Valproic Acid in Treating Patients With Previously Treated Non-Hodgkin Lymphoma, Hodgkin Lymphoma, or Chronic Lymphocytic Leukemia

Epigenetic Therapy With Valproic Acid, an HDAC Inhibitor, in Refractory/Relapsed Non-Hodgkin Lymphoma, Hodgkin's Disease and CLL

RATIONALE: Valproic acid may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It may also help cancer cells become more like normal cells, and grow and spread more slowly.

PURPOSE: This phase II trial is studying how well valproic acid works in treating patients with previously treated non-Hodgkin Lymphoma, Hodgkin lymphoma, or chronic lymphocytic leukemia.

OBJECTIVES:

• To determine if valproic acid has a response rate of ≥ 20% in patients with previously treated relapsed or refractory non-Hodgkin lymphoma, Hodgkin lymphoma, or chronic lymphocytic leukemia.
• To determine if treatment with valproic acid leads to measurable levels of histone acetylation in peripheral blood.

OUTLINE: Patients are stratified according to disease diagnosis (indolent non-Hodgkin lymphoma [NHL] vs. aggressive NHL and Hodgkin lymphoma). Valproic acid doses are adjusted until therapeutic level is achieved.

Patients receive oral valproic acid daily for 3 weeks. Treatment repeats every 3 weeks for at least 2 courses and up to 2 years in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically. Samples are analyzed for valproic acid levels; and hyperacetylation (caused by the valproic acid N-terminals of the histones H3 and H4) via western blot.

DISEASE CHARACTERISTICS:

• Diagnosis of relapsed or refractory Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), or chronic lymphocytic leukemia (CLL )

• Patient must have evaluable or measurable disease

• Have failed prior treatment, as evidenced by 1 of the following:

  • Aggressive NHL

    • Failed at least 1 regimen containing rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) (unless anthracyclines are contraindicated) in addition to another salvage regimen (unless it is determined by the treating physician that it is to the patient's best interest to receive valproic acid after the first relapse)

  • Hodgkin lymphoma

    • Failed ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) and received salvage chemotherapy with at least 1 salvage combination regimen

  • Indolent or low-grade lymphoma

    • Failed at least 1 combination regimen containing rituximab (patients who are intolerant to the available therapies or have contraindications for them are eligible for the study)

• No CNS involvement by lymphoma

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Absolute granulocyte count ≥ 1,000/mm^3
• Platelet count ≥ 50,000/µL
• AST and ALT ≤ 3 times upper limit of normal
• Creatinine ≤ 2.0 mg/dL
• Bilirubin ≤ 1.5 mg/dL
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• More than 14 days since prior anticancer treatment
• Prior high-dose chemotherapy with transplant allowed
• No prior valproic acid
• No concurrent corticosteroids