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Trial record 18 of 150 for:    INCB018424

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)

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ClinicalTrials.gov Identifier: NCT03112603
Recruitment Status : Recruiting
First Posted : April 13, 2017
Last Update Posted : January 18, 2018
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

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
Graft-versus-host Disease (GVHD) Drug: Ruxolitinib Drug: Extracorporeal photopheresis (ECP) Drug: Low-dose methotrexate (MTX) Drug: Mycophenolate mofetil (MMF) Drug: mechanistic Target of Rapamycin (mTOR) inhibitors (everolimus or sirolimus) Drug: Infliximab Drug: Rituximab Drug: Pentostatin Drug: Imatinib Drug: Ibrutinib Phase 3

Access to an investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 324 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 : June 23, 2017
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : January 2022


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 Name: Jakafi, INCB018424
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.



Primary Outcome Measures :
  1. 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 [ Time Frame: Cycle 7 Day 1 (from baseline to Day 168) ]
    ORR defined as the percentage of participants in each arm demonstrating a complete response (CR) or partial response (PR) based on NIH Consensus Criteria 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 :
  1. Rate of failure-free survival (FFS) [ Time Frame: From baseline to end of study treatment, up to 36 months ]
    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).

  2. Change in the modified Lee cGvHD symptom scale score [ Time Frame: Cycle 7 Day 1 (from baseline to Day 168) ]
    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.

  3. Best overall response (BOR) [ Time Frame: From baseline to crossover or end of treatment up to 36 months ]
    Defined as percentage of participants who achieved an overall response (CR+PR) based on NIH consensus criteria at any time point (up to Cycle 7 Day 1 or the start of additional systemic therapy for cGvHD).

  4. ORR at end of Cycle 3 [ Time Frame: Cycle 4 Day 1 (from baseline to Day 84) ]
    Percentage of participants who achieved an overall response (CR+PR) based on NIH consensus criteria at Cycle 4 Day 1.

  5. Duration of response [ Time Frame: Time from first response until GvHD progression or death, up to approximately 36 months ]
    Assessed for responders only; response based on NIH consensus criteria.

  6. Overall survival (OS) [ Time Frame: 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.

  7. Cumulative incidence of non-relapse mortality (NRM) [ Time Frame: Months 1, 2, 6, 12, 18, and 24 ]
    Defined as date of randomization to date of death not preceded by underlying disease relapse/recurrence.

  8. Percentage of participants with ≥ 50% reduction in daily corticosteroid dose at Cycle 7 Day 1 [ Time Frame: Cycle 7 Day 1 (from baseline to Day 168) ]
    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.

  9. Percentage of participants successfully tapered off all corticosteroids at Cycle 7 Day 1 [ Time Frame: Cycle 7 Day 1 (from baseline to Day 168) ]
    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.

  10. Cumulative incidence of malignancy relapse/recurrence (MR) [ Time Frame: At 3, 6, 12, 18, and 24 months ]
    Defined as the time from date of randomization to hematologic malignancy relapse/recurrence. Calculated for participants with underlying hematologic malignant disease.

  11. Changes in Functional Assessment of Cancer therapy - Bone Marrow Transplantation (FACT-BMT) [ Time Frame: From baseline to end of treatment, up to 36 months ]
    FACT-BMT will be administered to measure symptoms and quality of life for patients affected by cGvHD, and potential changes over time.

  12. Changes in EQ-5D [ Time Frame: From baseline to end of treatment, up to 36 months ]
    EQ-5D will be administered to measure symptoms and quality of life for patients affected by cGvHD, and potential changes over time.

  13. Incidence and severity of adverse events [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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/mm^3 and platelet count > 25,000/ mm^3
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03112603


Contacts
Contact: Incyte Corporation Call Center (US) 1.855.463.3463 medinfo@incyte.com
Contact: Novartis Pharmaceuticals +41613241111 trialandresults.registries@novartis.com

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Sponsors and Collaborators
Incyte Corporation
Investigators
Study Director: Fitzroy Dawkins, MD Incyte Corporation

Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT03112603     History of Changes
Other Study ID Numbers: INCB 18424-365 (REACH3)
CINC424D2301 ( Other Identifier: Novartis Pharmaceuticals )
First Posted: April 13, 2017    Key Record Dates
Last Update Posted: January 18, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
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:
Graft-versus-host disease (GvHD)
Chronic GvHD (cGvHD)
steroid-refractory
ruxolitinib
Janus kinase inhibitor

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Rituximab
Methotrexate
Everolimus
Sirolimus
Mycophenolic Acid
Pentostatin
Infliximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Nucleic Acid Synthesis Inhibitors
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antibiotics, Antitubercular
Antitubercular Agents