Study of Volasertib and Belinostat in Patients With Relapsed and Refractory Aggressive B-cell and T-cell Lymphomas

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