The proposed research study is to test the drug vorinostat, in a new use as an additional medication, with other standard treatments for the prevention of severe acute graft versus host disease (GVHD).

If this treatment is safe and effective, when combined with a reduced intensity transplant, the research may achieve a more effective therapy for patients with high-risk, blood cell related cancers.

All subjects will receive an identical, known treatment to test if the treatment is safe and effective (a phase II trial). For patients to take part they must have a high-risk, blood cell cancer, be suitable candidates to receive a reduced intensity transplant and have a matched, related donor.

Adult subjects (age 18 years and older) will be considered as subjects provided, as detailed in the protocol, they meet additional criteria and are not excluded from participating. About fifty (50) subjects will be enrolled in this study at the University of Michigan.

Patients who receive blood stem cell transplants (HSCT), also called bone marrow transplants, to treat their cancer are at risk for serious complications, which may sometimes be fatal. The more common, serious ones are relapse (return of their disease), body organ injury from the intensity of the chemotherapy given prior to their transplant, and a serious complication called graft versus host disease (GVHD). GVHD is a form of rejection, where the transplanted cells of the donor attack the recipient's body as foreign, and do damage to organs and tissues.

To decrease the side effects of the chemotherapy given before a transplant, reduced intensity treatment plans(regimens)have recently been developed at a number of transplant centers. A decrease in the side effects of chemotherapy (called toxicities) has been achieved; however, this success with "less intensive" treatments has been partially offset by less successful results in controlling the patient's cancer.

As mentioned above, GVHD is a form of transplant rejection. GVHD can affect the digestive system, skin, liver and other body systems. GVHD can increase the risk of infection. After a matched, related donor stem cell transplant, GVHD when severe, is a major cause of discomfort, organ damage, and even death. When a graft vs host reaction develops, but is kept under control, studies show there may be a beneficial graft versus tumor effect, helping to destroy tumor cells in the patient, and thus providing a more effective control of their cancer.

The goal of this study is to try to maximize the potential benefits, of giving patients less intense chemotherapy to reduce the toxic effects, letting the graft vs host effect help in destroying tumor cells, but preventing acute severe GVHD by using the drug vorinostat, combined with standard medicines, to reduce the chance of serious GVHD-related complications.

Inclusion Criteria:

• Have a 7/8 or 8/8 HLA A, B, C and DR, HLA-matched related donor willing and able to donate allogeneic stem cells.
• For patients with multiple myeloma, CLL, and lymphoma: must be in CR, PR, or stable disease.
• For MDS, acute leukemia or CML: must have <20% blasts on marrow exam.
• For all other diseases: must have non-refractory disease.

and meet at least ONE of the next three criteria:

• Any patient ≥ 18 years of age with a hematological malignancy and not considered a candidate for allogeneic myeloablative transplant due to illness and/or age (≥55 years).
• Any patient ≥ 18 years of age who has relapsed following prior autologous or allogeneic transplant for a hematologic malignancy.
• Any patient ≥ 18 years of age diagnosed with a hematological malignancy for which reduced intensity transplant is institutionally preferred over myeloablative transplant (eg, chronic lymphocytic leukemia).

Exclusion Criteria:

• Less than 18 years of age.

• Currently taking any HDAC inhibitors, or have taken an HDAC inhibitor within 30 days of the trial.

• Positive serum tests for HIV, HTLV1 / HTLV2.

• Detectable hepatitis B virus (HBV), hepatitis C (HCV) or Epstein-Barr (EBV).

• Pregnancy.

• One or more of the following organ system function criteria

  • Cardiac: Ejection fraction ≤ 40%
  • Renal: Estimated or actual GFR ≤ 40 ml/min (corrected for BSA)
  • Pulmonary: FEV1, FVC, or DLCO ≤ 40% predicted
  • Hepatic: Total bilirubin ≥3 mg% and AST/ALT >5 x institutional normal for age
  • Karnofsky score ≤50 (Requires considerable assistance and frequent medical care).

• Persistent invasive infections not controlled by antimicrobial medication.

• Any physical or psychological condition that, in the opinion of the investigator, would pose unacceptable risk to the patient.