Trial Outcomes & Findings for Pixantrone Dimaleate in Treating Patients With HER2-Negative Metastatic Breast Cancer (NCT NCT01086605)

Last Updated: 2018-05-08

Results Overview

The proportion of confirmed responses will be estimated by the number of women who achieve a CR or PR on two consecutive evaluations at least 6-8 weeks apart depending on the dose level. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients at each dose level. Confidence intervals for the true success proportion at each dose level will be calculated according to the approach of Duffy and Santner. Response will be evaluated in this study using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1); Complete Response (CR): Disappearance of all non-nodal target lesions, each target lymph node must have reduction in short axis to \<1.0 cm. and normalization of tumor biomarkers. Partial Response (PR): At least a 30% decrease in the sum of the longest diameters of the non-nodal target lesions and the short axis of the target lymph nodes taking as reference the Baseline Sum of Diameters.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

46 participants

Primary outcome timeframe

Up to 5 years

Results posted on

2018-05-08

Participant Flow

Participant milestones

Participant milestones
Measure	Arm I/Group A (Pixantrone IV Day 1) Patients receive 180 mg/m\^2 pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Arm II/Group B (Pixantrone IV Days 1, 8, and 15) Patients receive 85 mg/m\^2 pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	24	22
Overall Study COMPLETED	24	22
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pixantrone Dimaleate in Treating Patients With HER2-Negative Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I/Group A (Pixantrone IV Day 1) n=24 Participants Patients receive 180 mg/m\^2 pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Arm II/Group B (Pixantrone IV Days 1, 8, and 15) n=22 Participants Patients receive 85 mg/m\^2 pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Total n=46 Participants Total of all reporting groups
Age, Continuous	56.5 years n=5 Participants	52.5 years n=7 Participants	55.5 years n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	22 Participants n=7 Participants	45 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	24 participants n=5 Participants	22 participants n=7 Participants	46 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 5 years

Outcome measures

Outcome measures
Measure	Arm I/Group A (Pixantrone IV Day 1) n=24 Participants Patients receive 180 mg/m\^2 pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Arm II/Group B (Pixantrone IV Days 1, 8, and 15) n=22 Participants Patients receive 85 mg/m\^2 pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Proportion of Confirmed Tumor Responses (Complete or Partial Response)	0.08 proportion Interval 0.01 to 0.27	0.05 proportion Interval 0.0 to 0.24

SECONDARY outcome

Timeframe: Up to 5 years

Time to disease progression is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had disease progression at the time of their death. If the patient is declared to be a major treatment violation, the patient will be censored on the date the treatment violation was declared to have occurred. In the case of a patient starting treatment and then never returning for any evaluations, the patient will be censored for progression one day post-registration. The distribution of time to progression will be estimated using the method of Kaplan-Meier at each dose level. Progression is defined using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1).

Outcome measures

Outcome measures
Measure	Arm I/Group A (Pixantrone IV Day 1) n=24 Participants Patients receive 180 mg/m\^2 pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Arm II/Group B (Pixantrone IV Days 1, 8, and 15) n=22 Participants Patients receive 85 mg/m\^2 pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Time to Disease Progression	2.8 months Interval 1.4 to 7.9	2.5 months Interval 1.7 to 4.1

SECONDARY outcome

Timeframe: At 6 months

The 6-month progression free survival (6-mo PFS) rate is the proportion of efficacy-evaluable patients progression-free 6 months from registration. The 6-mo PFS rate is defined as the total number of efficacy-evaluable patients on study without documentation of disease progression 6 months from registration divided by the total number of efficacy-evaluable patients enrolled on study. Patients who died without documentation of progression will be considered to have progressed on the date of their death. The true 6-mo PFS rate will be estimated by the proportion of efficacy-evaluable patients on study without documentation of disease progression 6 months from registration at each dose level. Binomial confidence intervals for 6-mo PFS rate will be constructed for each dose level. Progression is defined using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1).

