Vorinostat Plus Tacrolimus & Methotrexate to Prevent Graft vs Host Disease Following Unrelated Stem Cell Transplant
Condition: Graft vs Host Disease; Hematologic Neoplasms; Non-Neoplastic Hematologic and Lymphocytic Disorder
MeSH terms: Hematologic Neoplasms; Hematologic Diseases; Graft vs Host Disease
Intervention: Vorinostat; Tacrolimus; Methotrexate
Intervention description: administered at a dose of 100 mg orally, twice daily starting on day -10 in order to achieve steady-state prior to beginning the conditioning chemotherapy, and continued after transplant (day 0) until day +100.
Intervention MeSH terms: Methotrexate; Vorinostat; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This protocol, UMCC 2012.047, was a pilot study initially intended for 12 subjects. After
      completing enrollment of the planned 12 subjects, we are extending the study to an additional
      25 subjects. The trial will examine the safety and efficacy of the addition of vorinostat,
      the study drug, to standard medications to try to prevent or lower the risk of graft
      versus-host disease (GVHD) for recipients of unrelated (matched) donor, blood or marrow stem
      cell transplants. The transplant regimens, chosen according to current institutional policy,
      will depend upon the recipients underlying disease (their blood cancer or other blood
      disorder), previous therapy, and current health issues. GVHD prophylaxis (preventive drug
      intervention) will be the local institutional standard for post-transplant immunosuppression,
      including tacrolimus and methotrexate, plus vorinostat. Vorinostat will be given twice daily
      orally beginning 10 days prior to the recipient's transplant and continue for up to 100 days
      after transplant.
    

Eligibility criteria:

        Inclusion Criteria:

          -  A prospective patient for allogeneic HSCT for hematologic conditions, both malignant
             and non-malignant. Donor can be unrelated marrow or peripheral blood cells. A patient
             with history of CNS involvement is eligible if CNS disease is in remission at time of
             study consideration.

          -  Age between 18-75 years

          -  The donor and recipient must have an HLA-8/8 allelic match at the HLA-A, -B, -C, and
             -DRB1.

          -  Diagnosis of following diseases (subject to additional complex screening criteria)

               -  Acute Myelogenous Leukemia:

                    -  First remission (cytogenetic intermediate or high risk)

                    -  Second or subsequent remission

               -  Chronic Myelogenous Leukemia:

                    -  First, subsequent chronic phases, or atypical

                    -  Accelerated Phase

               -  Myelodysplastic syndromes

               -  Chronic Lymphocytic Leukemia

               -  Primary Myelofibrosis

               -  Mature B Cell Malignancies (including Mantle Cell Lymphoma, Follicular Lymphoma.
                  Diffuse Large B Cell Lymphoma, Non-Hodgkin Lymphoma not otherwise specified)

          -  Karnofsky (Attempt to classify a cancer patients' activities of daily life that runs
             from 0 to 100 where 100 represents perfect health and 0 represents death) >70%

          -  Life expectancy of greater than 6 months.

          -  Organ and marrow function as defined by the institutional BMT (Bone Marrow Transplant)
             program clinical practice guidelines

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             the duration of study participation.

          -  Able to swallow capsules/tablets

        Exclusion Criteria:

          -  Not a candidate for an unrelated donor allogeneic transplant conditioning regimen
             based on the current institutional BMT program clinical practice guidelines. Organ
             function criteria will be utilized per the current institutional BMT program clinical
             practice guidelines. There will be no restriction to study entry based on
             hematological parameters.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to vorinostat

          -  Undergoing a total body irradiation (TBI)-based conditioning regimen (TBI 1200 cGy)

          -  Uncontrolled illness including, but not limited to, ongoing or active infection,
             symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or
             psychiatric illness/social situations that would limit compliance with study
             requirements. Patients still under therapy for presumed or proven infection are
             eligible provided there is clear evidence (radiographic findings and/or culture
             results) that the infection is well-controlled. Patients under treatment for infection
             will be enrolled only after clearance from the PI

          -  Any medical or psychological comorbidities/conditions that would keep the patient from
             complying with the needs of the protocol and/or would markedly increase the risk of
             morbidity and mortality.

          -  Pregnant women or nursing mothers.

          -  Evidence of HIV seropositivity and/or positive PCR assay, HTLV1 / HTLV2
             seropositivity.

          -  Evidence of Hepatitis B or Hepatitis C PCR positivity.

          -  Less than 18 years of age.

          -  A history of prolonged QTc syndrome.

          -  Taking or have had prior treatment with a drug like vorinostat within the last 30
             days.