Trial record 4 of 13 for:    Polycythemia Vera | Open Studies | NIH, U.S. Fed

Ruxolitinib Prior to Transplant in Patients With Myelofibrosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Mount Sinai School of Medicine
Sponsor:
Collaborators:
Myeloproliferative Disorders-Research Consortium
Incyte Corporation
Novartis
Information provided by (Responsible Party):
John Mascarenhas, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT01790295
First received: February 8, 2013
Last updated: October 21, 2014
Last verified: October 2014
  Purpose

The purpose of this study is to find out if giving the study drug Ruxolitinib (INC424) prior to a combination of other chemotherapeutic drugs (Fludarabine and Busulfan) before infusing another person's hematopoietic stem cells (bone marrow transplantation) will be successful in people who have advanced primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocythemia myelofibrosis (PET-MF), collectively known as myelofibrosis (MF). MF is a disorder in which bone marrow tissue develops in abnormal sites because the bone marrow itself undergoes fibrosis or scarring. This study plans to evaluate whether adding the drug Ruxolitinib will further aid in reducing pre-transplant spleen size, improve physical performance levels and reduce adverse events (side effects) related to the transplant. Ruxolitinib is a drug that is approved by the FDA for the treatment of patients with advanced forms of myelofibrosis. Using Ruxolitinib prior to stem cell transplantation is experimental.


Condition Intervention Phase
Primary Myelofibrosis
Post Polycythemia Vera Myelofibrosis
Post Essential Thrombocythemia Myelofibrosis
Drug: Ruxolitinib Pre- Hematopoietic cell transplantation (HCT)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Exploring the Potential of Dual Kinase JAK 1/2 Inhibitor Ruxolitinib (INC424) With Reduced Intensity Allogeneic Hematopoietic Cell Transplantation in Patients With Myelofibrosis

Resource links provided by NLM:


Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:
  • Assessment of 100-day survival without graft failure [ Time Frame: Day 100-post allogeneic stem cell transplantation ] [ Designated as safety issue: No ]
    To determine the feasibility of combining Ruxolitinib (INC424) with a 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.


Secondary Outcome Measures:
  • Neutrophil recovery [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
    Neutrophil recovery will be defined as first of the three consecutive days with neutrophil count ≥0.5 x 109/l.

  • platelet recovery [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
    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.

  • Non-relapse mortality (NRM) [ Time Frame: 100 days ] [ Designated as safety issue: No ]
    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.

  • Non-relapse mortality (NRM) [ Time Frame: 1-year post transplant ] [ Designated as safety issue: No ]
    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.

  • Acute and chronic GvHD [ Time Frame: 1-year post transplant ] [ Designated as safety issue: No ]
  • Chimerism studies [ Time Frame: 30 days post transplant ] [ Designated as safety issue: No ]
    Will check percentage of donor versus recipient blood cells to determine efficacy of donor engraftment

  • Chimerism studies [ Time Frame: 60 days post transplant ] [ Designated as safety issue: No ]
    Will check percentage of donor versus recipient blood cells to determine efficacy of donor engraftment

  • Chimerism studies [ Time Frame: 100 days post transplant ] [ Designated as safety issue: No ]
    Will check percentage of donor versus recipient blood cells to determine efficacy of donor engraftment

  • Remission status according to IWG-MRT criteria [ Time Frame: Day 100 post transplant ] [ Designated as safety issue: No ]
  • Remission status according to IWG-MRT criteria [ Time Frame: 6 months post transplant ] [ Designated as safety issue: No ]
  • Remission status according to IWG-MRT criteria [ Time Frame: 12 months post transplant ] [ Designated as safety issue: No ]
  • Relapse/progression (defined as per IWG-MRT criteria) [ Time Frame: 1-year post transplant ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: 1-year post transplant ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: 1-year post transplant ] [ Designated as safety issue: No ]
  • Impact of allogeneic stem cell transplant on myelofibrosis associated symptoms and overall quality of life [ Time Frame: up to 48 months ] [ Designated as safety issue: No ]
  • Expression profiling and measurements of cytokines prior to start of Ruxolitinib, prior to start of chemotherapy for conditioning [ Time Frame: 30 days post transplant ] [ Designated as safety issue: No ]
  • Expression profiling and measurements of cytokines prior to start of Ruxolitinib, prior to start of chemotherapy for conditioning [ Time Frame: 100 days post transplant ] [ Designated as safety issue: No ]
  • Association of cytokines levels with acute and chronic GvHD [ Time Frame: 30 days post transplant ] [ Designated as safety issue: No ]
  • Association of cytokines levels with acute and chronic GvHD [ Time Frame: 100 days post transplant ] [ Designated as safety issue: No ]

Estimated Enrollment: 86
Study Start Date: February 2013
Estimated Study Completion Date: February 2021
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Ruxolitinib Pre- Hematopoietic cell transplantation (HCT)
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:
  • Ruxolitinib \Pre- Hematopoietic cell transplantation (HCT)
  • INC424

Detailed Description:

