Ruxolitinib Prior to Transplant in Patients With Myelofibrosis
Information source: Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Primary Myelofibrosis; Post Polycythemia Vera Myelofibrosis; Post Essential Thrombocythemia Myelofibrosis
Intervention: Ruxolitinib Pre- Hematopoietic cell transplantation (HCT) (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: John Mascarenhas Official(s) and/or principal investigator(s): John Mascarenhas, MD, Principal Investigator, Affiliation: Icahn School of Medicine at Mount Sinai Vikas Gupta, MD, FRCP, FRCPath, Study Chair, Affiliation: University of Toronto Adam Mead, MD, Study Chair, Affiliation: University of Oxford, John Radcliffe Hospital
Summary
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.
Clinical Details
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
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Assessment of 100-day survival without graft failure
Secondary outcome: Neutrophil recoveryplatelet recovery Non-relapse mortality (NRM) Non-relapse mortality (NRM) Acute and chronic GvHD Chimerism studies Chimerism studies Chimerism studies Remission status according to IWG-MRT criteria Remission status according to IWG-MRT criteria Remission status according to IWG-MRT criteria Relapse/progression (defined as per IWG-MRT criteria) Progression-free survival Overall Survival Impact of allogeneic stem cell transplant on myelofibrosis associated symptoms and overall quality of life Expression profiling and measurements of cytokines prior to start of Ruxolitinib, prior to start of chemotherapy for conditioning Expression profiling and measurements of cytokines prior to start of Ruxolitinib, prior to start of chemotherapy for conditioning Association of cytokines levels with acute and chronic GvHD Association of cytokines levels with acute and chronic GvHD
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
Minimum age: 18 Years.
Maximum age: 70 Years.
Gender(s): Both.
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
Locations and Contacts
Princess Margaret Cancer Centre, University of Toronto, Toronto M5G 2M9, Canada; Recruiting Vikas Gupta, MD, FRCP, FRCPath, Phone: 416-946-4521, Email: vikas.gupta@uhn.ca Vikas Gupta, MD, FRCP, FRCPath, Principal Investigator
Chaim Sheba Medical Center, Ramat Gan 52621, Israel; Not yet recruiting Arnon Nagler, MD, MSc, Phone: 03-5305830D, Email: a.nagler@sheba.health.gov.il Arnon Nagler, MD, MSc, Principal Investigator
University of Florence, Florence 85 - 50135, Italy; Not yet recruiting Alessandro Vannucchi, MD, Phone: 39-055-7947-688, Email: a.vannucchi@unifi.it Alessandro Vannucchi, MD, Principal Investigator
University of Oxford, Oxford OX3 9DS, United Kingdom; Not yet recruiting Adam Mead, MD, Phone: 44 (0) 1865 222325, Email: adam.mead@imm.ox.ac.uk Adam Mead, MD, Principal Investigator
Mayo Clinic, Scottsdale, Arizona 85259, United States; Recruiting Clinical Trials Office All Mayo Clinic Locations, Phone: 507-538-7623 Ruben A Mesa, MD, Principal Investigator
Emory Hospital, Atlanta, Georgia 30322, United States; Recruiting Amelia Langston, MD, Phone: 404-778-4236, Email: alangst@emory.edu Amelia Langston, MD, Principal Investigator
University of Illinois at Chicago, Chicago, Illinois 60612, United States; Recruiting Damiano Rondelli, MD, Phone: 312-996-6179, Email: drond@uic.edu Damiano Rondelli, MD, Principal Investigator
University of Maryland, Baltimore, Maryland 21201, United States; Recruiting Saul Yanovich, MD, Phone: 410-328-1230 Saul Yanovich, MD, Principal Investigator
Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States; Recruiting John Mascarenhas, MD, Phone: 212-241-3417, Email: john.mascarenhas@mssm.edu John Mascarenhas, MD, Principal Investigator
Weill CornellMedical College, New York, New York 10065, United States; Not yet recruiting Tsiporah Shore, MD, FRCPC, FACP, Phone: 212-746-2646, Email: tbs2001@med.cornell.edu Tsiporah Shore, MD, FRCPC, FACP, Principal Investigator
Wake Forest Baptist Medical Center, Winston-Salem, North Carolina 27103, United States; Recruiting Dmitriy Berenzon, MD, Phone: 336-716-1808, Email: dberenzo@wfubmc.edu Vicki Lagerwey, Phone: 336-713-5947, Email: vlagerwe@wakehealth.edu
Ohio State University, Columbus, Ohio 43210, United States; Recruiting Rebecca Klisovic, MD, Phone: 614-293-4696, Email: mailto:Rebecca.klisovic@osumc.edu Rebecca Klisovic, MD, Principal Investigator
University of Utah, Salt Lake City, Utah 84132, United States; Not yet recruiting Josef Prchal, MD, Phone: 801-581-4220, Email: Josef.Prchal@hsc.utah.edu Josef Prchal, MD, Principal Investigator
Additional Information
Starting date: February 2013
Last updated: October 21, 2014
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