RATIONALE: AR-42 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of AR-42 in treating patients with advanced or relapsed multiple myeloma, chronic lymphocytic leukemia, or lymphoma.

PRIMARY OBJECTIVES:

I. To estimate the safety by estimating the maximum tolerated dose (MTD) and describe the dose limiting toxicity (DLT) of AR-42 administered orally three times weekly (Mon, Wed, and Fri preferred) each week for 3 weeks during each 28-day period to adults with advanced or recurrent chronic lymphocytic leukemia (CLL), lymphoma, or multiple myeloma (MM).

SECONDARY OBJECTIVES:

I. To characterize the pharmacokinetics of AR-42 in this patient population. II. To analyze patient samples for descriptive information regarding AR-42 pharmacodynamic changes in this patient population.

III. To obtain pilot data regarding efficacy at the MTD as measured by partial and complete responses in each disease subgroup during protocol expansion in stage III.

OUTLINE:

Patients receive oral AR-42 three times weekly on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Inclusion Hematologic Malignances Arm

• Patients must have CLL, prolymphocytic leukemia, or lymphoma (Hodgkins or Non-Hodgkins) as defined by 2008 WHO criteria or multiple myeloma as defined by IMWG criteria
• Patients must have received at least one prior antineoplastic therapy, must have progressed after at least 1 prior therapy, and for whom no standard therapy is available or whom decline such options; prior autologous and/or allogeneic transplant is permitted
• Prior biologic therapy or prior radiation is permitted; however, at least 28 days must have elapsed since the completion of prior therapy and patients must have recovered from all therapy-associated toxicities to no greater than grade 1 at the time of registration
• Patients with symptomatic disease may receive palliative corticosteroids up to 1 week before initiating therapy
• Patients must be off any prior chemotherapy for at least 28 days or 3 half lives, whichever is longer, and all therapy-related toxicity must have resolved to grade 1 or less
• ANC >= 1000/uL
• Total bilirubin < 1.5 mg/dL
• Serum creatinine =< 1.5x institutional upper limit of normal or estimated creatinine clearance >= 50 ml/min by MDRD (original or abbreviated), or measured creatinine clearance >= 50 mL/min
• ECOG/WHO performance score of 0-1
• Patients must be able to swallow capsules
• Patients or their legal representatives must be able to read, understand and provide informed consent to participate in the trial
• Women with potential for child bearing must have a negative pregnancy test at screening; both men and women are required to use appropriate contraception during study
• Platelet count >= 50,000/uL
• AST and ALT =< 5x the institutional upper limit of normal Inclusion Solid Tumors Arm
• Histologically or cytologically confirmed advanced or recurrent solid tumor malignancy.
• Chemotherapy: up to three prior cytotoxic chemotherapy treatments.
• Radiation Therapy: prior radiation therapy allowed.
• Surgery: Prior curative and palliative intent surgery is allowed.
• Age ≥ 18 years
• ECOG performance status 0-1
• Life expectancy of greater than 12 weeks.
• Patients must have normal organ and marrow function as defined below:
• Leukocytes ≥ 3,000/mcL
• Absolute neutrophil count ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Total bilirubin < 1.5 mg/dL
• AST(SGOT)/ALT(SGPT) ≤ 2.5 x institutional upper limit of normal (ULN); ≤ 5 x ULN in presence of liver metastasis
• Creatinine ≤ 1.5 x ULN OR Creatinine clearance ≥ 50 mL/min by MDRD (original or abbreviated), or measured creatinine clearance ≥ 50 ml/min
• Patients or their legal representatives must be able to read, understand and provide informed consent to participate in the trial
• Women with potential for child bearing must have a negative pregnancy test at screening; both men and women are required to use appropriate contraception during study

Exclusion Hematologic Malignances Arm

• Pregnant women are excluded from this study
• Patients with malabsorption or any other condition that in the opinion of the principal investigator could cause difficulty in absorption of drug
• Breastfeeding should be discontinued if the mother is treated with AR-42
• Patients with malignant cells in the cerebrospinal fluid or parenchyma within the preceding 3 months or patients with primary CNS lymphoma are not eligible
• Patients with uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP) are not eligible
• Patients receiving concurrent corticosteroids less than 1 week prior to protocol therapy other than for physiologic maintenance treatment or control of AIHA or ITP
• Concurrent use of complementary or alternative medicines that in the opinion of the principal investigator would confound the interpretation of toxicities and/or antitumor activity of the study drug
• Patients with a "currently active" second malignancy that, in the opinion of the principal investigator, will interfere with patient participation, increase patient risk, shorten survival to < 1 year, or confound data interpretation
• Patients with a mean QTcB > 450 msec in males and > 470 msec in females
• Patients who are receiving concurrent antineoplastic therapy
• Any other medical condition, including mental illness or substance abuse, deemed by the principal investigator 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 results
• Patients with significant cardiovascular disease, including a myocardial infarction or unstable angina within 6 months or unstable cardiac arrhythmias are not eligible for the study
• Known HIV infection

Exclusion Solid Tumors Arm

• Pregnant women are excluded from this study
• Patients with malabsorption or any other condition that in the opinion of the principal investigator could cause difficulty in absorption of drug
• Patients with malignant cells in the cerebrospinal fluid or parenchyma within the preceding 3 months or patients with primary CNS lymphoma are not eligible
• Patients with uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP) are not eligible
• Patients receiving concurrent corticosteroids less than 1 week prior to protocol therapy other than for physiologic maintenance treatment or control of AIHA or ITP
• Concurrent use of complementary or alternative medicines that in the opinion of the principal investigator would confound the interpretation of toxicities and/or antitumor activity of the study drug
• Concurrent use of complementary or alternative medicines that in the opinion of the principal investigator would confound the interpretation of toxicities and/or antitumor activity of the study drug
• Patients with a "currently active" second malignancy that, in the opinion of the principal investigator, will interfere with patient participation, increase patient risk, shorten survival to < 1 year, or confound data interpretation.
• Patients with a mean QTcB > 450 msec in males and > 470 msec in females
• Patients who are receiving concurrent antineoplastic therapy.
• Any other medical condition, including mental illness or substance abuse, deemed by the principal investigator 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 results.
• Patients with significant cardiovascular disease, including a myocardial infarction or unstable angina within 6 months or unstable cardiac arrhythmias are not eligible for the study.