site | New York | New York | United States | 10021 |
| 21 | Incyte Investigative Site | New York | New York | United States | 10032 |
| 22 | Incyte Investigative Site | New York | New York | United States | 11040 |
| 23 | Incyte Investigative Site | Chapel Hill | North Carolina | United States | 27599 |
| 24 | Incyte Investigative Site | Durham | North Carolina | United States | 27710 |
| 25 | Incyte Investigative Site | Winston-Salem | North Carolina | United States | 27157 |
| 26 | Incyte Investigative Site | Cincinnati | Ohio | United States | 45242 |
| 27 | Incyte Investigative Site | Cleveland | Ohio | United States | 44106-5048 |
| 28 | Incyte Investigative Site | Cleveland | Ohio | United States | 44195 |
| 29 | Incyte Investigative Site | Columbus | Ohio | United States | 43210 |
| 30 | Incyte Investigative Site | Oklahoma City | Oklahoma | United States | 73104 |
| 31 | Incyte Investigative Site | Philadelphia | Pennsylvania | United States | 19104 |
| 32 | Incyte Investigative Site | Pittsburgh | Pennsylvania | United States | 15224 |
| 33 | Incyte Investigative Site | Pittsburgh | Pennsylvania | United States | 15232 |
| 34 | Incyte Investigative Site | Nashville | Tennessee | United States | 37232 |
| 35 | Incyte Investigative Site | Dallas | Texas | United States | 75390 |
| 36 | Incyte Investigative Site | Houston | Texas | United States | 77030 |
| 37 | Incyte Investigative Site | Seattle | Washington | United States | 98109 |
| 38 | Incyte Investigative Site | Milwaukee | Wisconsin | United States | 53226 |
| 39 | Novartis Investigative Site | Darlinghurst | New South Wales | Australia | 2010 |
| 40 | Novartis Investigative Site | Parkville | Victoria | Australia | 3002 |
| 41 | Novartis Investigative Site | Innsbruck | Tyrol | Austria | 6020 |
| 42 | Novartis Investigative Site | Graz | Austria | 8036 | |
| 43 | Novartis Investigative Site | Linz | Austria | A-4010 | |
| 44 | Novartis Investigative Site | Vienna | Austria | A-1090 | |
| 45 | Novartis Investigative Site | Antwerpen | Belgium | 2060 | |
| 46 | Novartis Investigative Site | Brugge | Belgium | 8000 | |
| 47 | Novartis Investigative Site | Bruxelles | Belgium | 1200 | |
| 48 | Novartis Investigative Site | Gent | Belgium | 9000 | |
| 49 | Novartis Investigative Site | Leuven | Belgium | 3000 | |
| 50 | Novartis Investigative Site | Liege | Belgium | 4000 | |
| 51 | Novartis Investigative Site | Sofia | Bulgaria | 1527 | |
| 52 | Novartis Investigative Site | Sofia | Bulgaria | 1756 | |
| 53 | Novartis Investigative Site | Vancouver | British Columbia | Canada | V5Z 1M9 |
| 54 | Novartis Investigative Site | Hamilton | Ontario | Canada | L8V 5C2 |
| 55 | Novartis Investigative Site | Ottawa | Ontario | Canada | K1H 8L6 |
| 56 | Novartis Investigative Site | Toronto | Ontario | Canada | M5G 2M9 |
| 57 | Novartis Investigative Site | Praha 2 | Czech Republic | Czechia | 128 20 |
| 58 | Novartis Investigative Site | Hradec Kralove | CZE | Czechia | 500 05 |
| 59 | Novartis Investigative Site | Praha 5 | Czechia | 150 06 | |
| 60 | Novartis Investigative Site | Copenhagen | Denmark | DK-2100 | |
| 61 | Novartis Investigative Site | Odense | Denmark | DK 5000 | |
| 62 | Novartis Investigative Site | Bordeaux | Aquitaine | France | 33076 |
| 63 | Novartis Investigative Site | Amiens cedex1 | France | 80054 | |
| 64 | Novartis Investigative Site | Caen Cedex 9 | France | 14033 | |
| 65 | Novartis Investigative Site | Lille Cedex | France | 59037 | |
| 66 | Novartis Investigative Site | Limoges cedex | France | 87042 | |
| 67 | Novartis Investigative Site | Lyon Cedex 08 | France | 69373 | |
| 68 | Novartis Investigative Site | Montpellier cedex 5 | France | 34295 | |
| 69 | Novartis Investigative Site | Paris cedex 10 | France | 75475 | |
| 70 | Novartis Investigative Site | PARIS Cedex 12 | France | 75571 | |
| 71 | Novartis Investigative Site | Paris Cedex 19 | France | 75935 | |
| 72 | Novartis Investigative Site | Pierre-Benite Cédex | France | 69495 | |
| 73 | Novartis Investigative Site | Rennes Cedex 9 | France | 35033 | |
| 74 | Novartis Investigative Site | Rouen Cedex 1 | France | 76038 | |
| 75 | Novartis Investigative Site | Saint Priest en Jarez Cedex | France | 42271 | |
| 76 | Novartis Investigative Site | Strasbourg Cedex | France | 67098 | |
| 77 | Novartis Investigative Site | Toulouse Cedex 9 | France | 31059 | |
| 78 | Novartis Investigative Site | Vandoeuvre les Nancy cedex | France | 54511 | |
| 79 | Novartis Investigative Site | Mannheim | Baden-Württemberg | Germany | 68167 |
| 80 | Novartis Investigative Site | Augsburg | Germany | 86156 | |
| 81 | Novartis Investigative Site | Berlin | Germany | 13125 | |
| 82 | Novartis Investigative Site | Dresden | Germany | 01307 | |
| 83 | Novartis Investigative Site | Duesseldorf | Germany | 40225 | |
| 84 | Novartis Investigative Site | Erlangen | Germany | 91054 | |
| 85 | Novartis Investigative Site | Essen | Germany | 45147 | |
| 86 | Novartis Investigative Site | Frankfurt | Germany | 60590 | |
| 87 | Novartis Investigative Site | Freiburg | Germany | 79106 | |
| 88 | Novartis Investigative Site | Hamburg | Germany | 20099 | |
| 89 | Novartis Investigative Site | Hamburg | Germany | 20246 | |
| 90 | Novartis Investigative Site | Jena | Germany | 07747 | |
| 91 | Novartis Investigative Site | Kiel | Germany | 24105 | |
| 92 | Novartis Investigative Site | Koeln | Germany | 50937 | |
| 93 | Novartis Investigative Site | Leipzig | Germany | 04103 | |
| 94 | Novartis Investigative Site | Mainz | Germany | 55131 | |
| 95 | Novartis Investigative Site | Mannheim | Germany | 68167 | |
| 96 | Novartis Investigative Site | Muenster | Germany | 48149 | |
| 97 | Novartis Investigative Site | Ulm | Germany | ||
| 98 | Novartis Investigative Site | Würzburg | Germany | 97080 | |
| 99 | Novartis Investigative Site | Athens | GR | Greece | |
| 100 | Novartis Investigative Site | Patras | GR | Greece | 265 00 |
| 101 | Novartis Investigative Site | Thessaloníki | GR | Greece | |
| 102 | Novartis Investigative Site | Athens | Greece | ||
| 103 | Novartis Investigative Site | Budapest | Hungary | 1097 | |
| 104 | Novartis Investigative Site | Navi Mumbai | Maharashtra | India | 410210 |
| 105 | Novartis Investigative Site | Pune | Maharashtra | India | 411004 |
