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Trial record 1 of 1 for:    CINC424C2301
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Safety and Efficacy of Ruxolitinib Versus Best Available Therapy in Patients With Corticosteroid-refractory Acute Graft vs. Host Disease After Allogeneic Stem Cell Transplantation (REACH2)

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ClinicalTrials.gov Identifier: NCT02913261
Recruitment Status : Active, not recruiting
First Posted : September 23, 2016
Last Update Posted : October 11, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE September 18, 2016
First Posted Date  ICMJE September 23, 2016
Last Update Posted Date October 11, 2019
Actual Study Start Date  ICMJE March 10, 2017
Actual Primary Completion Date June 24, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 21, 2016)
Overall Response Rate (ORR) [ Time Frame: 28 Days ]
ORR is defined as the proportion of patients with a best overall response defined as complete response or partial response
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02913261 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 6, 2018)
  • Durable Overall Response Rate [ Time Frame: Day 56 ]
    Proportion of all patients in each arm who achieve a complete response (CR) or partial response (PR) at Day 28 (primary endpoint) AND maintain a CR or PR at Day 56.
  • ORR [ Time Frame: Day 14 ]
    Proportion of patients who achieved OR (CR+PR) at Day 14
  • Duration of response (DOR) [ Time Frame: Up to 24 months ]
    DOR is the time from first response until acute Graft versus Host Disease (aGvHD) progression or the date of additional systemic therapies for aGvHD.
  • Cumulative steroid dose [ Time Frame: 56 Days ]
    Weekly cumulative steroid dose for each subject up to Day 56 or end of treatment
  • Overall Survival (OS) [ Time Frame: Up to 24 months ]
    OS is defined as the time from the date of randomization to the date of death due to any cause.
  • Event-free survival [ Time Frame: Up to 24 months ]
    Event-free survival, defined as the time from the date of randomization to the date of hematologic disease relapse/progression, graft failure, or death due to any cause.
  • Failure-Free survival (FFS) [ Time Frame: Up to 24 months ]
    FFS is defined as the time from the date of randomization to date of hematologic disease relapse/progression, non-relapse mortality, or addition of new systemic aGvHD treatment.
  • Non Relapse Mortality (NRM) [ Time Frame: Up to 24 months ]
    NRM is defined as the time from date of randomization to date of death not preceded by hematologic disease relapse/progression
  • Malignancy Relapse/Progression (MR) [ Time Frame: Up to 24 months ]
    MR is defined as the time from date of randomization to hematologic malignancy relapse/progression. Calculated for patients with underlying hematologic malignant disease.
  • Incidence of chronic Graft versus Host Disease (cGvHD) [ Time Frame: Up to 24 months ]
    cGvHD, defined as the diagnosis of any cGvHD including mild, moderate, severe
  • Pharmacokinetic (PK) parameter: Plasma concentration at peak (CMax) after single dose and at steady state of ruxolitinib in corticosteroid refractory acute GvHD patients [ Time Frame: 168 Days ]
    plasma concentration at peak (Cmax)Ruxolitinib after a single dose and at steady state
  • Exposure-efficacy relationship of ruxolitinib in corticosteroid refractory aGvHD [ Time Frame: 168 Days ]
    exposure-efficacy relationship of ruxolitinib in terms of concentration-effect and dose-effect (effect: overall response rate at Day 28 and durable response at Day 56; Overall survival at 6 months)
  • Patient Reported Outcomes (PROs): Functional Assesment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) [ Time Frame: Baseline, Up to 30 day follow-up visit ]
    Change in Functional Assesment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) from baseline
  • Patient Reported Outcomes (PROs): EuroQol-5D-5L change [ Time Frame: Baseline, Up to 30 day follow-up visit ]
    Change in EuroQol-5D-5D from baseline
  • Pharmacokinetic (PK) parameter: Area Under the Curve (AUC) after single dose and at steady state of ruxolitinib in corticosteroid refractory acute GvHD patients [ Time Frame: 168 Days ]
    AUC from time zero to the last measurable concentration sampling time and from time zero to infinity, and Accumulation ratio (Racc). Ruxolitinib after a single dose and at steady state. AUC at end of a dosing interval (AUC tau) at steady state.
  • Pharmacokinetic (PK) parameter: total body clearance of ruxolitinib from the plasma after single dose and at steady state of ruxolitinib in corticosteroid refractory acute GvHD patients [ Time Frame: 168 Days ]
    total body clearance of ruxolitinib from the plasma after a single dose and at steady state
  • Pharmacokinetic (PK) parameter: apparent volume of distribution during terminal phase after single dose and at steady state of ruxolitinib in corticosteroid refractory acute GvHD patients [ Time Frame: 168 Days ]
    apparent volume of distribution during terminal phase after a single dose and at steady state
  • Best Overall Response (BOR) [ Time Frame: up to day 28 ]
    Proportion of patients who achieved OR (CR+PR) at any time point up to and including Day 28 and before the start of additional systemic therapy for aGvHD.
  • Pharmacokinetic (PK) parameter: Ctough [ Time Frame: 168 Days ]
    Minimum concentration (Ctough) of ruxolitininb after a single dose and at steady state in corticosteroid refractory acute GVHD patients
Original Secondary Outcome Measures  ICMJE
 (submitted: September 21, 2016)
  • Durable Overall Response Rate [ Time Frame: Day 56 ]
    Proportion of all patients in each arm who achieve a complete response (CR) or partial response (PR) at Day 28 (primary endpoint) AND maintain a CR or PR at Day 56.
  • ORR [ Time Frame: Day 14, Day 56 ]