Outcome measures

Outcome measures
Measure	Arm I/Group A (Pixantrone IV Day 1) n=24 Participants Patients receive 180 mg/m\^2 pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Arm II/Group B (Pixantrone IV Days 1, 8, and 15) n=22 Participants Patients receive 85 mg/m\^2 pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
6-month Progression-free Survival Rate	0.375 proportion Interval 0.224 to 0.629	0.265 proportion Interval 0.227 to 0.553

SECONDARY outcome

Timeframe: Up to 5 years

Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier at each dose level.

Outcome measures

Outcome measures
Measure	Arm I/Group A (Pixantrone IV Day 1) n=24 Participants Patients receive 180 mg/m\^2 pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Arm II/Group B (Pixantrone IV Days 1, 8, and 15) n=22 Participants Patients receive 85 mg/m\^2 pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Overall Survival Time	16.8 months Interval 9.0 to The study did not have enough deaths or patients were not followed long enough to get the upper limit of the 95% confidence interval of median overall survival.	9.6 months Interval 4.7 to The study did not have enough deaths or patients were not followed long enough to get the upper limit of the 95% confidence interval of median overall survival.

SECONDARY outcome

Timeframe: Up to 5 years

Duration of response is defined for all evaluable patients with measurable disease who have achieved a confirmed response as the date at which the patient's earliest best objective status is first noted to be either a CR or PR to the earliest date progression is documented at each dose level. If a patient dies subsequent to the confirmed response without a documentation of disease progression, the patient will be considered to have had disease progression at the time of their death. In the case of a patient failing to return for evaluations before a documentation of disease progression, the patient will be censored for progression on the date of last evaluation. The distribution of duration of response will be estimated using the method of Kaplan-Meier at each dose level.

Outcome measures

Outcome measures
Measure	Arm I/Group A (Pixantrone IV Day 1) n=46 Participants Patients receive 180 mg/m\^2 pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Arm II/Group B (Pixantrone IV Days 1, 8, and 15) Patients receive 85 mg/m\^2 pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Duration of Response	5.8 months Interval 4.6 to 7.2	—

SECONDARY outcome

Timeframe: Up to 1 year after treatment

For this secondary endpoint, toxicity is defined as a grade 3 or higher adverse events that is classified as either possibly, probably, or definitely related to study treatment. The assignment of attribution to study treatment and grade (or degree of severity) of the adverse event are classified using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The number of participants reporting a grade 3 or higher toxicity is reported. For a list of all reported adverse events, please refer to the Adverse Events Section below.

Outcome measures

Outcome measures
Measure	Arm I/Group A (Pixantrone IV Day 1) n=24 Participants Patients receive 180 mg/m\^2 pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Arm II/Group B (Pixantrone IV Days 1, 8, and 15) n=21 Participants Patients receive 85 mg/m\^2 pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Toxicity	16 Participants	19 Participants

Adverse Events

Arm I/Group A

Serious events: 3 serious events

Other events: 23 other events

Deaths: 0 deaths

Arm II/Group B

Serious events: 9 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Alvaro Moreno-Asptia, M.D.

Mayo Clinic

Phone: 507/284-1159

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Arm I/Group A n=24 participants at risk Patients receive 180 mg/m\^2 pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Arm II/Group B n=22 participants at risk Patients receive 85 mg/m\^2 pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
General disorders Death NOS	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
General disorders Edema limbs	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
General disorders Fatigue	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Hepatobiliary disorders Hepatic failure	4.2% 1/24 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	0.00% 0/22 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Alanine aminotransferase increased	4.2% 1/24 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	0.00% 0/22 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Aspartate aminotransferase increased	4.2% 1/24 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Blood bilirubin increased	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Ejection fraction decreased	4.2% 1/24 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Lymphocyte count decreased	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Neutrophil count decreased	8.3% 2/24 • Number of events 2 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	9.1% 2/22 • Number of events 3 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations White blood cell decreased	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	9.1% 2/22 • Number of events 2 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	9.1% 2/22 • Number of events 2 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Vascular disorders Thromboembolic event	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.