| 106 | Novartis Investigative Site | Delhi | India | 110 085 | |
| 107 | Novartis Investigative Site | Vellore | India | 632004 | |
| 108 | Novartis Investigative Site | Haifa | Israel | 31096 | |
| 109 | Novartis Investigative Site | Jerusalem | Israel | 91120 | |
| 110 | Novartis Investigative Site | Petach Tikva | Israel | 49100 | |
| 111 | Novartis Investigative Site | Tel Aviv | Israel | 64239 | |
| 112 | Novartis Investigative Site | Ancona | AN | Italy | 60126 |
| 113 | Novartis Investigative Site | Bergamo | BG | Italy | 24127 |
| 114 | Novartis Investigative Site | Bologna | BO | Italy | 40138 |
| 115 | Novartis Investigative Site | Brescia | BS | Italy | 25123 |
| 116 | Novartis Investigative Site | Genova | GE | Italy | 16132 |
| 117 | Novartis Investigative Site | Genova | GE | Italy | 16147 |
| 118 | Novartis Investigative Site | Milano | MI | Italy | 20132 |
| 119 | Novartis Investigative Site | Milano | MI | Italy | 20133 |
| 120 | Novartis Investigative Site | Rozzano | MI | Italy | 20089 |
| 121 | Novartis Investigative Site | Palermo | PA | Italy | 90146 |
| 122 | Novartis Investigative Site | Pescara | PE | Italy | 65124 |
| 123 | Novartis Investigative Site | Parma | PR | Italy | 43100 |
| 124 | Novartis Investigative Site | Pavia | PV | Italy | 27100 |
| 125 | Novartis Investigative Site | Roma | RM | Italy | 00133 |
| 126 | Novartis Investigative Site | Roma | RM | Italy | 00165 |
| 127 | Novartis Investigative Site | Roma | RM | Italy | 00168 |
| 128 | Novartis Investigative Site | Torino | TO | Italy | 10126 |
| 129 | Novartis Investigative Site | Udine | UD | Italy | 33100 |
| 130 | Novartis Investigative Site | Perugia | Italy | 06132 | |
| 131 | Novartis Investigative Site | Nagoya-city | Aichi | Japan | 453-8511 |
| 132 | Novartis Investigative Site | Fukuoka-city | Fukuoka | Japan | 812-8582 |
| 133 | Novartis Investigative Site | Sapporo-city | Hokkaido | Japan | 060-8648 |
| 134 | Novartis Investigative Site | Kobe-city | Hyogo | Japan | 650-0047 |
| 135 | Novartis Investigative Site | Nishinomiya-city | Hyogo | Japan | 663 8501 |
| 136 | Novartis Investigative Site | Isehara-city | Kanagawa | Japan | 259-1193 |
| 137 | Novartis Investigative Site | Sendai-city | Miyagi | Japan | 980-8574 |
| 138 | Novartis Investigative Site | Osaka-city | Osaka | Japan | 545-8586 |
| 139 | Novartis Investigative Site | Suita-city | Osaka | Japan | 565-0871 |
| 140 | Novartis Investigative Site | Shimotsuke-city | Tochigi | Japan | 329-0498 |
| 141 | Novartis Investigative Site | Bunkyō-ku | Tokyo | Japan | 113-8677 |
| 142 | Novartis Investigative Site | Minato-ku | Tokyo | Japan | 105-8470 |
| 143 | Novartis Investigative Site | Shinjuku-ku | Tokyo | Japan | 160-8582 |
| 144 | Novartis Investigative Site | Kyoto | Japan | 606-8507 | |
| 145 | Novartis Investigative Site | Okayama | Japan | 700-8558 | |
| 146 | Novartis Investigative Site | Amman | Jordan | 11941 | |
| 147 | Novartis Investigative Site | Seoul | Korea, Republic of | 03080 | |
| 148 | Novartis Investigative Site | Seoul | Korea, Republic of | 06351 | |
| 149 | Novartis Investigative Site | Utrecht | The Netherlands | Netherlands | 3508 GA |
| 150 | Novartis Investigative Site | Leiden | Netherlands | 2333 ZA | |
| 151 | Novartis Investigative Site | Nijmegen | Netherlands | 6525 GA | |
| 152 | Novartis Investigative Site | Rotterdam | Netherlands | 3015 CE | |
| 153 | Novartis Investigative Site | Oslo | Norway | 0424 | |
| 154 | Novartis Investigative Site | Wroclaw | Dolnoslaskie | Poland | |
| 155 | Novartis Investigative Site | Gliwice | Slaskie | Poland | |
| 156 | Novartis Investigative Site | Katowice | Poland | ||
| 157 | Novartis Investigative Site | Kraków | Poland | ||
| 158 | Novartis Investigative Site | Warszawa | Poland | ||
| 159 | Novartis Investigational Site | Lisboa | Portugal | ||
| 160 | Novartis Investigative Site | Porto | Portugal | ||
| 161 | Incyte Investigative Site | Ponce | Puerto Rico | 11040 | |
| 162 | Novartis Investigational Site | Bucharest | Romania | 022328 | |
| 163 | Novartis Investigational Site | Bucharest | Romania | ||
| 164 | Novartis Investigative Site | Moscow | Russian Federation | 125167 | |
| 165 | Novartis Investigative Site | Saint Petersburg | Russian Federation | 197022 | |
| 166 | Novartis Investigative Site | Riyadh | Saudi Arabia | 11211 | |
| 167 | Novartis Investigative Site | Cordoba | Andalucia | Spain | 14004 |
| 168 | Novartis Investigative Site | Sevilla | Andalucía | Spain | 41013 |
| 169 | Novartis Investigative Site | Salamanca | Castilla Y Leon | Spain | 37007 |
| 170 | Novartis Investigative Site | Barcelona | Catalunya | Spain | 08026 |
| 171 | Novartis Investigative Site | Barcelona | Catalunya | Spain | 08035 |
| 172 | Novartis Investigative Site | L'Hospitalet de Llobregat | Cataluña | Spain | 08907 |
| 173 | Novartis Investigative Site | Valencia | Comunidad Valenciana | Spain | 46010 |
| 174 | Novartis Investigative Site | Santiago de Compostela | Galicia | Spain | 15706 |
| 175 | Novartis Investigative Site | El Palmar | Murica | Spain | |
| 176 | Novartis Investigative Site | San Sebastian | Pais Vasco | Spain | 20080 |
| 177 | Novartis Investigative Site | Barcelona | Spain | 08026 | |
| 178 | Novartis Investigative Site | Las Palmas de Gran Canaria | Spain | 35012 | |
| 179 | Novartis Investigative Site | Madrid | Spain | 28006 | |
| 180 | Novartis Investigative Site | Madrid | Spain | 28041 | |
| 181 | Novartis Investigative Site | Göteborg | Sweden | SE-413 45 | |
| 182 | Novartis Investigative Site | Uppsala | Sweden | SE-751 85 | |
| 183 | Novartis Investigative Site | Basel | Switzerland | 4031 | |
| 184 | Novartis Investigative Site | Zürich | Switzerland | 8091 | |
| 185 | Novartis Investigative Site | Ankara | Turkey | 06100 | |
| 186 | Novartis Investigative Site | Ankara | Turkey | 06460 | |
| 187 | Novartis Investigative Site | Antalya | Turkey | 07100 | |
| 188 | Novartis Investigative Site | Glasgow | United Kingdom | G51 4TF | |
| 189 | Novartis Investigative Site | London | United Kingdom | NW1 2PQ | |
| 190 | Novartis Investigative Site | London | United Kingdom | SE5 9RS | |
| 191 | Novartis Investigative Site | Manchester | United Kingdom | M13 9WL |
Sponsors and Collaborators
- Incyte Corporation
Investigators
