RATIONALE: Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. Giving vorinostat together with lenalidomide may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat when given together with lenalidomide after autologous stem cell transplant in treating patients with multiple myeloma.

OBJECTIVES:

Primary

• To assess the dose-limiting toxicities and safety of vorinostat and lenalidomide after autologous peripheral blood stem cell transplantation in patients with multiple myeloma.
• To evaluate the overall response rate to the combination of Vorinostat (SAHA) and lenalidomide.

Secondary

• To evaluate the effect of this treatment regimen on natural killer cell activity and regulatory T cells in the post-transplant period.
• To determine preliminary clinical activity of this treatment regimen by assessing overall survival and progression-free survival of these patients.
• To obtain pilot data regarding an association between this treatment regimen and patient quality of life and circulating inflammatory cytokines.

OUTLINE: This is a dose-escalation study of vorinostat.

Patients receive oral vorinostat alone once daily on days 1-21 in course 1. For the second and subsequent courses, patients receive oral vorinostat in combination with oral lenalidomide once daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection periodically for correlative laboratory studies. Studies include functional immune assays (T-cell and natural killer cell activity and regulatory T-cell recovery) by fluorescence activated cell sorting (FACS) or ELISPOT; analysis of inflammatory markers (cytokines and catecholamines); and analysis of global H3 and H4 acetylation by immunohistochemistry.

Quality of life is assessed periodically using the Brief Pain Inventory (Short Form), The Center for Epidemiologic Studies Depression Scale (CES-D-10), a 9-item Brief Fatigue Inventory, and the FACT-G questionnaires.

After completion of study treatment, patients are followed for at least 30 days.

DISEASE CHARACTERISTICS:

• Diagnosis of multiple myeloma
• Has undergone melphalan-conditioned autologous peripheral blood stem cell transplant myeloma.

PATIENT CHARACTERISTICS:

• ECOG/WHO performance status 0-2

• ANC ≥ 1,000/mm³

• Platelet count ≥ 75,000/mm³

• Total bilirubin ≤ 2 times upper limit of normal (ULN)

• AST and ALT ≤ 2 times ULN

• Serum creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 50 mL/min

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 90 days after completion of study treatment

• No blood, sperm, or ova donation during and for ≥ 4 weeks after completion of study treatment

• Able to obtain commercially available lenalidomide via Celegene's RevAssist® program

  • Registered in the RevAssist® program
  • Willing and able to comply with the requirements of RevAssist®

• Able to swallow capsules

• No severe or uncontrolled systemic illness

• No "currently active" second malignancy, other than nonmelanoma skin cancer or carcinoma in situ of the cervix

  • Patients are not considered to have a "currently active" malignancy if they completed therapy for the malignancy, are disease free from the malignancy for > 5 years, and are considered by their physician to be at < 30% risk of relapse

• No congenital long QT syndrome

• No drug or alcohol abuse within the past 12 months

• No history of allergic reactions (including erythema nodosum) attributed to compounds of similar chemical or biologic composition to lenalidomide, thalidomide, or vorinostat

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

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• More than 4 weeks since prior class Ia, Ib, or Ic antiarrhythmic medication

• No prior HDAC inhibitor-like compounds (e.g., valproic acid) as anticancer therapy

• More than 30 days since prior HDAC inhibitor-like compounds for other indications (e.g., valproic acid for epilepsy)

• No prior gastrointestinal surgery or other procedure that may, in the opinion of the investigator, interfere with the absorption or swallowing of the study drugs

• No concurrent corticosteroids other than for physiologic maintenance treatment

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

  • Irradiated area should be as small as possible
  • Lesions within the irradiated field cannot be used for response assessment

• No concurrent use of complementary or alternative medicines that would confound the interpretation of toxicities and anticancer activity of the study drugs

• No other concurrent anticancer therapy, including chemotherapy or biologic therapy

• No other concurrent HDAC inhibitors (e.g., valproic acid)