A two- stage Simon Phase II study will be conducted in each of two groups of patients: related and unrelated donor transplants. In each donor transplant group, the first stage of this design will include 11 patients evaluated for death or graft failure by 100 days post-transplant. In each stratum, we will enroll additional patients (up to 20%) of stratum total to take into account exclusions due to donor failure (such as donor deemed unsuitable for stem cell donation due to medical or other reasons) only. Those patients who have toxicities related to Ruxolitinib and not been able to reach HCT due to these toxicities will be included in the estimation of overall failure rates. Only those patients who are excluded based on donor related issues without any regimen related complications will be excluded from the estimation of failure rates. However, all data on these patients will be reported.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

    1. Red cell transfusion dependency
    2. Unfavorable Karyotype
    3. 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01790295

Locations
United States, Arizona
Mayo Clinic Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Clinical Trials Office All Mayo Clinic Locations    507-538-7623      
Principal Investigator: Ruben A Mesa, MD         
United States, Georgia
Emory Hospital Recruiting
Atlanta, Georgia, United States, 30322
Contact: Amelia Langston, MD    404-778-4236    alangst@emory.edu   
Principal Investigator: Amelia Langston, MD         
United States, Illinois
University of Illinois at Chicago Recruiting
Chicago, Illinois, United States, 60612
Contact: Damiano Rondelli, MD    312-996-6179    drond@uic.edu   
Principal Investigator: Damiano Rondelli, MD         
United States, Maryland
University of Maryland Recruiting
Baltimore, Maryland, United States, 21201
Contact: Saul Yanovich, MD    410-328-1230      
Principal Investigator: Saul Yanovich, MD         
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: John Mascarenhas, MD    212-241-3417    john.mascarenhas@mssm.edu   
Principal Investigator: John Mascarenhas, MD         
Weill CornellMedical College Not yet recruiting
New York, New York, United States, 10065
Contact: Tsiporah Shore, MD, FRCPC, FACP    212-746-2646    tbs2001@med.cornell.edu   
Principal Investigator: Tsiporah Shore, MD, FRCPC, FACP         
United States, North Carolina
Wake Forest Baptist Medical Center Recruiting
Winston-Salem, North Carolina, United States, 27103
Contact: Dmitriy Berenzon, MD    336-716-1808    dberenzo@wfubmc.edu   
Contact: Vicki Lagerwey    336-713-5947    vlagerwe@wakehealth.edu   
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Rebecca Klisovic, MD    614-293-4696    mailto:Rebecca.klisovic@osumc.edu   
Principal Investigator: Rebecca Klisovic, MD         
United States, Utah
University of Utah Not yet recruiting
Salt Lake City, Utah, United States, 84132
Contact: Josef Prchal, MD    801-581-4220    Josef.Prchal@hsc.utah.edu   
Principal Investigator: Josef Prchal, MD         
Canada
Princess Margaret Cancer Centre, University of Toronto Recruiting
Toronto, Canada, M5G 2M9
Contact: Vikas Gupta, MD, FRCP, FRCPath    416-946-4521    vikas.gupta@uhn.ca   
Principal Investigator: Vikas Gupta, MD, FRCP, FRCPath         
Israel
Chaim Sheba Medical Center Not yet recruiting
Ramat Gan, Israel, 52621
Contact: Arnon Nagler, MD, MSc    03-5305830D    a.nagler@sheba.health.gov.il   
Principal Investigator: Arnon Nagler, MD, MSc         
Italy
University of Florence Not yet recruiting
Florence, Italy, 85 - 50135
Contact: Alessandro Vannucchi, MD    39-055-7947-688    a.vannucchi@unifi.it   
Principal Investigator: Alessandro Vannucchi, MD         
United Kingdom
University of Oxford Not yet recruiting
Oxford, United Kingdom, OX3 9DS
Contact: Adam Mead, MD    44 (0) 1865 222325    adam.mead@imm.ox.ac.uk   
Principal Investigator: Adam Mead, MD         
Sponsors and Collaborators
John Mascarenhas
Myeloproliferative Disorders-Research Consortium
Incyte Corporation
Novartis
Investigators
Principal Investigator: John Mascarenhas, MD Mount Sinai School of Medicine
Study Chair: Vikas Gupta, MD, FRCP, FRCPath University of Toronto
Study Chair: Adam Mead, MD University of Oxford, John Radcliffe Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: John Mascarenhas, Assistant Professor, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT01790295     History of Changes
Other Study ID Numbers: GCO 12-1809, MPD-RC 114
Study First Received: February 8, 2013
Last Updated: October 21, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Mount Sinai School of Medicine:
Myelofibrosis
Stem cell transplant
Ruxolitinib

Additional relevant MeSH terms:
Polycythemia
Polycythemia Vera
Primary Myelofibrosis
Thrombocythemia, Essential
Thrombocytosis
Blood Coagulation Disorders
Blood Platelet Disorders
Bone Marrow Diseases
Hematologic Diseases
Hemorrhagic Disorders
Myeloproliferative Disorders

ClinicalTrials.gov processed this record on October 23, 2014