- Study Director: Rodica Morariu-Zamfir, Incyte Corporation
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Incyte Corporation
ClinicalTrials.gov Identifier:
NCT03112603
Other Study ID Numbers:
- INCB 18424-365 (REACH3)
- CINC424D2301
First Posted:
Apr 13, 2017
Last Update Posted:
Jun 28, 2022
Last Verified:
Jun 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Incyte Corporation
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The study was conducted at 29 countries globally. During the main treatment period participants were randomly assigned to ruxolitinib arm or Best Available Therapy(BAT) arm for 6 cycles of treatment. At the end of Cycle 6, participants in the BAT arm either crossed over to ruxolitinib treatment or entered survival follow-up Phase. |
|---|---|
| Pre-assignment Detail | A total of 404 participants were screened, of whom 72 were screen failures and 3 were not randomized for various reasons. Out of the 329 participants randomized, 6 did not receive Best Available Treatment (BAT) due to logistical reasons and 3 did not receive due to use of prohibited medications. A total of 329 patients were included in the Full Analysis Set (FAS), 165 were in the ruxolitinib arm and 164 were in the BAT arm. |
| Arm/Group Title | Ruxolitinib | Best Available Therapy | Ruxolitinib -Cross Over Period |
|---|---|---|---|
| Arm/Group Description | Ruxolitinib was administered orally twice per day at a dose of 10 mg. | Best available therapies including but not limited to extracorporeal photopheresis (ECP),low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab ,pentostatin, imatinib and ibrutinib based on investigators decision. | Participants from BAT arm at the end of cycle 6 crossed over to ruxolitinib treatment |
| Period Title: End of Randomization Period | |||
| STARTED | 165 | 164 | 0 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 165 | 164 | 0 |
| Period Title: End of Randomization Period | |||
| STARTED | 0 | 0 | 61 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 61 |
Baseline Characteristics
| Arm/Group Title | Ruxolitinib | Best Available Therapy | Total |
|---|---|---|---|
| Arm/Group Description | Ruxolitinib was administered orally twice per day at a dose of 10 mg. | Best available therapies including but not limited to extracorporeal photopheresis (ECP),low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab ,pentostatin, imatinib and ibrutinib based on investigators decision. | Total of all reporting groups |
| Overall Participants | 165 | 164 | 329 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
45.9
(15.68)
|
47.2
(16.17)
|
46.5
(15.92)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
56
33.9%
|
72
43.9%
|
128
38.9%
|
| Male |
109
66.1%
|
92
56.1%
|
201
61.1%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| White |
116
70.3%
|
132
80.5%
|
248
75.4%
|
| Black or African American |
2
1.2%
|
0
0%
|
2
0.6%
|
| Asian |
33
20%
|
21
12.8%
|
54
16.4%
|
| American Indian or Alaska Native |
2
1.2%
|
0
0%
|
2
0.6%
|
| Other |
9
5.5%
|
4
2.4%
|
13
4%
|
| Unknown |
3
1.8%
|
7
4.3%
|
10
3%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| Hispanic/Latino |
13
7.9%
|
13
7.9%
|
26
7.9%
|
| Not Hispanic/Latino |
118
71.5%
|
115
70.1%
|
233
70.8%
|
| Not Reported |
26
15.8%
|
25
15.2%
|
51
15.5%
|
| Unknown |
8
4.8%
|
11
6.7%
|
19
5.8%
|
| ECOG Performance Status (Count of Participants) | |||
| 0 |
39
23.6%
|
42
25.6%
|
81
24.6%
|
| 1 |
92
55.8%
|
82
50%
|
174
52.9%
|
| 2 |
22
13.3%
|
22
13.4%
|
44
13.4%
|
| 3 |
0
0%
|
2
1.2%
|
2
0.6%
|
| Missing |
12
7.3%
|
16
9.8%
|
28
8.5%
|
Outcome Measures
| Title | Efficacy of Ruxolitinib Versus Investigator's Choice Best Available Therapy (BAT) in Participants With Moderate or Severe SR-cGvHD Assessed by Overall Response Rate (ORR) at the Cycle 7 Day 1 Visit |
|---|---|
| Description | ORR defined as the percentage of participants in each arm demonstrating a complete response (CR) or partial response (PR) based on Chronic GvHD Disease assessments (NIH Consensus Criteria, Lee 2015) without the requirement of additional systemic therapies for an earlier progression, mixed response or non-response. Scoring of response will be relative to the organ score at the time of randomization. |
| Time Frame | Cycle 7 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) consists of all participants to whom study treatment has been assigned by randomization. |
| Arm/Group Title | Ruxolitinib | Best Available Therapy |
|---|---|---|
| Arm/Group Description | Ruxolitinib was administered orally twice per day at a dose of 10 mg. | Best available therapies including but not limited to extracorporeal photopheresis (ECP),low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab ,pentostatin, imatinib and ibrutinib based on investigators decision. |
| Measure Participants | 165 | 164 |
| Number (95% Confidence Interval) [Percentage of Participants] |
49.7
30.1%
|
25.6
15.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ruxolitinib, Best Available Therapy |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.99 | |
| Confidence Interval |
(2-Sided) 95% 1.86 to 4.80 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Rate of Participants With Clinically Relevant Improvement of the Modified Lee cGvHD Symptom Scale Score |
|---|---|
| Description | To assess improvement of symptoms based on the total symptom score (TSS); a responder is defined as having achieved a clinically relevant reduction from baseline of the TSS. Scale that consists of 30 items in 7 subscales (skin, eye, mouth, lung, nutrition, energy and psychological). Patients report their level of symptom "bother" over the previous month on a 5-point likert scale: not at all, slightly, moderately, quite a bit, or extremely. Subscale scores and the summary score range from 0 to 100, with a higher score indicating worse symptoms. |
| Time Frame | Cycle 7 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) consists of all participants to whom study treatment has been assigned by randomization. |
| Arm/Group Title | Ruxolitinib | Best Available Therapy |
|---|---|---|
| Arm/Group Description | Ruxolitinib was administered orally twice per day at a dose of 10 mg. | Best available therapies including but not limited to extracorporeal photopheresis (ECP),low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab ,pentostatin, imatinib and ibrutinib based on investigators decision. |
| Measure Participants | 165 | 164 |
| Number (95% Confidence Interval) [Percentage of Participants] |
24.2
14.7%
|
11.0
6.7%
|
| Title | Rate of Failure-free Survival (FFS) |
|---|---|
| Description | Composite time to event endpoint incorporating the following FFS events: i) relapse or recurrence of underlying disease or death due to underlying disease, ii) nonrelapse mortality, or iii) addition or initiation of another systemic therapy for chronic GvHD (cGvHD). |
| Time Frame | Baseline to last patient reached Cycle 7 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) consists of all participants to whom study treatment has been assigned by randomization. |
| Arm/Group Title | Ruxolitinib | Best Available Therapy |
|---|---|---|
| Arm/Group Description | Ruxolitinib was administered orally twice per day at a dose of 10 mg. | Best available therapies including but not limited to extracorporeal photopheresis (ECP),low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab ,pentostatin, imatinib and ibrutinib based on investigators decision. |
| Measure Participants | 165 | 164 |
| Median (95% Confidence Interval) [months] |
NA
|
5.7
|
| Title | Best Overall Response (BOR) |
|---|---|
| Description | Defined as percentage of participants who achieved an overall response (CR+PR) based on based on Chronic GvHD Disease assessments (NIH Consensus Criteria, Lee 2015) at any time point (up to Cycle 7 Day 1 or the start of additional systemic therapy for cGvHD. |
| Time Frame | up to Cycle 7 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) consists of all participants to whom study treatment has been assigned by randomization. Data reported is from start of study to Cycle 7 Day 1(data cutoff 08 May 2020). |
| Arm/Group Title | Ruxolitinib | Best Available Therapy |
|---|---|---|
| Arm/Group Description | Ruxolitinib was administered orally twice per day at a dose of 10 mg. | Best available therapies including but not limited to extracorporeal photopheresis (ECP),low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab ,pentostatin, imatinib and ibrutinib based on investigators decision. |
| Measure Participants | 165 | 164 |
| Number (95% Confidence Interval) [Percentage of Participants] |
76.4
46.3%
|
60.4
36.8%
|
| Title | ORR at End of Cycle 3 |
|---|---|
| Description | ORR defined as the percentage of participants in each arm demonstrating a complete response (CR) or partial response (PR) based on Chronic GvHD Disease assessments (NIH Consensus Criteria, Lee 2015) without the requirement of additional systemic therapies for an earlier progression, mixed response or non-response. Scoring of response will be relative to the organ score at the time of randomization. |
| Time Frame | Cycle 4 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) consists of all participants to whom study treatment has been assigned by randomization. |
| Arm/Group Title | Ruxolitinib | Best Available Therapy |
|---|---|---|
| Arm/Group Description | Ruxolitinib was administered orally twice per day at a dose of 10 mg. | Best available therapies including but not limited to extracorporeal photopheresis (ECP),low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab ,pentostatin, imatinib and ibrutinib based on investigators decision. |
| Measure Participants | 165 | 164 |
| Number (95% Confidence Interval) [Percentage of Participants] |
54.5
33%
|
31.1
19%
|
| Title | Duration of Response |
|---|---|
| Description | Assessed for responders only; response based on Chronic GvHD Disease assessments (NIH consensus criteria Lee 2015). |
| Time Frame | First response to the last patient reached C7D1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Duration of response was evaluated in patients who achieved a CR or PR at or before Cycle 7 Day 1. Data reported is from start of study to data cutoff 08 May 2020. |
| Arm/Group Title | Ruxolitinib | Best Available Therapy |
|---|---|---|
| Arm/Group Description | Ruxolitinib was administered orally twice per day at a dose of 10 mg. | Best available therapies including but not limited to extracorporeal photopheresis (ECP),low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab ,pentostatin, imatinib and ibrutinib based on investigators decision. |
| Measure Participants | 126 | 99 |
| Median (95% Confidence Interval) [Months] |
NA
|
6.2
|
| Title | Overall Survival (OS) |
|---|---|
| Description | Defined as the time from the date of randomization to the date of death due to any cause. |
| Time Frame | From the date of randomization to the date of death due to any cause up to approximately 36 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Cumulative Incidence of Non-relapse Mortality (NRM) |
|---|---|
| Description | Defined as the cumulative incidence rate from competing risk analysis for NRM from date of randomization to date of death not preceded by underlying disease relapse/recurrence. |
| Time Frame | Months 3, 6, 12, 18, and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) consists of all participants to whom study treatment has been assigned by randomization. |
| Arm/Group Title | Ruxolitinib | Best Available Therapy |
|---|---|---|
| Arm/Group Description | Ruxolitinib was administered orally twice per day at a dose of 10 mg. | Best available therapies including but not limited to extracorporeal photopheresis (ECP),low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab ,pentostatin, imatinib and ibrutinib based on investigators decision. |
| Measure Participants | 165 | 164 |
| 3 months |
6.06
3.7%
|
4.44
2.7%
|
| 6 months |
9.79
5.9%
|
6.45
3.9%
|
| 12 months |
17.10
10.4%
|
14.13
8.6%
|
| 18 months |
17.10
10.4%
|
15.12
9.2%
|
| 24 months |
20.92
12.7%
|
19.29
11.8%
|
| Title | Percentage of Participants With ≥ 50% Reduction in Daily Corticosteroid Dose at Cycle 7 Day 1 |
|---|---|
| Description | All corticosteroid dosages prescribed to the patient and all dose changes during the study will be recorded for assessment of participants with ≥ 50% reduction in daily corticosteroid dose. |
| Time Frame | Cycle 7 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) consists of all participants to whom study treatment has been assigned by randomization. |
