Itacitinib, Tacrolimus, and Sirolimus for the Prevention of GVHD in Patients With Acute Leukemia, Myelodysplastic Syndrome, or Myelofibrosis Undergoing Reduced Intensity Conditioning Donor Stem Cell Transplantation
Condition: Acute Leukemia; Hematologic and Lymphocytic Disorder; Myelodysplastic Syndrome; Primary Myelofibrosis; Secondary Myelofibrosis
MeSH terms: Leukemia; Preleukemia; Myelodysplastic Syndromes; Primary Myelofibrosis; Hematologic Diseases; Syndrome; Acute Disease
Intervention: Fludarabine; Itacitinib Adipate; Melphalan; Quality-of-Life Assessment; Questionnaire Administration; Sirolimus; Tacrolimus
Intervention description: Given via infusion; Given PO; Given IV; Ancillary studies; Ancillary studies; Given PO; Given IV or PO
Intervention MeSH terms: Sirolimus; Fludarabine; Melphalan; Mechlorethamine; Nitrogen Mustard Compounds; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 59.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      This phase IIa trial studies the side effects of itacitinib when given together with standard
      treatment (tacrolimus and sirolimus), and to see how well it works in preventing
      graft-versus-host-disease (GVHD) in patients with acute leukemia, myelodysplastic syndrome or
      myelofibrosis who are undergoing reduced intensity conditioning donor stem cell
      transplantation. GVHD is a common complication after donor stem cell transplantation,
      resulting from donor immune cells recognizing recipients' cells and attacking them. Adding
      itacitinib to tacrolimus and sirolimus may reduce the risk GVHD and ultimately improve
      overall outcome and survival after donor stem cell transplantation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Documented informed consent of the participant and/or legally authorized
             representative

               -  Assent, when appropriate, will be obtained per institutional guidelines

          -  Agreement to allow the use of archival tissue from diagnostic tumor biopsies

               -  If unavailable, exceptions may be granted with study principal investigator (PI)
                  approval

          -  Performance status: Karnofsky >= 70%

          -  Patients with neoplastic hematologic disorders with indication of allogeneic
             transplant according to the standard guidelines as follows:

               -  Acute leukemia (AL) in first complete response (CR1) or subsequent complete
                  response (CR) or active disease with bone marrow (BM) blast of < 5%

               -  Myelodysplastic syndrome (MDS) with intermediate-2 or high risk per International
                  Prognostic Scoring System (IPSS) or

               -  Myelofibrosis; primary or secondary if intermediate-2 or high risk per Dynamic
                  International Prognostic Scoring System (DIPPS)

          -  All candidates for this study must have a matched related donor (MRD) who is willing
             to donate BM or peripheral blood stem cells or an 8/8 allele matched unrelated donor
             (MUD)

          -  Total bilirubin =< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease)
             (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated.
             In case of active disease, evaluation should be done within 15 days)

          -  Aspartate aminotransferase (AST) =< 2.5 x ULN (performed within 28 days prior to day 1
             of protocol therapy unless otherwise stated. In case of active disease, evaluation
             should be done within 15 days)

          -  Alanine aminotransferase (ALT) =< 2.5 x ULN (performed within 28 days prior to day 1
             of protocol therapy unless otherwise stated. In case of active disease, evaluation
             should be done within 15 days)

          -  Creatinine clearance of >= 60 mL/min per 24 hour urine test or the Cockcroft-Gault
             formula (performed within 28 days prior to day 1 of protocol therapy unless otherwise
             stated. In case of active disease, evaluation should be done within 15 days)

          -  Left ventricular ejection fraction (LVEF) >= 50%

               -  Note: To be performed within 28 days prior to day 1 of protocol therapy

          -  If able to perform pulmonary function tests: forced expiratory volume in 1 second
             (FEV1), forced vital capacity (FVC) and diffusion capacity of the lung for carbon
             monoxide (DLCO) (diffusion capacity) >= 50% of predicted (corrected for hemoglobin).
             If unable to perform pulmonary function tests: oxygen (O2) saturation > 92% on room
             air.

               -  Note To be performed within 28 days prior to day 1 of protocol therapy

          -  Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab)
             combination (combo), hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface
             antigen negative), and syphilis (rapid plasma reagin measurement [RPR])

               -  If HCV positive, hepatitis C ribonucleic acid (RNA) quantitation must be
                  performed

          -  Meets other institutional and federal requirements for infectious disease titer
             requirements

               -  Note Infectious disease testing to be performed within 28 days prior to day 1 of
                  protocol therapy

          -  Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required

          -  Agreement by females and males of childbearing potential to use an effective method of
             birth control or abstain from heterosexual activity for the course of the study
             through at least 6 months after the last dose of protocol therapy

               -  Childbearing potential defined as not being surgically sterilized (men and women)
                  or have not been free from menses for > 1 year (women only)

        Exclusion Criteria:

          -  Chemotherapy, radiation therapy, biological therapy, and/or immunotherapy within 21
             days prior to day 1 of protocol therapy

               -  Note: Conditioning regimen within 21 days prior to day 1 of protocol therapy is
                  not considered as an exclusion criterion

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to study agent

          -  Psychological issues, no appropriate caregivers identified, or non-compliant to
             medication

          -  Uncontrolled medical or psychiatric disorders which may preclude patients to undergo
             clinical studies (Discretion of the attending physician)

          -  Active diarrhea due to inflammatory bowel disease or malabsorption syndrome

          -  Clinically significant uncontrolled illness

          -  Active, uncontrolled systemic infection (bacterial, viral, or fungal) requiring
             antibiotics

          -  Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection

          -  Diagnosis of Gilbert's disease

          -  Other active malignancy

          -  Females only: Pregnant or breastfeeding

          -  Any other condition that would, in the investigator's judgment, contraindicate the
             patient's participation in the clinical study due to safety concerns with clinical
             study procedures

          -  Prospective participants who, in the opinion of the investigator, may not be able to
             comply with all study procedures (including compliance issues related to
             feasibility/logistics)