Study of PNT2258 for Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma

Inclusion Criteria:

1. Written informed consent must be obtained from the patient.
2. Participants must be ≥18 years of age.
3. Morphologically confirmed diagnosis of non-Hodgkin's lymphoma (NHL).
4. At least a single measureable tumor mass (long axis \> 1.5 cm).
5. An FDG-PET positive baseline scan.

   a. A positive scan is defined per revised Cheson criteria as "focal or diffuse FDG uptake above background in a location incompatible with normal anatomy or physiology, without a specific standardized uptake value cutoff".
6. Disease that has relapsed after administration of primary therapy that included:

   1. Rituximab and
   2. CHOP, EPOCH, bendamustine or similar chemotherapy or subsequent salvage regimen.

   Note: Relapse is defined as progression after a complete response to therapy or radiographic evidence of active disease after a partial response or stable disease.
7. Have received three or fewer complete courses of systemic cytotoxic regimens. Note: Rituximab (alone or in combination with cytotoxic chemotherapy) is not considered a cytotoxic regimen.
8. No previous exposure to PNT2258.
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
10. Have discontinued all prior anti-cancer therapies for at least 21 days; biologic therapy for at least 4 half-lives of the drug(s); radio-immunotherapy (10 weeks); autologous stem cell transplantation (SCT) (3 months) and must be at a stable baseline regarding any acute toxicity associated with prior therapy.
11. Adequate organ function including:

    1. Hematologic Function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L prior to treatment. Platelets ≥ 100 x 109/L.
    2. Hepatic: Total Bilirubin ≤ 1.5 x ULN and serum transaminase levels ≤ 2.5 x upper limits of normal (ULN).
    3. Renal: Serum creatinine ≤2 x ULN or creatinine clearance ≥ 60 mL/min/1.73 m2 for subjects with serum creatinine levels above 2x ULN.

Exclusion Criteria:

1. Candidates for HDT and autologous SCT. Note: Patients who progressed \> 3 months after high-dose therapy (HDT)/SCT are eligible.
2. Concurrent malignancies requiring treatment.
3. Symptomatic central nervous system (CNS) or leptomeningeal involvement of lymphoma.
4. Concurrent serious medical conditions (as determined by the Principal Investigator) including, but not limited to, HIV-associated lymphoma; active bacterial, fungal or viral infections.
5. Signs and symptoms of heart failure characterized as greater than New York Heart Association (NYHA) Class I.
6. History of myocardial infarct or prolonged corrected QT (QTc) interval (\>450 milliseconds (msecs) for males or \>470 msecs for females) or other significant cardiac abnormalities.
7. Women who are pregnant or breast-feeding.