    Proportion of patients who achieved ORR (CR+PR) at Day 14, Day 56.
  • Duration of response (DOR) [ Time Frame: Up to 24 months ]
    DOR is the time from first response until acute Graft versus Host Disease (aGvHD) progression or the date of additional systemic therapies for aGvHD.
  • Cumulative steroid dose [ Time Frame: 56 Days ]
    Weekly cumulative steroid dose for each subject up to Day 56 or end of treatment
  • Overall Survival (OS) [ Time Frame: Up to 24 months ]
    OS is defined as the time from the date of randomization to the date of death due to any cause.
  • Event-free survival [ Time Frame: Up to 24 months ]
    Event-free survival, defined as the time from the date of randomization to the date of hematologic disease relapse/progression, graft failure, or death due to any cause.
  • Failure-Free survival (FFS) [ Time Frame: Up to 24 months ]
    FFS is defined as the time from the date of randomization to date of hematologic disease relapse/progression, non-relapse mortality, or addition of new systemic aGvHD treatment.
  • Non Relapse Mortality (NRM) [ Time Frame: Up to 24 months ]
    NRM is defined as the time from date of randomization to date of death not preceded by hematologic disease relapse/progression
  • Malignancy Relapse/Progression (MR) [ Time Frame: Up to 24 months ]
    MR is defined as the time from date of randomization to hematologic malignancy relapse/progression. Calculated for patients with underlying hematologic malignant disease.
  • Incidence of chronic Graft versus Host Disease (cGvHD) [ Time Frame: Up to 24 months ]
    cGvHD, defined as the diagnosis of any cGvHD including mild, moderate, severe
  • Pharmacokinetic (PK) parameter: Plasma concentration at peak (CMax) after single dose and at steady state of ruxolitinib in corticosteroid refractory acute GvHD patients [ Time Frame: 168 Days ]
    plasma concentration at peak (Cmax)Ruxolitinib after a single dose and at steady state
  • Exposure-efficacy relationship of ruxolitinib in corticosteroid refractory aGvHD [ Time Frame: 168 Days ]
    exposure-efficacy relationship of ruxolitinib in terms of concentration-effect and dose-effect (effect: overall response rate at Day 28 and durable response at Day 56; Overall survival at 6 months)
  • Patient Reported Outcomes (PROs): Change in Functional Assesment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) from baseline [ Time Frame: Baseline, Up to 30 day follow-up visit ]
  • Patient Reported Outcomes (PROs): Change in EuroQol-5D (EQ-5D) from baseline [ Time Frame: Baseline, Up to 30 day follow-up visit ]
  • Pharmacokinetic (PK) parameter: Area Under the Curve (AUC) after single dose and at steady state of ruxolitinib in corticosteroid refractory acute GvHD patients [ Time Frame: 168 Days ]
    AUC from time zero to the last measurable concentration sampling time and from time zero to infinity. Ruxolitinib after a single dose and at steady state
  • Pharmacokinetic (PK) parameter: total body clearance of ruxolitinib from the plasma after single dose and at steady state of ruxolitinib in corticosteroid refractory acute GvHD patients [ Time Frame: 168 Days ]
    total body clearance of ruxolitinib from the plasma after a single dose and at steady state
  • Pharmacokinetic (PK) parameter: apparent volume of distribution during terminal phase after single dose and at steady state of ruxolitinib in corticosteroid refractory acute GvHD patients [ Time Frame: 168 Days ]
    apparent volume of distribution during terminal phase after a single dose and at steady state
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Ruxolitinib Versus Best Available Therapy in Patients With Corticosteroid-refractory Acute Graft vs. Host Disease After Allogeneic Stem Cell Transplantation
Official Title  ICMJE A Phase III Randomized Open-label Multi-center Study of Ruxolitinib Versus Best Available Therapy in Patients With Corticosteroid-refractory Acute Graft vs. Host Disease After Allogeneic Stem Cell Transplantation
Brief Summary To evaluate the safety and efficacy of ruxolitinib compared to Best Available Therapy in patients with corticosteroid-refractory acute graft vs. host disease after allogeneic stem cell transplantation
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Corticosteroid Refractory Acute Graft vs Host Disease
Intervention  ICMJE
  • Drug: Ruxolitinib
    Tablet for oral use
    Other Name: INC424
  • Drug: Best Available Therapy (BAT)
    Best Available Therapy
Study Arms  ICMJE
  • Active Comparator: Ruxolitinib
    Ruxolitinib 10 mg Bis In Diem (BID)
    Intervention: Drug: Ruxolitinib
  • Active Comparator: Best Available Therapy (BAT)
    As selected by the investigator
    Intervention: Drug: Best Available Therapy (BAT)
Publications * Jagasia M, Zeiser R, Arbushites M, Delaite P, Gadbaw B, Bubnoff NV. Ruxolitinib for the treatment of patients with steroid-refractory GVHD: an introduction to the REACH trials. Immunotherapy. 2018 Apr;10(5):391-402. doi: 10.2217/imt-2017-0156. Epub 2018 Jan 10.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 27, 2019)
310
Original Estimated Enrollment  ICMJE
 (submitted: September 21, 2016)
308
Estimated Study Completion Date  ICMJE April 2, 2021
Actual Primary Completion Date June 24, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Have undergone Allogeneic Stem Cell Transplanttaion (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
  • Clinically diagnosed Grades II to IV acute GvHD as per standard criteria occurring after alloSCT requiring systemic immune suppressive therapy. Biopsy of involved organs with aGvHD is encouraged but not required for study screening.
  • Confirmed diagnosis of steroid refractory aGvHD defined as patients administered high-dose systemic corticosteroids (methylprednisolone 2 mg/kg/day [or equivalent prednisone dose 2.5 mg/kg/day]), given alone or combined with calcineurin inhibitors (CNI) and either:

