Post Transplant Cyclophosphamide (Cytoxan) for GvHD Prophylaxis
Condition: Leukemia; Lymphoma; Myelodysplastic Syndrome; Myelofibrosis; Severe Aplastic Anemia; Allogeneic Transplant
MeSH terms: Lymphoma; Leukemia; Preleukemia; Myelodysplastic Syndromes; Primary Myelofibrosis; Anemia, Aplastic
Intervention: Cyclophosphamide
Intervention MeSH terms: Cyclophosphamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 39.0
Sex: All
Minimum age: 19 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: acute myeloid leukemia; AML; acute lymphoblastic leukemia; ALL; chronic myeloid leukemia; CML; chronic lymphocytic leukemia; CLL; non-Hodgkin lymphoma; NHL; Hodgkin lymphoma; HL; myelodysplastic syndrome; MDS; myelofibrosis; severe aplastic anemia

Summary:

      The main purpose of this study is to assess the effects of cyclophosphamide (cytoxan) in the
      post transplant setting to prevent onset of acute graft-versus-host disease (GVHD). The
      primary objective is to determine the incidence of grade II-IV acute GVHD following
      Allogeneic (allo) Hematopoeitic Cell Transplant (HCT) using post-transplant cyclophosphamide
      (cytoxan) for patients with human leukocyte antigen (HLA) matched unrelated (MUD) and
      mismatched unrelated (MMUD) donors. Other objectives for this study will be the determination
      of disease-free survival (DFS) and overall survival (OS) following allo HCT and assess the
      safety of post-transplant cyclophosphamide (cytoxan) for MUD and MMUD transplantation.
      Disease recurrence and time to recurrence in patients receiving post-transplant
      cyclophosphamide compared to historical control without post-transplant cyclophosphamide
      (cytoxan) will also be evaluated. Other objectives will be to determine the time of onset,
      severity, responsiveness to treatment, organs involved of acute and chronic GVHD as well as
      observation of Immune Reconstitution over time.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Disease Criteria: patients must meet diagnostic criteria of acute myeloid leukemia
             (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), chronic
             lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL),
             myelodysplastic syndrome (MDS), myelofibrosis, or severe aplastic anemia. Patients
             will be allowed on study if they are deemed eligible for allo HCT regardless of
             remission status.

          -  Age Criteria: 19 to 65 years in age.

          -  Organ Function Criteria: All organ function testing should be done within 28 days of
             study registration.

          -  Cardiac: Left ventricular ejection fraction (LVEF) ≥ 50% by MUGA (Multi Gated
             Acquisition) scan or echocardiogram.

          -  Pulmonary: FEV1 (Forced expiratory volume in 1 second) and FVC (Forced vital capacity)
             ≥ 50% predicted, DLCO (diffusing capacity of the lung for carbon monoxide) (corrected
             for hemoglobin) ≥ 50% of predicted.

          -  Renal: The estimated creatinine clearance (CrCl) must be equal or greater than 60
             mL/min/1.73 m2 as calculated by the Cockcroft-Gault Formula:

        CrCl=(140-age) x weight(kg) x 0.85 (if female)/72 x serum creatinine (mg/dL)

          -  Hepatic:

               -  Serum bilirubin 1.5 upper limit of normal (ULN)

               -  Aspartate transaminase (AST)/alanine transaminase (ALT) 2.5 ULN

               -  Alkaline phosphatase 2.5 ULN

          -  Performance status: Karnofsky ≥ 70%.,

          -  Patient must be informed of the investigational nature of this study in accordance
             with institutional and federal guidelines and have the ability to provide written
             informed consent prior to initiation of any study-related procedures, and ability, in
             the opinion of the principal investigator, to comply with all the requirements of the
             study.

          -  Patient has a suitable and willing HLA-8/8 matched or 6/8 mismatched (at one allele)
             unrelated donor identified.

        Exclusion Criteria:

          -  Non-compliant to medications.

          -  No appropriate caregivers identified.

          -  HIV1 (Human Immunodeficiency Virus-1) or HIV2 positive

          -  Uncontrolled medical or psychiatric disorders.

          -  Uncontrolled infections, defined as positive blood cultures within 72 hours of study
             entry, or evidence of progressive infection by imaging studies such as chest CT scan
             within 14 days of registration.

          -  Active central nervous system (CNS) leukemia.

          -  Preceding allogeneic HSCT.

          -  Pregnancy or Breastfeeding.