Safety Study of Darinaparsin in Combination With Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) to Treat Lymphoma

• Define Toxicity profile [ Time Frame: One Year ] [ Designated as safety issue: Yes ]
  This is an open-label, dose-escalation Phase I study to define the toxicity profile and the maximum tolerated dose (MTD) of intravenously administered darinaparsin in combination with CHOP in patients with previously untreated lymphomas who are scheduled to receive CHOP alone (rituximab is not permitted)
• Maximum Tolerated Dose [ Time Frame: One Year ] [ Designated as safety issue: Yes ]
  This is an open-label, dose-escalation Phase I study to define the toxicity profile and the maximum tolerated dose (MTD) of intravenously administered darinaparsin in combination with CHOP in patients with previously untreated lymphomas who are scheduled to receive CHOP alone (rituximab is not permitted).

This study is a Phase I trial of Darinaparsin in combination with CHOP for the treatment of lymphoma. Eligible patients will not have had any previous anti-cancer treatment and will be eligible to receive CHOP alone.

• Drug: darinaparsin
  I.V. darinaparsin given in a dose escalation manner, once a day for 5 days per cycle.
  Other Names:

  • ZIO-101
  • Zinapar(TM)
• Drug: CHOP
  Cyclophosphamide 750 mg/m2 IV Day 8 of each Cycle; Doxorubicin 50 mg/m2 IV Day 8 of each Cycle; Vincristine 1.4 mg/m2 IV Day 8 of each Cycle; Prednisone 100 mg oral Days 8-12 of each Cycle.

Inclusion Criteria:

• Patients with histological or cytological confirmation of lymphoma who are previously untreated and are scheduled to receive CHOP alone. Since the objective of the study is the assessment of safety, eligible subjects may have any type of lymphoma (Hodgkin's or non-Hodgkin's, T-cell or B-cell), as long as the scheduled therapy is CHOP alone.
• Men and women of ≥18 years of age.
• ECOG performance score ≤2
• Life expectancy ≥12 weeks.

• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements, to be conducted <2 weeks prior to first dose of study drug:

  • Creatinine ≤1.5 × upper limit of normal (ULN) OR a calculated creatinine clearance ≥60 cc/min
  • Total bilirubin ≤2 × ULN
  • Alanine transaminase (ALT) and aspartate transaminase (AST) ≤3 × ULN
  • Granulocytes in peripheral blood ≥1 × 109/L, hemoglobin ≥10 g/dL, and platelets ≥50,000 /µL
• Adequate vascular access for repeated blood sampling.
• Men and women of childbearing potential must agree to use effective contraception from Screening through 30 days after the last dose of study drug.
• Written informed consent in compliance with ZIOPHARM policies and the Human Investigation Review Committee (IEC/IRB) having jurisdiction over the site.

Exclusion Criteria:

• Arsenic allergy.
• New York Heart Association (NYHA) functional class ≥3 myocardial infarction (see Appendix 3) within 6 months.
• Myocardial dysfunction defined as scintigraphically- (MUGA [multiple gated acquisition scan], myocardial scintigram) or ultrasound-determined left ventricular ejection fraction (LVEF) <50%.
• Uncontrolled cardiac arrhythmia other than asymptomatic atrial fibrillation; a QTc ≥450 msec; or a ≥Grade 2 atrioventricular (AV) block or left bundle branch block (LBBB); or documented history of prolonged QTc.
• Pregnant and/or lactating women.
• Uncontrolled systemic infection (documented with microbiological studies).
• Metastatic brain or meningeal tumors. -Patients with seizure disorder requiring medication (such as anti- branch block (LBBB); or documented history of prolonged QTc.
• History of confusion or dementia or neurological condition that could mask a potential adverse response to the Study Drug, which may include transient ischemic attack, Parkinson's disease, thrombotic or hemorrhagic stroke, Alzheimer's, and other neurological disorders.
• Anticancer chemotherapy or immunotherapy for this indication.
• Radiotherapy during study or within 3 weeks of Study entry.
• Major surgery within 4 weeks of start of Study Drug dosing.
• Investigational drug therapy outside of this trial.
• History of invasive second primary malignancy diagnosed within the previous 3 years except for Stage I endometrial/cervical carcinoma or prostate carcinoma treated surgically, and non-melanoma skin cancer.
• Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of Study results.
• Any condition that is unstable or could jeopardize the safety of the patient and his/her compliance in the Study.