This phase 1, multicenter, open-label study is designed to find the RP2D of volasertib, a PLK1 inhibitor, and belinostat, an HDAC inhibitor, when given in combination to patients with relapsed or refractory B-cell or T-cell lymphoma. A standard 3+3 dose-escalation design will be employed with study enrollment beginning at dose level 1.

Inclusion Criteria:

A patient must meet all of the following inclusion criteria to be eligible to participate in the study.

• Histologically confirmed aggressive B-cell or T-cell lymphoma including the following:
• B-cell lymphomas
• DLBCL (including transformed follicular lymphoma)
• Mantle cell lymphoma
• Burkitt lymphoma
• Peripheral T-cell lymphoma (PTCL) excluding cutaneous T-cell lymphoma
• Disease that is relapsed or refractory after a minimum of 2 previous therapies, if B-cell lymphoma, or a minimum of 1 previous therapy, if PTCL
• For patients who have had autologous stem cell transplant, disease relapse must be more than 100 days following transplant.
• For patients who have had allogeneic stem cell transplant, all of the following conditions must be met:
• ≥ 6 months since allogeneic transplant
• Graft vs. host disease (GVHD) is not present
• Patient is not currently on immunosuppressive therapy
• At least one site of measurable disease by PET/CT: a node measurable in 2 diameters and with longest diameter >1.5cm or an extranodal lesion measurable in 2 diameters and with longest diameter >1cm.
• Age ≥ 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (see Appendix 1)
• Life expectancy of at least 3 months
• CBC with differential providing evidence of adequate bone marrow function as defined below:
• Absolute neutrophil count (ANC) ≥ 1500/mm3 without growth factor support for 7 days
• Platelets ≥ 75,000/mm3 (without transfusion for 7 days)
• Adequate renal function defined as: Creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated or actual creatinine clearance ≥ 60 mL/min (see Appendix 2 for the Cockcroft -Gault Formula to calculate creatinine clearance)
• Adequate hepatic function as defined below:
• AST ≤ 2.5 x ULN
• ALT ≤ 2.5 x ULN
• Total bilirubin ≤ 1.5 mg/dL
• Note: Patients with documented Gilbert's syndrome are eligible if total bilirubin is ≤ 3.0 mg/dL.
• Serum potassium and serum magnesium within normal limits Note: Electrolytes may be corrected with supplementation.
• For a woman of childbearing potential (WCBP), a negative serum pregnancy test performed within 14 days prior to study enrollment (7 days prior to initiation of study treatment) Note: WCBP is defined as any woman who has not had a hysterectomy or bilateral oophorectomy and is not postmenopausal (i.e., she has had menses in the preceding 24 consecutive months)
• WCBP and male patients must agree to use a highly effective method of birth control for the duration of study treatment and for 6 months following completion of study treatment Note: A highly effective method of contraception is defined as one that results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomised partner.
• Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

A patient who meets any of the following exclusion criteria is ineligible to participate in the study.

• Any investigational treatment within 30 days prior to initiation of study treatment
• Plans for concurrent treatment with other investigational agents
• Plans for other concurrent cancer treatment including steroids for cancer control
• Chemotherapy or large field radiotherapy within 3 weeks prior to initiation of study treatment
• Previous histone deacetylase inhibitor administered as cancer treatment.
• History of brain metastasis including leptomeningeal metastasis
• QTc interval ≥450 (i.e., ≥ grade 0, per CTCAE version 4) on ECG prior to initiation of study treatment. If baseline QTc on screening ECG is ≥ 450 ms (i.e., ≥ grade 1)
• Check potassium and magnesium serum levels
• Correct any identified hypokalemia and/or hypomagnesemia and repeat ECG to confirm QTc interval
• For patients with baseline HR < 60 or > 100 bpm, manual read of QT by cardiologist is required, with Fridericia correction applied to determine the QTcF interval.
• Note: For patients with HR 60-100 bpm, no manual read of QTc is required.
• Any of the following related to risk of torsades de pointes and sudden cardiac death:
• History of sustained ventricular tachycardia (VT, ventricular fibrillation (VF), torsades de pointes, or resuscitated cardiac arrest unless currently addressed with an implanted cardiac defibrillator
• Concomitant treatment with an anti-arrhythmic agent to prevent or control arrhythmia. Agents used for rate-control of atrial fibrillation are permitted provide that they are not prohibited due to potential drug interactions (see Section 6.4)
• Known congenital long QT syndrome
• Second degree atrioventricular (AV) block type II, third degree AV block, or ventricular rate < 50 bpm
• Any of the following related to ischemic heart disease:
• Angina with ordinary physical activity
• Note: If angina only occurs with strenuous, rapid, or prolonged exertion, the patient is eligible.
• Myocardial infarction within 6 months prior to study enrollment
• Note: If myocardial infarction occurred within 6-12 months prior to study enrollment, patient must be asymptomatic and have had a negative cardiac risk assessment (e.g., treadmill stress test, nuclear medicine stress test, or stress echocardiogram)
• ECG with evidence of cardiac ischemia (i.e., ST depression of ≥ 2 mm, measured from isoelectric line to ST segment; T-wave inversion ≥ 4 mm measured from isoelectric line to peak of T-wave)
• Any of the following related to heart failure:
• New York Heart Association (NYHA) class II, III or IV congestive heart failure (see Appendix 3) or known left ventricular ejection fraction < 40% by MUGA scan or < 50% by echocardiogram or MRI
• Known hypertrophic cardiomegaly or restrictive cardiomyopathy
• Clinically significant infection including active hepatitis B or hepatitis C requiring treatment
• Known human immunodeficiency virus (HIV) seropositivity nNote: HIV testing is not required
• History of allergic reactions attributed to compounds similar to the chemical or biologic composition of belinostat or volasertib
• History of another primary malignancy, excluding non-melanoma skin cancer, cervical carcinoma in situ, and/or other in situ cancers treated by local excision, that has not been in remission for at least 2 years
• Pregnancy or breastfeeding
• Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk, interfere with the patient's participation in the study, or hinder evaluation of study results