Myeloproliferative Neoplasms Clinical Trial
Ruxolitinib Prior to Transplant in Patients With Myelofibrosis
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.
Full 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 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
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
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There are 8 Locations for this study
Atlanta Georgia, 30322, United States
Chicago Illinois, 60611, United States
Westwood Kansas, 66205, United States
New York New York, 10029, United States
Winston-Salem North Carolina, 27103, United States
Columbus Ohio, 43210, United States
Toronto , M5G 2, Canada
Oxford , OX3 9, United Kingdom
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