Histone Deacetylase (HDAC) Inhibition Using Vorinostat (SAHA) After Autologous Hematopoietic Stem Cell Transplantation for High Risk Lymphoma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Must have received a BEAM (cytarabine, etoposide, melphalan, carmustine)-conditioned
autologous stem cell transplantation for any of the following high-risk lymphomas:

- Diffuse large B-cell lymphoma as defined by:

- Induction failure but with response to salvage therapy

- Relapse less than one year after completion of induction therapy

- Elevated lactate dehydrogenase (LDH) at relapse

- Stage III/IV disease at relapse

- Positive PET scan after induction or salvage therapy

- Age ≤ 75 and ≥ 60 years

- Follicular lymphoma as defined by:

- Progressive disease after two or more prior regimens

- Transformed to aggressive lymphoma but still chemotherapy sensitive

- Not felt to be a good candidate for an allogeneic transplantation

- Hodgkin lymphoma as defined by:

- Primary refractory disease

- Relapse less than one year after completion of induction therapy

- Relapse with PET-positive disease after salvage therapy

- Relapsed refractory and not felt to be a good candidate for an allogeneic
transplantation

- Mantle cell lymphoma

- Chemotherapy-sensitive disease after induction therapy

- Chemotherapy-sensitive relapsed disease and not felt to be a good candidate
for an allogeneic transplantation

- T-cell non-Hodgkin lymphoma (NHL)

- Peripheral T-cell lymphoma not otherwise specified and one or more of the
following at diagnosis:

- High LDH

- Marrow involvement

- Age > 60 years

- Low platelet count

- Relapsed chemotherapy-sensitive disease

- Angioimmunoblastic lymphadenopathy with dysproteinemia

- Anaplastic lymphoma kinase-negative anaplastic NHL

- Enteropathy-associated T-cell NHL

- Natural killer (NK)/T-cell NHL and stage III/IV disease at diagnosis

- NK blastic NHL

PATIENT CHARACTERISTICS:

- ECOG/WHO performance status 0-2

- ANC ≥ 1,000/μL

- Platelet count ≥ 75,000/μL

- Total bilirubin ≤ 1.5 mg/dL

- AST/ALT ≤ 2 x upper limit of normal (ULN)

- Serum creatinine ≤ 1.5 x ULN OR creatinine clearance ≥ 50 mL/min

- No severe or uncontrolled systemic illness

- Patients must be able to swallow capsules

- Negative pregnancy test

- Not pregnant or nursing

- Fertile patients must use at least two adequate barrier methods of contraception
during study and for 90 days after completion of study therapy

- No other malignancy within the past 5 years other than nonmelanoma skin cancer,
carcinoma in situ of the cervix, or a malignancy considered by their physician to be
at less than 30% risk of relapse

- No congenital long QT syndrome

- No significant history of uncontrolled cardiac disease (i.e., uncontrolled
hypertension, unstable angina, myocardial infarction within the past 6 months, or
uncontrolled congestive heart failure)

- No active bacterial, fungal, or viral infection

- No known HIV infection

- No active hepatitis B and/or hepatitis C infection

- No other medical condition, including mental illness or substance abuse, deemed by
the Investigator(s) to interfere with a patient's ability to sign informed consent,
cooperate and participate in the study, or interfere with the interpretation of the
results

PRIOR CONCURRENT THERAPY:

- Recovered from the majority of the toxicities from the autologous transplantation
(must have returned to their pretransplant baseline or have no greater than grade I
extramedullary toxicity [CTCAE 3.0])

- No prior treatment with a histone deacetylase (HDAC) inhibitor (e.g., depsipeptide,
MS-275, LAQ-824, belinostat, valproic acid)

- More than 4 weeks since prior and no concurrent class Ia, Ib, or Ic antiarrhythmic
drugs

- No other concurrent antineoplastic chemotherapy or biologic therapy

- No concurrent radiotherapy, unless for local control of bone pain

- Irradiated area for pain management should be as small as possible and lesions
within the irradiated field cannot be used for response

- No concurrent use of complementary or alternative medicines that would confound the
interpretation of toxicities and antitumor activity of vorinostat (SAHA)