Ruxolitinib Phosphate before and after Stem Cell Transplant in Treating Patients with Primary or Secondary Myelofibrosis
Ruxolitinib Phosphate before and after Stem Cell Transplant in Treating Patients with Primary or Secondary Myelofibrosis
This phase II trial studies how well ruxolitinib phosphate before and after stem cell transplant works in treating patients with primary or secondary myelofibrosis. Ruxolitinib phosphate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fludarabine and melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patients immune cells and help destroy any remaining cancer cells.
Hematologic
Phase II
Adults
Mol. targeted/Immunotherapy/Biologics
Ruxolitinib
Oluwole, Olalekan
National
Vanderbilt University
12-06-2018
Treatment
VICCCTT1863
NCT03427866
Eligibility
18 Years
BOTH
NO
Inclusion Criteria:
Participants must have pathologically confirmed primary myelofibrosis according to World Health Organization (WHO) criteria or secondary myelofibrosis as defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria * Intermediate-2/ high-risk disease as per Dynamic International Prognostic Scoring System (IPSS) (DIPSS) Plus criteria OR * Intermediate-1 risk disease defined by one of the following unfavorable features known to impact the survival adversely ** Red cell transfusion dependency ** Unfavorable karyotype ** Platelet count =
Age 18-75
Participants must be designated to undergo reduced intensity allogeneic peripheral blood (PB) or bone marrow (BM) hematopoietic stem cell transplantation
Participants who will undergo HCT from the following donor types are eligible: * 6/6 (HLA-A, B, DR) fully matched related donor * 8/8 (HLA-A, B, DR, C) fully matched unrelated donor. Matching in the unrelated setting must be at the allele level
Eastern Cooperative Oncology Group (ECOG) performance status == 60%)
Life expectancy of greater than 3 months
Able to give informed consent
Off all mycosis fungoides (MF)-directed therapy (with the exception of ruxolitinib) one week or 4 half-lives (effective), whichever is longer, prior to first dose of study treatment
No allergy to ruxolitinib in the past
For patients already receiving ruxolitinib at the time of enrollment, patients should be treated with ruxolitinib for a sufficient time to optimize spleen response or symptoms, at the discretion of the treating provider, prior to enrollment. Patients who have had prior splenectomy are eligible.
Exclusion Criteria:
Prior history of progressive multifocal leukoencephalopathy (PML)
Concomitant receipt of St. Johns wort
Hypersensitivity to any JAK inhibitor, including ruxolitinib, fedratinib, or any other JAK inhibitor
Prior allogeneic transplant for any hematopoietic disorder
Had accelerated phase or leukemic transformation (>= 10% blasts in peripheral blood [PB] or bone marrow [BM] any time prior to HCT)
Patients with uncontrolled infection (patients with stable controlled infections such as hepatitis B or human immunodeficiency virus (HIV) patients with undetectable viral load on antiviral treatment would be eligible). Patients who are actively ill and require hospitalization to treat an infection will be excluded.
History of another malignancy within 5-years of date of enrollment except those who have received definitive treatment. Definitive treatment will be defined as the use of surgery, chemotherapy or radiation for the treatment of a malignancy, which subsequently has no evidence of disease after 2 years or
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]), alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) >= 3 x institutional upper limit of normal (ULN)
Alkaline phosphatase >= 3 x institutional upper limit of normal (ULN)
Direct bilirubin > 2.0 mg/dL
Calculated creatinine clearance =
Have current or a history of congestive heart failure New York Heart Association (NYHA) class 3 or 4, or any history of documented diastolic or systolic dysfunction (left ventricular ejection fraction [LVEF]
Pregnancy at the time of enrollment
Unable to give informed consent
Have an uncontrolled intercurrent illness including, but not limited to, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Not able to take oral medication
Participants must have pathologically confirmed primary myelofibrosis according to World Health Organization (WHO) criteria or secondary myelofibrosis as defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria * Intermediate-2/ high-risk disease as per Dynamic International Prognostic Scoring System (IPSS) (DIPSS) Plus criteria OR * Intermediate-1 risk disease defined by one of the following unfavorable features known to impact the survival adversely ** Red cell transfusion dependency ** Unfavorable karyotype ** Platelet count =
Age 18-75
Participants must be designated to undergo reduced intensity allogeneic peripheral blood (PB) or bone marrow (BM) hematopoietic stem cell transplantation
Participants who will undergo HCT from the following donor types are eligible: * 6/6 (HLA-A, B, DR) fully matched related donor * 8/8 (HLA-A, B, DR, C) fully matched unrelated donor. Matching in the unrelated setting must be at the allele level
Eastern Cooperative Oncology Group (ECOG) performance status == 60%)
Life expectancy of greater than 3 months
Able to give informed consent
Off all mycosis fungoides (MF)-directed therapy (with the exception of ruxolitinib) one week or 4 half-lives (effective), whichever is longer, prior to first dose of study treatment
No allergy to ruxolitinib in the past
For patients already receiving ruxolitinib at the time of enrollment, patients should be treated with ruxolitinib for a sufficient time to optimize spleen response or symptoms, at the discretion of the treating provider, prior to enrollment. Patients who have had prior splenectomy are eligible.
Exclusion Criteria:
Prior history of progressive multifocal leukoencephalopathy (PML)
Concomitant receipt of St. Johns wort
Hypersensitivity to any JAK inhibitor, including ruxolitinib, fedratinib, or any other JAK inhibitor
Prior allogeneic transplant for any hematopoietic disorder
Had accelerated phase or leukemic transformation (>= 10% blasts in peripheral blood [PB] or bone marrow [BM] any time prior to HCT)
Patients with uncontrolled infection (patients with stable controlled infections such as hepatitis B or human immunodeficiency virus (HIV) patients with undetectable viral load on antiviral treatment would be eligible). Patients who are actively ill and require hospitalization to treat an infection will be excluded.
History of another malignancy within 5-years of date of enrollment except those who have received definitive treatment. Definitive treatment will be defined as the use of surgery, chemotherapy or radiation for the treatment of a malignancy, which subsequently has no evidence of disease after 2 years or
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]), alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) >= 3 x institutional upper limit of normal (ULN)
Alkaline phosphatase >= 3 x institutional upper limit of normal (ULN)
Direct bilirubin > 2.0 mg/dL
Calculated creatinine clearance =
Have current or a history of congestive heart failure New York Heart Association (NYHA) class 3 or 4, or any history of documented diastolic or systolic dysfunction (left ventricular ejection fraction [LVEF]
Pregnancy at the time of enrollment
Unable to give informed consent
Have an uncontrolled intercurrent illness including, but not limited to, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Not able to take oral medication
