Safety Study of Darinaparsin in Combination With Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) to Treat Lymphoma
Primary Purpose
Lymphoma
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
darinaparsin
CHOP
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma focused on measuring Lymphoma, Darinaparsin, CHOP, Frontline, PTCL, B-cell
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single Arm, darinaparsin and CHOP
Arm Description
open label, single arm, unblinded
Outcomes
Primary Outcome Measures
Define Toxicity profile
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
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).
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01139359
Brief Title
Safety Study of Darinaparsin in Combination With Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) to Treat Lymphoma
Official Title
A Phase I Dose Escalation Study of Darinaparsin in Combination With CHOP in Previously Untreated Patients With Lymphomas Who Are Scheduled to Receive CHOP Alone
Study Type
Interventional
2. Study Status
Record Verification Date
July 2012
Overall Recruitment Status
Withdrawn
Why Stopped
Study enrollment was withdrawn as it is no longer the sponsor's intention to study this indication under this protocol.
Study Start Date
June 2010 (undefined)
Primary Completion Date
June 2011 (Anticipated)
Study Completion Date
June 2011 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alaunos Therapeutics
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
Lymphoma, Darinaparsin, CHOP, Frontline, PTCL, B-cell
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single Arm, darinaparsin and CHOP
Arm Type
Experimental
Arm Description
open label, single arm, unblinded
Intervention Type
Drug
Intervention Name(s)
darinaparsin
Other Intervention Name(s)
ZIO-101, Zinapar(TM)
Intervention Description
I.V. darinaparsin given in a dose escalation manner, once a day for 5 days per cycle.
Intervention Type
Drug
Intervention Name(s)
CHOP
Intervention Description
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.
Primary Outcome Measure Information:
Title
Define Toxicity profile
Description
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)
Time Frame
One Year
Title
Maximum Tolerated Dose
Description
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).
Time Frame
One Year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jonathan J. Lewis, MD, PhD
Organizational Affiliation
ZIOPHARM, Oncology, Inc.
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
Safety Study of Darinaparsin in Combination With Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) to Treat Lymphoma
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