    • Progressing based on organ assessment after at least 3 days compared to organ stage at the time of initiation of high-dose systemic corticosteroid +/- CNI for the treatment of Grade II-IV aGvHD, OR
    • Failure to achieve at a minimum partial response based on organ assessment after 7 days compared to organ stage at the time of initiation of high-dose systemic corticosteroid +/- CNI for the treatment of Grade II-IV aGvHD,OR
    • Patients who fail corticosteroid taper defined as fulfilling either one of the following criteria:
  • Requirement for an increase in the corticosteroid dose to methylprednisolone ≥2 mg/kg/day (or equivalent prednisone dose ≥2.5 mg/kg/day) , OR
  • Failure to taper the methylprednisolone dose to <0.5 mg/kg/day (or equivalent prednisone dose <0.6 mg/kg/day) for a minimum 7 days.

Exclusion Criteria:

  • Has received more than one systemic treatment for steroid refractory aGvHD.
  • Presence of an active uncontrolled infection including significant bacterial, fungal, viral or parasitic infection requiring treatment. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
  • Evidence of uncontrolled viral infection including Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), Human Herpes Virus-6 (HHV-6), Hepatitis Virus (HBV), or Hepatitis C Virus (HCV) based on assessment by the treating physician.
  • Presence of relapsed primary malignancy, or who have been treated for relapse after the alloHSCT was performed, or who may require rapid immune suppression withdrawal as pre-emergent treatment of early malignancy relapse.

Other protocol-defined inclusion/exclusion criteria may apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Bulgaria,   Canada,   Czechia,   Denmark,   France,   Germany,   Greece,   Hong Kong,   Israel,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Norway,   Poland,   Portugal,   Russian Federation,   Saudi Arabia,   Spain,   Sweden,   Taiwan,   Turkey,   United Kingdom
Removed Location Countries Hungary
 
Administrative Information
NCT Number  ICMJE NCT02913261
Other Study ID Numbers  ICMJE CINC424C2301
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP