Trial Outcomes & Findings for Vorinostat, Cladribine, and Rituximab in Treating Patients With Mantle Cell Lymphoma, Relapsed Chronic Lymphocytic Leukemia, or Relapsed B Cell Non-Hodgkin's Lymphoma (NCT NCT00764517)

Last Updated: 2017-12-11

Results Overview

ORR defined as the percentage of patients who achieved a complete response (CR) or a partial response (PR). Assessed per the revised Cheson criteria. Response definitions per revised International Working Group Response Criteria. 95% confidence interval will be provided. Definitions: Complete response (CR) = disappearance of all evidence of disease; Partial response (PR) = regression of measurable disease and no new sites.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

57 participants

Primary outcome timeframe

2 years

Results posted on

2017-12-11

Participant Flow

Participant milestones

Participant milestones
Measure	Previously Untreated Patients enrolled with untreated, newly diagnosed mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL) \[Group I\]. Patients receive 400 mg vorinostat PO on days 1-14, 5 mg/m\^2 cladribine IV over 2 hours on days 1-5, and 375 mg/m\^2 rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	Relapsed Patients with relapsed disease including indolent Non-Hodgkins Lymphoma (NHL), mantle cell lymphoma (MCL), or chronic lymphocytic leukemia (CLL) \[Group II\]. Patients receive 400 mg vorinostat PO on days 1-14, 5 mg/m\^2 cladribine IV over 2 hours on days 1-5, and 375 mg/m\^2 rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	39	18
Overall Study COMPLETED	24	4
Overall Study NOT COMPLETED	15	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Previously Untreated Patients enrolled with untreated, newly diagnosed mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL) \[Group I\]. Patients receive 400 mg vorinostat PO on days 1-14, 5 mg/m\^2 cladribine IV over 2 hours on days 1-5, and 375 mg/m\^2 rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	Relapsed Patients with relapsed disease including indolent Non-Hodgkins Lymphoma (NHL), mantle cell lymphoma (MCL), or chronic lymphocytic leukemia (CLL) \[Group II\]. Patients receive 400 mg vorinostat PO on days 1-14, 5 mg/m\^2 cladribine IV over 2 hours on days 1-5, and 375 mg/m\^2 rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Overall Study Adverse Event	9	3
Overall Study Death	3	11
Overall Study Physician Decision	3	0

Baseline Characteristics

Vorinostat, Cladribine, and Rituximab in Treating Patients With Mantle Cell Lymphoma, Relapsed Chronic Lymphocytic Leukemia, or Relapsed B Cell Non-Hodgkin's Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Previously Untreated n=39 Participants Patients enrolled with untreated, newly diagnosed mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL) \[Group I\]. Patients receive 400 mg vorinostat PO on days 1-14, 5 mg/m\^2 cladribine IV over 2 hours on days 1-5, and 375 mg/m\^2 rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	Relapsed n=18 Participants Patients with relapsed disease including indolent Non-Hodgkins Lymphoma (NHL), mantle cell lymphoma (MCL), or chronic lymphocytic leukemia (CLL) \[Group II\]. Patients receive 400 mg vorinostat PO on days 1-14, 5 mg/m\^2 cladribine IV over 2 hours on days 1-5, and 375 mg/m\^2 rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	Total n=57 Participants Total of all reporting groups
Age, Continuous	62 years n=5 Participants	60 years n=7 Participants	61.5 years n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	34 Participants n=5 Participants	15 Participants n=7 Participants	49 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	37 Participants n=5 Participants	18 Participants n=7 Participants	55 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	37 Participants n=5 Participants	18 Participants n=7 Participants	55 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	39 Participants n=5 Participants	18 Participants n=7 Participants	57 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 years

Outcome measures

Outcome measures
Measure	Previously Untreated n=39 Participants Patients enrolled with untreated, newly diagnosed mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL) \[Group I\]. Patients receive 400 mg vorinostat PO on days 1-14, 5 mg/m\^2 cladribine IV over 2 hours on days 1-5, and 375 mg/m\^2 rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	Relapsed n=18 Participants Patients with relapsed disease including indolent Non-Hodgkins Lymphoma (NHL), mantle cell lymphoma (MCL), or chronic lymphocytic leukemia (CLL) \[Group II\]. Patients receive 400 mg vorinostat PO on days 1-14, 5 mg/m\^2 cladribine IV over 2 hours on days 1-5, and 375 mg/m\^2 rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Objective Response Rate	97 percentage of participants Interval 87.0 to 100.0	39 percentage of participants Interval 17.0 to 64.0

PRIMARY outcome

Timeframe: 6 months

Toxicity is determined percentage of patients that experienced an adverse event (AE) grade 3 or higher during the time frame, assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade refers to the severity of the AE increasing from Grade 1 to 5. Generally, Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe or medically significant but not immediately life-threatening; Grade 4 = Life-threatening consequences; Grade 5 = Death related to AE.

Outcome measures

Outcome measures
Measure	Previously Untreated n=39 Participants Patients enrolled with untreated, newly diagnosed mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL) \[Group I\]. Patients receive 400 mg vorinostat PO on days 1-14, 5 mg/m\^2 cladribine IV over 2 hours on days 1-5, and 375 mg/m\^2 rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	Relapsed n=18 Participants Patients with relapsed disease including indolent Non-Hodgkins Lymphoma (NHL), mantle cell lymphoma (MCL), or chronic lymphocytic leukemia (CLL) \[Group II\]. Patients receive 400 mg vorinostat PO on days 1-14, 5 mg/m\^2 cladribine IV over 2 hours on days 1-5, and 375 mg/m\^2 rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Toxicities as Assessed Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0	90 percentage of participants Interval 76.0 to 97.0	83 percentage of participants Interval 59.0 to 96.0

PRIMARY outcome

Timeframe: 6 months

Tolerability is determined to be the percentage of patients who completed the full duration of treatment (all 6 cycles) regardless of adverse event status. % tolerability shows the rate of patients that tolerated the treatment for the full duration.

Outcome measures

Outcome measures
Measure	Previously Untreated n=39 Participants Patients enrolled with untreated, newly diagnosed mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL) \[Group I\]. Patients receive 400 mg vorinostat PO on days 1-14, 5 mg/m\^2 cladribine IV over 2 hours on days 1-5, and 375 mg/m\^2 rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	Relapsed n=18 Participants Patients with relapsed disease including indolent Non-Hodgkins Lymphoma (NHL), mantle cell lymphoma (MCL), or chronic lymphocytic leukemia (CLL) \[Group II\]. Patients receive 400 mg vorinostat PO on days 1-14, 5 mg/m\^2 cladribine IV over 2 hours on days 1-5, and 375 mg/m\^2 rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Tolerability of Treatment	62 percentage of participants Interval 45.0 to 77.0	22 percentage of participants Interval 6.0 to 48.0

SECONDARY outcome

Timeframe: Up to 5 years

Time from treatment start until disease progression or death. Estimated using the Kaplan-Meier method. A logrank test will be used to compare progression-free survival between Group I and Group II. A p-value less that 0.05 will be considered statistically significant.

Outcome measures

Outcome measures
Measure	Previously Untreated n=39 Participants Patients enrolled with untreated, newly diagnosed mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL) \[Group I\]. Patients receive 400 mg vorinostat PO on days 1-14, 5 mg/m\^2 cladribine IV over 2 hours on days 1-5, and 375 mg/m\^2 rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	Relapsed n=18 Participants Patients with relapsed disease including indolent Non-Hodgkins Lymphoma (NHL), mantle cell lymphoma (MCL), or chronic lymphocytic leukemia (CLL) \[Group II\]. Patients receive 400 mg vorinostat PO on days 1-14, 5 mg/m\^2 cladribine IV over 2 hours on days 1-5, and 375 mg/m\^2 rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Progression-free Survival	NA Months Interval 25.0 to Median survival not reached. Upper confidence limit is inestimable.	19.5 Months Interval 2.0 to 33.0

SECONDARY outcome

Timeframe: Up to 5 years

Time from treatment start until disease progression, death, or discontinuation of treatment for adverse event (toxicity) Estimated using the Kaplan-Meier method. A logrank test will be used to compare progression-free survival between Group I and Group II. A p-value less that 0.05 will be considered statistically significant.

Outcome measures

Outcome measures
Measure	Previously Untreated n=39 Participants Patients enrolled with untreated, newly diagnosed mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL) \[Group I\]. Patients receive 400 mg vorinostat PO on days 1-14, 5 mg/m\^2 cladribine IV over 2 hours on days 1-5, and 375 mg/m\^2 rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	Relapsed n=18 Participants Patients with relapsed disease including indolent Non-Hodgkins Lymphoma (NHL), mantle cell lymphoma (MCL), or chronic lymphocytic leukemia (CLL) \[Group II\]. Patients receive 400 mg vorinostat PO on days 1-14, 5 mg/m\^2 cladribine IV over 2 hours on days 1-5, and 375 mg/m\^2 rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Event-free Survival	39.0 Months Interval 25.0 to Upper confidence limit is inestimatable	19.5 Months Interval 2.0 to 34.0

SECONDARY outcome

Timeframe: Up to 2 years

Population: Data not collected and the outcome will never be analyzed.

Determine the contribution (if any) of DNA methylation/histone deacetylation to disease progression and/or response to SCR combination chemotherapy. Outcome not evaluated due to technical challenges collecting the data, and lack of budget and personnel to complete the analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline

Population: Data not collected and the outcome will never be analyzed.

Perform scientific correlates to determine if SCR treatment a) is associated with global and gene specific changes in transcription of mRNAs and MiRNAs b) is acting as an inhibitor of DNA methylation c) is activating or silencing specific genes or miRNAs. Outcome not evaluated due to technical challenges collecting the data, and lack of budget and personnel to complete the analysis.

Outcome measures

Outcome data not reported

Adverse Events

Previously Untreated

Serious events: 18 serious events

Other events: 28 other events

Deaths: 8 deaths

Relapsed

Serious events: 9 serious events

Other events: 14 other events

Deaths: 13 deaths

Serious adverse events

Serious adverse events
Measure	Previously Untreated n=39 participants at risk Patients enrolled with untreated, newly diagnosed mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL) \[Group I\]. Patients receive 400 mg vorinostat PO on days 1-14, 5 mg/m\^2 cladribine IV over 2 hours on days 1-5, and 375 mg/m\^2 rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	Relapsed n=18 participants at risk Patients with relapsed disease including indolent Non-Hodgkins Lymphoma (NHL), mantle cell lymphoma (MCL), or chronic lymphocytic leukemia (CLL) \[Group II\]. Patients receive 400 mg vorinostat PO on days 1-14, 5 mg/m\^2 cladribine IV over 2 hours on days 1-5, and 375 mg/m\^2 rituximab IV on day 3 (weekly for the first course). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Investigations Alanine aminotransferase increased	2.6% 1/39 • Number of events 1 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)	0.00% 0/18 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)
Immune system disorders Allergic reaction	2.6% 1/39 • Number of events 1 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)	0.00% 0/18 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)
Blood and lymphatic system disorders Anemia	2.6% 1/39 • Number of events 1 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)	5.6% 1/18 • Number of events 1 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)
Investigations Aspartate aminotransferase increased	2.6% 1/39 • Number of events 1 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)	0.00% 0/18 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)
Investigations Cardiac troponin I increased	2.6% 1/39 • Number of events 1 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)	0.00% 0/18 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)
General disorders Death NOS	0.00% 0/39 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)	5.6% 1/18 • Number of events 1 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)
Blood and lymphatic system disorders Febrile neutropenia	10.3% 4/39 • Number of events 4 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)	5.6% 1/18 • Number of events 1 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)
Metabolism and nutrition disorders Hyperglycemia	2.6% 1/39 • Number of events 1 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)	0.00% 0/18 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)
Metabolism and nutrition disorders Hypokalemia	2.6% 1/39 • Number of events 1 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)	0.00% 0/18 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)
Investigations INR increased	2.6% 1/39 • Number of events 1 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)	0.00% 0/18 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)
Investigations Neutrophil count decreased	23.1% 9/39 • Number of events 10 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)	22.2% 4/18 • Number of events 4 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)
Investigations Platelet count decreased	10.3% 4/39 • Number of events 4 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)	22.2% 4/18 • Number of events 4 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)
Respiratory, thoracic and mediastinal disorders Pulmonary edema	2.6% 1/39 • Number of events 1 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)	0.00% 0/18 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/39 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)	5.6% 1/18 • Number of events 1 • Up to 25 weeks (6 cycles X 28 days + 1 week after last cycle. Toxicities and adverse experiences will be assessed at each visit using the NCI Common Terminology Criteria for Adverse Events v4.0. Adverse events evaluated and recorded using the NCI CTCAE, Version 4.0 for 1 week after last cycle. For reporting purposes here, Grade 4 will be considered to be serious adverse event (SAE). Events assessed at each visit during the study (every other week for Cycle 1, then monthly for Cycles 2 to 6)

Other adverse events

Additional Information

Dr. Stephen E. Spurgeon MD

Knight Cancer Institute, Oregon Health & Science University

Phone: 503-494-4606

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place