- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01790295
Ruxolitinib Prior to Transplant in Patients With Myelofibrosis
Exploring the Potential of Dual Kinase JAK 1/2 Inhibitor Ruxolitinib (INC424) With Reduced Intensity Allogeneic Hematopoietic Cell Transplantation in Patients With Myelofibrosis
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Toronto, Canada, M5G 2M9
- Princess Margaret Cancer Centre, University of Toronto
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Oxford, United Kingdom, OX3 9DS
- University of Oxford
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Georgia
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Atlanta, Georgia, United States, 30322
- Emory Hospital
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Illinois
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Chicago, Illinois, United States, 60611
- Northwestern University, Robert H. Lurie Comprehensive Cancer Center
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Kansas
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Westwood, Kansas, United States, 66205
- University of Kansas Cancer Center
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New York
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New York, New York, United States, 10029
- Icahn School of Medicine at Mount Sinai
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North Carolina
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Winston-Salem, North Carolina, United States, 27103
- Wake Forest Baptist Medical Center
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Ohio
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Columbus, Ohio, United States, 43210
- Ohio State University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Documented diagnosis of primary myelofibrosis according to WHO criteria or post PV myelofibrosis or post ET myelofibrosis as per IWG-MRT criteria
- Age 18-70 years
Intermediate-2/ high-risk disease as per Dynamic IPSS (DIPSS) criteria OR Intermediate-1 risk disease with one of the following additional unfavorable features known to impact the survival adversely
- Red cell transfusion dependency
- Unfavorable Karyotype
- Platelet count <100 x 109/l
- Blasts in the PB and BM ≤10% prior to study enrollment
- Availability of a suitable matched related (6/6 or 5/6) or unrelated donor (10/10 or 9/10 antigen or allele matched).
- Able to give informed written consent
- ECOG Performance status of 0-2.
- Life expectancy >3 months
- Off all MF-directed therapy including investigational agents for at least 2 weeks prior to study enrollment and recovered from all toxicities*
Adequate organ function
- Adequate renal function - creatinine <1.5 x IULN
- Adequate hepatic function - AST/ALT <2.5 x IULN, Total Bilirubin <1.5 x IULN
- Adequate hematopoietic function - Platelet ≥50 x 109/l and ANC ≥1.0 x 109/l
- LVEF >40% (MUGA or echocardiogram) Normal per Institutional standard
Adequate pulmonary function with DLCO >50%
- A patient who has been on stable dose of Ruxolitinib and has received ruxolitinib ≤6 months prior to the study entry will be considered potentially eligible for the study with the caveat that there is no evidence of loss of response (>5cm increase in spleen size from the nadir).
Exclusion Criteria:
- Any previous JAK2 inhibitor treatment prior to study enrollment, with the exception of Ruxolitinib
- Hypersensitivity to JAK inhibitor
- Clinical or laboratory evidence of cirrhosis
- Prior allogeneic transplant for any hematopoietic disorder
- >20% blast in the PB or BM prior to HCT or had leukemic transformation (>20% blasts in PB or BM any time prior to HCT)
- Syngeneic donor
- Cord Blood transplant
- Active uncontrolled infection
- H/o another malignancy within 5-years of date of HCT except h/o basal cell or squamous cell carcinoma of skin or PV or ET
- Known HIV positive
- Pregnancy at the time of BMT
- Any other concurrent illness which in investigator's opinion puts the patient at excessive risk of treatment related toxicities
- Unable to give informed consent
- Active infection with hepatitis A,B or C virus
- Subjects who require therapy with a strong CYP3A4 inhibitor prior to enrollment to this study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Ruxolitinib Pre- Hematopoietic cell transplantation (HCT)
Ruxolitinib (INC424) tablets will be started 62 days (day -67) prior to start of conditioning chemotherapy.
The starting dose of Ruxolitinib will be determined according to baseline platelet count and will be modified according to platelet count at follow-up.
The drug will be given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and will be stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion.
The drug will be supplied as 5 mg tablets.
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Ruxolitinib (INC424) tablets will be started 60 days (day -65) prior to start of conditioning chemotherapy.
The starting dose of Ruxolitinib will be determined according to baseline platelet count and will be modified according to platelet count at follow-up.
The drug will be given in the maximum tolerated dose as defined in the protocol for 56 days, followed by 4 days of taper, and will be stopped completely at the planned start of conditioning therapy (starting on day -5) i.e. 5 days prior to stem cell infusion.
The drug will be supplied as 5 mg tablets.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Percent of Participants With 100-day Survival Without Graft Failure
Time Frame: Day 100-post allogeneic stem cell transplantation
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The feasibility of combining Ruxolitinib (INC424) with a Reduced intensity conditioning (RIC) regimen likely to produce success post transplantation, success being defined as patient being alive, and without graft failure at day 100-post allogeneic stem cell transplantation (in patients who receive (a) related donor transplant and in those who receive (b) an unrelated donor transplant.
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Day 100-post allogeneic stem cell transplantation
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Time to Neutrophil Recovery
Time Frame: up to 4 years
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Neutrophil recovery will be defined as first of the three consecutive days with neutrophil count ≥0.5 x 109/l.
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up to 4 years
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Platelet Recovery
Time Frame: up to 4 years
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Platelet recovery will be defined as first of the 7 days with platelet count ≥20 x 109/l, without platelet transfusion support and both maintained for 30 days without transfusion support or myeloid cytokine support.
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up to 4 years
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Percent of Participants With Non-relapse Mortality (NRM)
Time Frame: 100 days
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NRM will be defined as death in first 30 days due to any cause, and subsequently death due to any cause without the recurrence or progression of myelofibrosis.