Other adverse events
Measure	Arm I/Group A n=24 participants at risk Patients receive 180 mg/m\^2 pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Arm II/Group B n=22 participants at risk Patients receive 85 mg/m\^2 pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	75.0% 18/24 • Number of events 62 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	81.8% 18/22 • Number of events 43 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Cardiac disorders Sinus tachycardia	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Ear and labyrinth disorders Ear pain	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Ear and labyrinth disorders Hearing impaired	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Eye disorders Watering eyes	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	9.1% 2/22 • Number of events 7 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Gastrointestinal disorders Abdominal pain	4.2% 1/24 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	0.00% 0/22 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Gastrointestinal disorders Constipation	16.7% 4/24 • Number of events 7 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	13.6% 3/22 • Number of events 4 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Gastrointestinal disorders Diarrhea	41.7% 10/24 • Number of events 17 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	27.3% 6/22 • Number of events 7 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Gastrointestinal disorders Hemorrhoids	4.2% 1/24 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	0.00% 0/22 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Gastrointestinal disorders Mucositis oral	33.3% 8/24 • Number of events 17 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Gastrointestinal disorders Nausea	66.7% 16/24 • Number of events 54 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	72.7% 16/22 • Number of events 25 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Gastrointestinal disorders Oral pain	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Gastrointestinal disorders Periodontal disease	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 3 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Gastrointestinal disorders Vomiting	37.5% 9/24 • Number of events 12 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	40.9% 9/22 • Number of events 12 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
General disorders Chills	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
General disorders Edema limbs	4.2% 1/24 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
General disorders Fatigue	87.5% 21/24 • Number of events 76 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	90.9% 20/22 • Number of events 49 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
General disorders Fever	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	9.1% 2/22 • Number of events 2 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
General disorders Flu like symptoms	4.2% 1/24 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	0.00% 0/22 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
General disorders General disorders and administration site conditions - Other, specify	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 4 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
General disorders Malaise	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
General disorders Pain	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	9.1% 2/22 • Number of events 2 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Hepatobiliary disorders Hepatobiliary disorders - Other, specify	4.2% 1/24 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	0.00% 0/22 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Immune system disorders Allergic reaction	4.2% 1/24 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	0.00% 0/22 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Infections and infestations Bronchial infection	4.2% 1/24 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	0.00% 0/22 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Infections and infestations Lung infection	4.2% 1/24 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	0.00% 0/22 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Infections and infestations Upper respiratory infection	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Infections and infestations Urinary tract infection	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Activated partial thromboplastin time prolonged	4.2% 1/24 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	0.00% 0/22 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Alanine aminotransferase increased	16.7% 4/24 • Number of events 6 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	27.3% 6/22 • Number of events 8 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Alkaline phosphatase increased	4.2% 1/24 • Number of events 1 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	22.7% 5/22 • Number of events 5 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Aspartate aminotransferase increased	20.8% 5/24 • Number of events 10 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	36.4% 8/22 • Number of events 14 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Blood bilirubin increased	8.3% 2/24 • Number of events 2 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	18.2% 4/22 • Number of events 4 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Creatinine increased	8.3% 2/24 • Number of events 9 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	9.1% 2/22 • Number of events 3 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Ejection fraction decreased	12.5% 3/24 • Number of events 3 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	4.5% 1/22 • Number of events 3 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Lymphocyte count decreased	8.3% 2/24 • Number of events 5 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	18.2% 4/22 • Number of events 5 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Neutrophil count decreased	83.3% 20/24 • Number of events 40 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	95.5% 21/22 • Number of events 54 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Platelet count decreased	20.8% 5/24 • Number of events 10 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	36.4% 8/22 • Number of events 10 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Investigations Weight loss	0.00% 0/24 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.	9.1% 2/22 • Number of events 5 • Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year). The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.