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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 recovery

platelet 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

Page last updated: August 23, 2015

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