Cumulative incidence of NRM will be calculated taking relapse/progression as competing event.
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100 days
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Percent of Participants With Non-relapse Mortality (NRM)
Time Frame: 1-year post transplant
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NRM will be defined as death in first 30 days due to any cause, and subsequently death due to any cause without the recurrence or progression of myelofibrosis.
Cumulative incidence of NRM will be calculated taking relapse/progression as competing event.
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1-year post transplant
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Percent of Participants With Graft Versus Host Disease (GvHD)
Time Frame: 1-year post transplant
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Acute and chronic GvHD. GvHD is a potentially serious complication of allogeneic stem cell transplantation. Stage Skin Liver (bilirubin) Gut (stool output/day) 0 No GVHD rash < 2 mg/dl < 500 ml/day or persistent nausea.
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1-year post transplant
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Chimerism Studies
Time Frame: 30 days post transplant
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Will check percentage of donor versus recipient blood cells to determine efficacy of donor engraftment
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30 days post transplant
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Chimerism Studies
Time Frame: 60 days post transplant
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Will check percentage of donor versus recipient blood cells to determine efficacy of donor engraftment
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60 days post transplant
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Chimerism Studies
Time Frame: 100 days post transplant
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Will check percentage of donor versus recipient blood cells to determine efficacy of donor engraftment
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100 days post transplant
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Number of Participants With Remission Status According to IWG-MRT Criteria
Time Frame: Day 100 post transplant
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Remission status according to International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria Remission defined as: Bone marrow:* Age-adjusted normocellularity; <5% blasts; ≤grade 1 MF and Peripheral blood: Hemoglobin ≥100 g/L and <UNL; neutrophil count ≥ 1 × 109/L and <UNL; Platelet count ≥100 × 109/L and <UNL; <2% immature myeloid cells and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of extramedullary hematopoiesis (EMH) |
Day 100 post transplant
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Number of Participants With Remission Status at 6 Months Post Transplant
Time Frame: 6 months post transplant
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Remission defined as: Bone marrow:* Age-adjusted normocellularity; <5% blasts; ≤grade 1 MF† and Peripheral blood: Hemoglobin ≥100 g/L and <UNL; neutrophil count ≥ 1 × 109/L and <UNL; Platelet count ≥100 × 109/L and <UNL; <2% immature myeloid cells‡ and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH |
6 months post transplant
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Number of Participants With Remission Status at 12 Months Post Transplant
Time Frame: 12 months post transplant
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Remission defined as: Bone marrow:* Age-adjusted normocellularity; <5% blasts; ≤grade 1 MF† and Peripheral blood: Hemoglobin ≥100 g/L and <UNL; neutrophil count ≥ 1 × 109/L and <UNL; Platelet count ≥100 × 109/L and <UNL; <2% immature myeloid cells‡ and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH |
12 months post transplant
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Number of Participants With Relapse/Progression (Defined as Per IWG-MRT Criteria)
Time Frame: 1-year post transplant
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Relapse/progression defined as: Peripheral blood: Hemoglobin ≥100 g/L and <UNL; neutrophil count ≥1 × 109/L and <UNL; platelet count ≥100 × 109/L and <UNL; <2% immature myeloid cells‡ and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH or Bone marrow:* Age-adjusted normocellularity; <5% blasts; ≤grade 1 MF†, and peripheral blood: Hemoglobin ≥85 but <100 g/L and <UNL; neutrophil count ≥1 × 109/L and <UNL; platelet count ≥50, but <100 × 109/L and <UNL; <2% immature myeloid cells‡ and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH |
1-year post transplant
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Number of Participants With Progression-free Survival
Time Frame: 1-year post transplant
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Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
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1-year post transplant
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Number of Overall Survival
Time Frame: 1-year post transplant
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1-year post transplant
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Mean Change in the Brief Fatigue Inventory Score
Time Frame: baseline and 48 months
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Mean change in the Brief Fatigue Inventory score (BFI) from baseline to 48 months to assess impact of allogeneic stem cell transplant on myelofibrosis associated symptoms and overall quality of life.
The BFI is a 9 item scored from 0 (no fatigue) -10 (as bad as you can imagine), items are averaged with total score from 0-10, with higher score indicating more fatigue.
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baseline and 48 months
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Expression Profiling and Measurements of Cytokines Prior to Start of Ruxolitinib, Prior to Start of Chemotherapy for Conditioning
Time Frame: 30 days post transplant
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30 days post transplant
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Expression Profiling and Measurements of Cytokines Prior to Start of Ruxolitinib, Prior to Start of Chemotherapy for Conditioning
Time Frame: 100 days post transplant
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100 days post transplant
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Association of Cytokines Levels With Acute and Chronic GvHD
Time Frame: 30 days post transplant
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30 days post transplant
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Association of Cytokines Levels With Acute and Chronic GvHD
Time Frame: 100 days post transplant
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100 days post transplant
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Vikas Gupta, MD, FRCP, FRCPath, University of Toronto
- Study Chair: Adam Mead, MD, University of Oxford, John Radcliffe Hospital
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms
- Neoplasms by Site
- Bone Marrow Diseases
- Hematologic Diseases
- Hemorrhagic Disorders
- Myeloproliferative Disorders
- Blood Coagulation Disorders
- Blood Platelet Disorders
- Bone Marrow Neoplasms
- Hematologic Neoplasms
- Primary Myelofibrosis
- Thrombocytosis
- Thrombocythemia, Essential
- Polycythemia Vera
- Polycythemia
Other Study ID Numbers
- GCO 12-1809
- MPD-RC 114
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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