| Arm/Group Title | Ruxolitinib | Best Available Therapy |
|---|---|---|
| Arm/Group Description | Ruxolitinib was administered orally twice per day at a dose of 10 mg. | Best available therapies including but not limited to extracorporeal photopheresis (ECP),low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab ,pentostatin, imatinib and ibrutinib based on investigators decision. |
| Measure Participants | 165 | 164 |
| Day 15 - <= Day 28 |
12.7
7.7%
|
13.9
8.5%
|
| Day 29 - <= Day 42 |
35.7
21.6%
|
34.0
20.7%
|
| Day 43 - <= Day 56 |
46.4
28.1%
|
41.4
25.2%
|
| Day 57 - <= Day 70 |
58.0
35.2%
|
47.5
29%
|
| Day 71 - <= Day 84 |
61.0
37%
|
51.1
31.2%
|
| Day 85 - <= Day 98 |
68.1
41.3%
|
53.7
32.7%
|
| Day 99 - <= Day 112 |
68.2
41.3%
|
58.6
35.7%
|
| Day 113 - <= Day 126 |
70.1
42.5%
|
63.6
38.8%
|
| Day 127 - <= Day 140 |
69.9
42.4%
|
66.4
40.5%
|
| Day 141 - <= Day 154 |
65.8
39.9%
|
67.2
41%
|
| Day 155 - <= Day 168 |
71.2
43.2%
|
69.6
42.4%
|
| Title | Percentage of Participants Successfully Tapered Off All Corticosteroids at Cycle 7 Day 1 |
|---|---|
| Description | All corticosteroid dosages prescribed to the patient and all dose changes during the study will be recorded for assessment of participants who successfully tapered off all corticosteroids. |
| Time Frame | Cycle 7 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) consists of all participants to whom study treatment has been assigned by randomization. |
| Arm/Group Title | Ruxolitinib | Best Available Therapy |
|---|---|---|
| Arm/Group Description | Ruxolitinib was administered orally twice per day at a dose of 10 mg. | Best available therapies including but not limited to extracorporeal photopheresis (ECP),low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab ,pentostatin, imatinib and ibrutinib based on investigators decision. |
| Measure Participants | 165 | 158 |
| day 1 -≤ day 28 |
2.5
1.5%
|
2.6
1.6%
|
| day 29 -≤ day 56 |
9.6
5.8%
|
5.4
3.3%
|
| day 57 -≤ day 84 |
14.0
8.5%
|
8.5
5.2%
|
| day 85 -≤ day 112 |
16.3
9.9%
|
10.3
6.3%
|
| day 113 -≤ day 140 |
19.7
11.9%
|
12.4
7.6%
|
| day 141 -≤ day 168 |
24.2
14.7%
|
16.8
10.2%
|
| day 169 -≤ day 179 |
24.1
14.6%
|
15.9
9.7%
|
| Title | Cumulative Incidence of Malignancy Relapse/Recurrence (MR) |
|---|---|
| Description | Defined as the cumulative incidence rate from competing risk analysis of MR from date of randomization to hematologic malignancy relapse/recurrence. Calculated for participants with underlying hematologic malignant disease. |
| Time Frame | At 3, 6, 12, 18, and 24 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) consists of all participants to whom study treatment has been assigned by randomization. |
| Arm/Group Title | Ruxolitinib | Best Available Therapy |
|---|---|---|
| Arm/Group Description | Ruxolitinib was administered orally twice per day at a dose of 10 mg. | Best available therapies including but not limited to extracorporeal photopheresis (ECP),low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab ,pentostatin, imatinib and ibrutinib based on investigators decision. |
| Measure Participants | 156 | 160 |
| 0 -<3 Months |
1.28
0.8%
|
1.31
0.8%
|
| 3 -<6 Months |
2.59
1.6%
|
2.65
1.6%
|
| 6 -<12 Months |
4.94
3%
|
5.80
3.5%
|
| 12 -<18 Months |
6.96
4.2%
|
5.80
3.5%
|
| 18 -<24 Months |
6.96
4.2%
|
5.80
3.5%
|
| Title | Changes in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) |
|---|---|
| Description | The mean change from baseline of the FACT-BMT questionnaire. FACTBMT is a 50-item self-report questionnaire that measures the effect of a therapy on domains including physical, functional, social/family, and emotional well-being, together with additional concerns relevant for bone marrow transplantation patients. The questions were based on 5-point Likert scale, where 0 corresponds to 'not at all' and 4 correspond to 'very much'. The higher the final score, the better the quality of life. The FACT-BMT total score range from 0 to 148. |
| Time Frame | Up to Cycle 24 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) consists of all participants to whom study treatment has been assigned by randomization. |
| Arm/Group Title | Ruxolitinib | Best Available Therapy |
|---|---|---|
| Arm/Group Description | Ruxolitinib was administered orally twice per day at a dose of 10 mg. | Best available therapies including but not limited to extracorporeal photopheresis (ECP),low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab ,pentostatin, imatinib and ibrutinib based on investigators decision. |
| Measure Participants | 165 | 164 |
| Cycle 2 Day 1 Change from Baseline |
2.35
(12.238)
|
-0.22
(14.959)
|
| Cycle 3 Day 1 Change from Baseline |
0.61
(14.389)
|
-1.82
(15.849)
|
| Cycle 4 Day 1 Change from Baseline |
2.05
(15.834)
|
-1.05
(16.147)
|
| Cycle 5 Day 1 Change from Baseline |
1.38
(14.536)
|
-0.23
(18.903)
|
| Cycle 6 Day 1 Change from Baseline |
2.73
(14.590)
|
2.53
(14.810)
|
| Cycle 7 Day 1 Change from Baseline |
3.76
(15.028)
|
0.66
(16.816)
|
| Cycle 9 Day 1 Change from Baseline |
5.26
(16.563)
|
0.07
(17.380)
|
| Cycle 12 Day 1 Change from Baseline |
7.45
(20.902)
|
2.12
(17.477)
|
| Cycle 15 Day 1 Change from Baseline |
4.92
(18.526)
|
5.14
(16.518)
|
| Cycle 18 Day 1 Change from Baseline |
2.66
(21.705)
|
1.65
(17.219)
|
| Cycle 21 Day 1 Change from Baseline |
5.31
(22.105)
|
0.90
(11.248)
|
| Cycle 24 Day 1 Change from Baseline |
10.10
(25.179)
|
15.29
(13.188)
|
| Title | Changes in EQ-5D-5L |
|---|---|
| Description | The EQ-5D-5L: a descriptive classification consisting of five dimensions of health: mobility, self-care, usual activities, anxiety/depression, and pain/discomfort (Brooks 1996). The five-level version (no problems, slight problems, moderate problems, severe problems, and extreme problems) uses a 5-point likert scale with 1 being no problems and 5 being extreme problems. |
| Time Frame | Up to Cycle 24 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) consists of all participants to whom study treatment has been assigned by randomization. |
| Arm/Group Title | Ruxolitinib | Best Available Therapy |
|---|---|---|
| Arm/Group Description | Ruxolitinib was administered orally twice per day at a dose of 10 mg. | Best available therapies including but not limited to extracorporeal photopheresis (ECP),low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab ,pentostatin, imatinib and ibrutinib based on investigators decision. |
| Measure Participants | 165 | 164 |
| Cycle 2 Day 1 Change from Baseline |
0.03
(0.214)
|
-0.01
(0.163)
|
| Cycle 3 Day 1 Change from Baseline |
0.03
(0.220)
|
-0.04
(0.259)
|
| Cycle 4 Day 1 Change from Baseline |
0.04
(0.195)
|
-0.01
(0.192)
|
| Cycle 5 Day 1 Change from Baseline |
0.02
(0.209)
|
-0.03
(0.243)
|
| Cycle 6 Day 1 Change from Baseline |
0.05
(0.229)
|
0.01
(0.186)
|
| Cycle 7 Day 1 Change from Baseline |
0.07
(0.233)
|
0.00
(0.226)
|
| Cycle 9 Day 1 Change from Baseline |
0.06
(0.215)
|
-0.02
(0.172)
|
| Cycle 12 Day 1 Change from Baseline |
0.07
(0.193)
|
0.03
(0.149)
|
| Cycle 15 Day 1 Change from Baseline |
0.05
(0.229)
|
0.04
(0.157)
|
| Cycle 18 Day 1 Change from Baseline |
0.05
(0.301)
|
-0.01
(0.136)
|
| Cycle 21 Day 1 Change from Baseline |
0.07
(0.270)
|
0.01
(0.230)
|
| Cycle 24 Day 1 Change from Baseline |
0.16
(0.315)
|
-0.01
(0.105)
|
| Title | Incidence and Severity of Adverse Events |
|---|---|
| Description | Adverse events include occurrence of any second primary malignancies, infections, physical exam findings, changes in vital signs, routine serum chemistry, hematology results, and coagulation profile. |
| Time Frame | From baseline to 30-35 days after end of treatment, up to approximately 36 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Pharmacokinetics Parameter : Cmax of Ruxolitinib |
|---|---|
| Description | Maximum Observed Plasma Concentration of ruxolitinib |
| Time Frame | Cycle 1 Day 1 and Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Pharmacokinetic analysis set (PAS) includes all subjects who provide at least one evaluable PK concentration. |
| Arm/Group Title | Ruxolitinib |
|---|---|
| Arm/Group Description | Ruxolitinib was administered orally twice per day at a dose of 10 mg. |
| Measure Participants | 20 |
| Day 1 |
167
(39.3)
|
| Day 15 |
215
(48.8)
|
| Title | Pharmacokinetics Parameter : AUC Last of Ruxolitinib |
|---|---|
| Description | Area Under the concentration- time curve up to the last measurable concentration of ruxolitinib |
| Time Frame | Cycle 1 Day 1 and Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Pharmacokinetic analysis set (PAS) includes all subjects who provide at least one evaluable PK concentration. |
| Arm/Group Title | Ruxolitinib |
|---|---|
| Arm/Group Description | Ruxolitinib was administered orally twice per day at a dose of 10 mg. |
| Measure Participants | 20 |
| Day 1 |
636
(40.8)
|
| Day 15 |
945
(56.1)
|
| Title | Pharmacokinetics Parameter : AUCinf of Ruxolitinib |
|---|---|
| Description | Area Under the Concentration-time Curve From 0 to Infinity of ruxolitinib |
| Time Frame | Cycle 1 Day 1 and Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Pharmacokinetic analysis set (PAS) includes all subjects who provide at least one evaluable PK concentration. |
| Arm/Group Title | Ruxolitinib |
|---|---|
| Arm/Group Description | Ruxolitinib was administered orally twice per day at a dose of 10 mg. |
| Measure Participants | 20 |
| Day 1 |
642
(32.7)
|
| Day 15 |
945
(16.1)
|
| Title | Pharmacokinetics Parameter : CL/F of Ruxolitinib |
|---|---|
| Description | Oral dose clearance of ruxolitinib |
| Time Frame | Cycle 1 Day 1 and Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Pharmacokinetic analysis set (PAS) includes all subjects who provide at least one evaluable PK concentration. |
| Arm/Group Title | Ruxolitinib |
|---|---|
| Arm/Group Description | Ruxolitinib was administered orally twice per day at a dose of 10 mg. |
| Measure Participants | 20 |
| Day 1 |
15.6
(32.7)
|
| Day 15 |
15.2
(20.4)
|
| Title | Pharmacokinetics Parameter : Vz/F of Ruxolitinib |
|---|---|
| Description | Apparent oral dose volume of distribution of ruxolitinib |
| Time Frame | Cycle 1 Day 1 and Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Pharmacokinetic analysis set (PAS) includes all subjects who provide at least one evaluable PK concentration. |
| Arm/Group Title | Ruxolitinib |
|---|---|
| Arm/Group Description | Ruxolitinib was administered orally twice per day at a dose of 10 mg. |
| Measure Participants | 20 |
| Day 1 |
54
(25)
|
| Day 15 |
50.9
(33.9)
|
| Title | Pharmacokinetics Parameter : Tmax of Ruxolitinib |
|---|---|
| Description | Time to reach maximum plasma concentration of ruxolitinib |
| Time Frame | Cycle 1 Day 1 and Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Pharmacokinetic analysis set (PAS) includes all subjects who provide at least one evaluable PK concentration. |
| Arm/Group Title | Ruxolitinib |
|---|---|
| Arm/Group Description | Ruxolitinib was administered orally twice per day at a dose of 10 mg. |
| Measure Participants | 20 |
| Day 1 |
0.833
|
| Day 15 |
1.00
|
| Title | Pharmacokinetics Parameter : T1/2 of Ruxolitinib |
|---|---|
| Description | Apparent terminal phase disposition half-life of ruxolitinib |
| Time Frame | Cycle 1 Day 1 and Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Pharmacokinetic analysis set (PAS) includes all subjects who provide at least one evaluable PK concentration. |
| Arm/Group Title | Ruxolitinib |
|---|---|
| Arm/Group Description | Ruxolitinib was administered orally twice per day at a dose of 10 mg. |
| Measure Participants | 20 |
| Day 1 |
2.40
(28.9)
|
| Day 15 |
2.32
(19.8)
|
| Title | Utilization of Medical Resources |
|---|---|
| Description | Percentage of subjects with at least one submission to healthcare encounter. |
| Time Frame | Baseline to last patient reached Cycle 7 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included participants who received at least one dose of drug, 6 participants in BAT arm discontinued before receiving first dose. |
| Arm/Group Title | Ruxolitinib | Best Available Therapy |
|---|---|---|
| Arm/Group Description | Ruxolitinib was administered orally twice per day at a dose of 10 mg. | Best available therapies including but not limited to extracorporeal photopheresis (ECP),low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab ,pentostatin, imatinib and ibrutinib based on investigators decision. |
| Measure Participants | 165 | 158 |
| Number [percentage of participants] |
48.5
29.4%
|
57.0
34.8%
|
Adverse Events
| Time Frame | Baseline to last patient reached Cycle 7 Day 1 | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | The current safety data reporting includes up to C7D1 which corresponds to primary efficacy analysis. BAT Participants were allowed to crossover to ruxolitinib only after C7D1. The safety analysis set included participants who received at least one dose of drug, 6 participants in BAT arm discontinued before receiving first dose. | |||
| Arm/Group Title | Ruxolitinib | Best Available Therapy | ||
| Arm/Group Description | Ruxolitinib was administered orally twice per day at a dose of 10 mg. | Best available therapies including but not limited to extracorporeal photopheresis (ECP),low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab ,pentostatin, imatinib and ibrutinib based on investigators decision. | ||
All Cause Mortality |
||||
| Ruxolitinib | Best Available Therapy | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 13/165 (7.9%) | 9/158 (5.7%) | ||
Serious Adverse Events |
||||
| Ruxolitinib | Best Available Therapy | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 55/165 (33.3%) | 58/158 (36.7%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 1/165 (0.6%) | 0/158 (0%) | ||
| Atypical haemolytic uraemic syndrome | 0/165 (0%) | 1/158 (0.6%) | ||
| Febrile neutropenia | 3/165 (1.8%) | 2/158 (1.3%) | ||
| Leukopenia | 1/165 (0.6%) | 0/158 (0%) | ||
| Pancytopenia | 0/165 (0%) | 2/158 (1.3%) | ||
| Splenic haemorrhage | 1/165 (0.6%) | 0/158 (0%) | ||
| Thrombocytopenia | 0/165 (0%) | 1/158 (0.6%) | ||
| Thrombotic microangiopathy | 0/165 (0%) | 1/158 (0.6%) | ||
| Cardiac disorders | ||||
| Acute myocardial infarction | 0/165 (0%) | 1/158 (0.6%) | ||
| Atrial flutter | 1/165 (0.6%) | 1/158 (0.6%) | ||
| Cardiac failure | 0/165 (0%) | 1/158 (0.6%) | ||
| Cardiogenic shock | 0/165 (0%) | 1/158 (0.6%) | ||
| Myocardial infarction | 0/165 (0%) | 1/158 (0.6%) | ||
| Pericardial effusion | 0/165 (0%) | 1/158 (0.6%) | ||
| Pericarditis | 0/165 (0%) | 1/158 (0.6%) | ||
| Tachycardia | 0/165 (0%) | 1/158 (0.6%) | ||
| Eye disorders | ||||
| Keratitis | 0/165 (0%) | 1/158 (0.6%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 1/165 (0.6%) | 0/158 (0%) | ||
| Abdominal pain upper | 0/165 (0%) | 1/158 (0.6%) | ||
| Diarrhoea | 0/165 (0%) | 2/158 (1.3%) | ||
| Enterocolitis | 0/165 (0%) | 1/158 (0.6%) | ||
| Gastritis | 0/165 (0%) | 1/158 (0.6%) | ||
| Gastrointestinal haemorrhage | 0/165 (0%) | 2/158 (1.3%) | ||
| Gastrointestinal ulcer | 1/165 (0.6%) | 0/158 (0%) | ||
| Haematemesis | 1/165 (0.6%) | 0/158 (0%) | ||
| Ileus | 1/165 (0.6%) | 0/158 (0%) | ||
| Intestinal obstruction | 0/165 (0%) | 1/158 (0.6%) | ||
| Large intestine perforation | 0/165 (0%) | 1/158 (0.6%) | ||
| Melaena | 1/165 (0.6%) | 0/158 (0%) | ||
| Nausea | 0/165 (0%) | 1/158 (0.6%) | ||
| Oesophagitis | 0/165 (0%) | 1/158 (0.6%) | ||
| Oral dysaesthesia | 0/165 (0%) | 1/158 (0.6%) | ||
| Pancreatitis | 0/165 (0%) | 1/158 (0.6%) | ||
| Pancreatitis acute | 1/165 (0.6%) | 0/158 (0%) | ||
| Pneumatosis intestinalis | 0/165 (0%) | 1/158 (0.6%) | ||
| Stomatitis | 1/165 (0.6%) | 0/158 (0%) | ||
| Vomiting | 0/165 (0%) | 2/158 (1.3%) | ||
| General disorders | ||||
| Asthenia | 1/165 (0.6%) | 0/158 (0%) | ||
| Catheter site haemorrhage | 1/165 (0.6%) | 0/158 (0%) | ||
| Catheter site pain | 0/165 (0%) | 1/158 (0.6%) | ||
| Fatigue | 0/165 (0%) | 1/158 (0.6%) | ||
| General physical health deterioration | 1/165 (0.6%) | 1/158 (0.6%) | ||
| Generalised oedema | 1/165 (0.6%) | 1/158 (0.6%) | ||
| Multiple organ dysfunction syndrome | 0/165 (0%) | 1/158 (0.6%) | ||
| Oedema peripheral | 1/165 (0.6%) | 0/158 (0%) | ||
| Pyrexia | 8/165 (4.8%) | 3/158 (1.9%) | ||
| Infections and infestations | ||||
| Abscess limb | 0/165 (0%) | 1/158 (0.6%) | ||
| Adenovirus reactivation | 1/165 (0.6%) | 0/158 (0%) | ||
| Bacteraemia | 1/165 (0.6%) | 0/158 (0%) | ||
| Bacterial sepsis | 0/165 (0%) | 1/158 (0.6%) | ||
| Brain abscess | 1/165 (0.6%) | 0/158 (0%) | ||
| Bronchitis | 1/165 (0.6%) | 0/158 (0%) | ||
| Bronchopulmonary aspergillosis | 2/165 (1.2%) | 4/158 (2.5%) | ||
| Clostridium difficile infection | 0/165 (0%) | 1/158 (0.6%) | ||
| Cytomegalovirus infection | 1/165 (0.6%) | 0/158 (0%) | ||
| Cytomegalovirus infection reactivation | 2/165 (1.2%) | 1/158 (0.6%) | ||
| Device related sepsis | 0/165 (0%) | 1/158 (0.6%) | ||
| Erysipelas | 1/165 (0.6%) | 0/158 (0%) | ||
| Escherichia bacteraemia | 0/165 (0%) | 1/158 (0.6%) | ||
| Escherichia infection | 0/165 (0%) | 2/158 (1.3%) | ||
| Fungal infection | 1/165 (0.6%) | 0/158 (0%) | ||
| Gastroenteritis | 0/165 (0%) | 1/158 (0.6%) | ||
| Gastroenteritis viral | 0/165 (0%) | 1/158 (0.6%) | ||
| Herpes zoster | 1/165 (0.6%) | 0/158 (0%) | ||
| Infection | 0/165 (0%) | 1/158 (0.6%) | ||
| Influenza | 0/165 (0%) | 1/158 (0.6%) | ||
| Large intestine infection | 0/165 (0%) | 1/158 (0.6%) | ||
| Liver abscess | 0/165 (0%) | 1/158 (0.6%) | ||
| Lower respiratory tract infection | 4/165 (2.4%) | 0/158 (0%) | ||
| Measles | 1/165 (0.6%) | 0/158 (0%) | ||
| Meningitis viral | 1/165 (0.6%) | 0/158 (0%) | ||
| Metapneumovirus infection | 0/165 (0%) | 1/158 (0.6%) | ||
| Mycobacterial infection | 1/165 (0.6%) | 0/158 (0%) | ||
| Oral candidiasis | 1/165 (0.6%) | 0/158 (0%) | ||
| Oral herpes | 0/165 (0%) | 1/158 (0.6%) | ||
| Pneumococcal infection | 0/165 (0%) | 1/158 (0.6%) | ||
| Pneumocystis jirovecii pneumonia | 1/165 (0.6%) | 0/158 (0%) | ||
| Pneumonia | 13/165 (7.9%) | 13/158 (8.2%) | ||
| Pneumonia bacterial | 1/165 (0.6%) | 2/158 (1.3%) | ||
| Pneumonia cytomegaloviral | 1/165 (0.6%) | 2/158 (1.3%) | ||
| Pneumonia pseudomonal | 0/165 (0%) | 2/158 (1.3%) | ||
| Pseudomonal sepsis | 0/165 (0%) | 1/158 (0.6%) | ||
| Pulmonary nocardiosis | 0/165 (0%) | 1/158 (0.6%) | ||
| Respiratory tract infection | 1/165 (0.6%) | 0/158 (0%) | ||
| Sepsis | 2/165 (1.2%) | 1/158 (0.6%) | ||
| Septic shock | 1/165 (0.6%) | 3/158 (1.9%) | ||
| Skin infection | 0/165 (0%) | 1/158 (0.6%) | ||
| Systemic infection | 1/165 (0.6%) | 1/158 (0.6%) | ||
| Tracheitis | 1/165 (0.6%) | 0/158 (0%) | ||
| Upper respiratory tract infection | 1/165 (0.6%) | 2/158 (1.3%) | ||
| Urinary tract infection | 1/165 (0.6%) | 0/158 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Infusion related reaction | 1/165 (0.6%) | 0/158 (0%) | ||
| Spinal compression fracture | 1/165 (0.6%) | 0/158 (0%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 1/165 (0.6%) | 0/158 (0%) | ||
| Gamma-glutamyltransferase increased | 1/165 (0.6%) | 0/158 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 1/165 (0.6%) | 0/158 (0%) | ||
| Dehydration | 2/165 (1.2%) | 0/158 (0%) | ||
| Hyperkalaemia | 0/165 (0%) | 1/158 (0.6%) | ||
| Hypoglycaemia | 0/165 (0%) | 1/158 (0.6%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 2/165 (1.2%) | 0/158 (0%) | ||
| Muscular weakness | 1/165 (0.6%) | 0/158 (0%) | ||
| Osteonecrosis | 0/165 (0%) | 1/158 (0.6%) | ||
| Pain in extremity | 1/165 (0.6%) | 0/158 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Basal cell carcinoma | 1/165 (0.6%) | 0/158 (0%) | ||
| Lung neoplasm | 0/165 (0%) | 1/158 (0.6%) | ||
| Post transplant lymphoproliferative disorder | 1/165 (0.6%) | 0/158 (0%) | ||
| Nervous system disorders | ||||
| Depressed level of consciousness | 1/165 (0.6%) | 0/158 (0%) | ||
| Encephalopathy | 0/165 (0%) | 1/158 (0.6%) | ||
| Epilepsy | 1/165 (0.6%) | 0/158 (0%) | ||
| Headache | 1/165 (0.6%) | 0/158 (0%) | ||
| Neuralgia | 0/165 (0%) | 1/158 (0.6%) | ||
| Neuropathy peripheral | 0/165 (0%) | 1/158 (0.6%) | ||
| Seizure | 0/165 (0%) | 2/158 (1.3%) | ||
| Somnolence | 0/165 (0%) | 1/158 (0.6%) | ||
| Spinal cord compression | 1/165 (0.6%) | 0/158 (0%) | ||
| Syncope | 1/165 (0.6%) | 0/158 (0%) | ||
| Transient ischaemic attack | 0/165 (0%) | 1/158 (0.6%) | ||
| Psychiatric disorders | ||||
| Agitation | 0/165 (0%) | 1/158 (0.6%) | ||
| Renal and urinary disorders | ||||
| Acute kidney injury | 2/165 (1.2%) | 3/158 (1.9%) | ||
| Nephrolithiasis | 0/165 (0%) | 1/158 (0.6%) | ||
| Reproductive system and breast disorders | ||||
| Vulvovaginal inflammation | 1/165 (0.6%) | 0/158 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute respiratory distress syndrome | 1/165 (0.6%) | 1/158 (0.6%) | ||
| Atelectasis | 0/165 (0%) | 1/158 (0.6%) | ||
| Dyspnoea | 2/165 (1.2%) | 2/158 (1.3%) | ||
| Hypoxia | 0/165 (0%) | 3/158 (1.9%) | ||
| Interstitial lung disease | 0/165 (0%) | 1/158 (0.6%) | ||
| Obliterative bronchiolitis | 0/165 (0%) | 1/158 (0.6%) | ||
| Organising pneumonia | 1/165 (0.6%) | 0/158 (0%) | ||
| Pleural effusion | 0/165 (0%) | 1/158 (0.6%) | ||
| Pleuritic pain | 1/165 (0.6%) | 0/158 (0%) | ||
| Pneumonitis | 1/165 (0.6%) | 1/158 (0.6%) | ||
| Pneumothorax | 2/165 (1.2%) | 0/158 (0%) | ||
| Pulmonary embolism | 2/165 (1.2%) | 3/158 (1.9%) | ||
| Pulmonary oedema | 1/165 (0.6%) | 0/158 (0%) | ||
| Respiratory failure | 2/165 (1.2%) | 0/158 (0%) | ||
| Tachypnoea | 1/165 (0.6%) | 0/158 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Toxic epidermal necrolysis | 1/165 (0.6%) | 0/158 (0%) | ||
| Social circumstances | ||||
| Loss of personal independence in daily activities | 1/165 (0.6%) | 0/158 (0%) | ||
| Vascular disorders | ||||
| Deep vein thrombosis | 1/165 (0.6%) | 1/158 (0.6%) | ||
| Hypotension | 2/165 (1.2%) | 0/158 (0%) | ||
| Poor peripheral circulation | 0/165 (0%) | 1/158 (0.6%) | ||
| Vena cava thrombosis | 0/165 (0%) | 1/158 (0.6%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Ruxolitinib | Best Available Therapy | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 145/165 (87.9%) | 116/158 (73.4%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 48/165 (29.1%) | 20/158 (12.7%) | ||
| Neutropenia | 18/165 (10.9%) | 8/158 (5.1%) | ||
| Thrombocytopenia | 18/165 (10.9%) | 13/158 (8.2%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 2/165 (1.2%) | 8/158 (5.1%) | ||
| Constipation | 12/165 (7.3%) | 8/158 (5.1%) | ||
| Diarrhoea | 17/165 (10.3%) | 19/158 (12%) | ||
| Nausea | 15/165 (9.1%) | 16/158 (10.1%) | ||
| Vomiting | 12/165 (7.3%) | 9/158 (5.7%) | ||
| General disorders | ||||
| Fatigue | 17/165 (10.3%) | 11/158 (7%) | ||
| Oedema peripheral | 11/165 (6.7%) | 14/158 (8.9%) | ||
| Pyrexia | 20/165 (12.1%) | 14/158 (8.9%) | ||
| Infections and infestations | ||||
| BK virus infection | 9/165 (5.5%) | 2/158 (1.3%) | ||
| Cytomegalovirus infection reactivation | 8/165 (4.8%) | 13/158 (8.2%) | ||
| Nasopharyngitis | 10/165 (6.1%) | 6/158 (3.8%) | ||
| Pneumonia | 6/165 (3.6%) | 10/158 (6.3%) | ||
| Upper respiratory tract infection | 13/165 (7.9%) | 11/158 (7%) | ||
| Urinary tract infection | 11/165 (6.7%) | 5/158 (3.2%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 24/165 (14.5%) | 7/158 (4.4%) | ||
| Amylase increased | 11/165 (6.7%) | 3/158 (1.9%) | ||
| Aspartate aminotransferase increased | 16/165 (9.7%) | 4/158 (2.5%) | ||
| Blood cholesterol increased | 12/165 (7.3%) | 7/158 (4.4%) | ||
| Blood creatinine increased | 23/165 (13.9%) | 7/158 (4.4%) | ||
| Gamma-glutamyltransferase increased | 14/165 (8.5%) | 5/158 (3.2%) | ||
| Lipase increased | 10/165 (6.1%) | 2/158 (1.3%) | ||
| Platelet count decreased | 17/165 (10.3%) | 9/158 (5.7%) | ||
| Metabolism and nutrition disorders | ||||
| Hypercholesterolaemia | 9/165 (5.5%) | 2/158 (1.3%) | ||
| Hyperglycaemia | 13/165 (7.9%) | 5/158 (3.2%) | ||
| Hyperkalaemia | 9/165 (5.5%) | 4/158 (2.5%) | ||
| Hypertriglyceridaemia | 16/165 (9.7%) | 13/158 (8.2%) | ||
| Hypokalaemia | 13/165 (7.9%) | 16/158 (10.1%) | ||
| Hypomagnesaemia | 6/165 (3.6%) | 11/158 (7%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 10/165 (6.1%) | 8/158 (5.1%) | ||
| Back pain | 10/165 (6.1%) | 11/158 (7%) | ||
| Myalgia | 11/165 (6.7%) | 5/158 (3.2%) | ||
| Nervous system disorders | ||||
| Headache | 13/165 (7.9%) | 12/158 (7.6%) | ||
| Tremor | 6/165 (3.6%) | 8/158 (5.1%) | ||
| Psychiatric disorders | ||||
| Insomnia | 11/165 (6.7%) | 6/158 (3.8%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 17/165 (10.3%) | 11/158 (7%) | ||
| Dyspnoea | 15/165 (9.1%) | 10/158 (6.3%) | ||
| Vascular disorders | ||||
| Hypertension | 26/165 (15.8%) | 20/158 (12.7%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Clinical Study Agreement
Results Point of Contact
| Name/Title | Incyte Corporation |
|---|---|
| Organization | Call Center |
| Phone | 1.855.463.3463 |
| medinfo@incyte.com |
Responsible Party:
Incyte Corporation
ClinicalTrials.gov Identifier:
NCT03112603
Other Study ID Numbers:
- INCB 18424-365 (REACH3)
- CINC424D2301
First Posted:
Apr 13, 2017
Last Update Posted:
Jun 28, 2022
Last Verified:
Jun 1, 2022