Trial Outcomes & Findings for Oxaliplatin, Fludarabine, Cytarabine, and Rituximab in Patients With Richter's Transformation and Leukemias (NCT NCT00472849)

Last Updated: 2013-11-26

Results Overview

Maximum dose levels for Phase I determined among three possible dose levels of Fludarabine and Cytarabine in combination with fixed doses of Oxaliplatin and Rituximab. Fludarabine and Cytarabine Dose Level 1: Days 2-3 (2 Days); Dose Level 2: Days 2-4 (3 Days); and Dose 3: Days 2-5 (4 Days). MTD is dose level at which less than 2/3 or 2/6 participants experience dose limiting toxicities (DLTs). The number of days of fludarabine and cytarabine administration increased simultaneously. Participants received a subsequent cycle of treatment with 1 additional day of fludarabine and cytarabine treatment no less than 4 weeks from the initiation of the previous cycle if no drug-related grade 3 or 4 non-hematologic life-threatening adverse events, and drug-related non-hematologic toxicity resolved to baseline or \< grade 2. A maximum of 6 cycles were administered.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

92 participants

Primary outcome timeframe

Up to 36 weeks (6 cycles each 4-6 weeks)

Results posted on

2013-11-26

Participant Flow

Recruitment Period 5/31/2007- 2/1/2012; All participants were registered at The University of Texas MD Anderson Cancer Center.

Of the 92 participants enrolled on this study, two participants were excluded as having failed screening and never received study medication.

Participant milestones

Participant milestones
Measure	OFAR (Phase I) Oxaliplatin starting dose 30 mg/m\^2/day over 2 hours on days 1-4 before Fludarabine. Fludarabine 30 mg/m\^2 daily intravenous (IV) over 30 minutes on days 2-3, 2-4, or 2-5 until maximum tolerated dose reached. Cytarabine 500 mg/m\^2 daily IV, 2-hour infusion starting 4 hours after first fludarabine dose started, on days 2-3, 2-4, or 2-5, until maximum tolerated dose reached. Rituximab 375 mg/m\^2 IV on day 3, course 1 (on day 1, subsequent courses). Pegfilgrastim 6 mg subcutaneously once per chemotherapy cycle, approximately 24 hours after last dose of chemotherapy.	OFAR (Phase II) Oxaliplatin 25 mg/m\^2 IV per day (Phase I MTD) on days 1-4 before Fludarabine. Fludarabine 30 mg/m\^2 daily IV over 30 minutes on days 2-4. Cytarabine 500 mg/m\^2 daily IV, 2-hour infusion starting 4 hours after fludarabine dose started, on days 2-4. Rituximab 375 mg/m\^2 IV on day 3, course 1 (on day 1, subsequent courses). Pegfilgrastim 6 mg subcutaneously once per chemotherapy cycle, approximately 24 hours after last dose of chemotherapy.
Overall Study STARTED	12	78
Overall Study COMPLETED	12	78
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Oxaliplatin, Fludarabine, Cytarabine, and Rituximab in Patients With Richter's Transformation and Leukemias

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OFAR (Phase I) n=12 Participants Oxaliplatin 30 mg/m\^2/day over 2 hours before on days 1-4 Fludarabine. Fludarabine 30 mg/m\^2 daily IV over 30 minutes on days 2-3, 2-4, or 2-5 until maximum tolerated dose reached. Cytarabine 500 mg/m\^2 daily IV, 2-hour infusion starting 4 hours after first fludarabine dose started, on days 2-3, 2-4, or 2-5, until maximum tolerated dose reached. Rituximab 375 mg/m\^2 IV on day 3, course 1 (on day 1, subsequent courses).	OFAR MTD (Phase II) n=78 Participants Oxaliplatin 25 mg/m\^2 IV per day MTD on days 1-4 before Fludarabine. Fludarabine 30 mg/m\^2 daily IV over 30 minutes on days 2-4. Cytarabine 500 mg/m\^2 daily IV, 2-hour infusion starting 4 hours after fludarabine dose started, on days 2-4. Rituximab 375 mg/m\^2 IV on day 3, course 1 (on day 1, subsequent courses). Pegfilgrastim 6 mg subcutaneously once per chemotherapy cycle, approximately 24 hours after last dose of chemotherapy.	Total n=90 Participants Total of all reporting groups
Age Continuous	65 Years n=5 Participants	63 Years n=7 Participants	63 Years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	20 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	58 Participants n=7 Participants	67 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants	78 participants n=7 Participants	90 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 36 weeks (6 cycles each 4-6 weeks)

Outcome measures

Outcome measures
Measure	OFAR MTD (Phase II) n=12 Participants Oxaliplatin 25 mg/m\^2 IV per day MTD on days 1-4 before Fludarabine. Fludarabine 30 mg/m\^2 daily IV over 30 minutes on days 2-4. Cytarabine 500 mg/m\^2 daily IV, 2-hour infusion starting 4 hours after fludarabine dose started, on days 2-4. Rituximab 375 mg/m\^2 IV on day 3, course 1 (on day 1, subsequent courses). Pegfilgrastim 6 mg subcutaneously once per chemotherapy cycle, approximately 24 hours after last dose of chemotherapy.
Maximum Total Tolerated Dose (MTD) of Daily Combination Fludarabine 30 mg/m^2 and Cytarabine 500 mg/m^2 Among 3 Dose Levels (Dose Level 1: 2 Days, Dose Level 2: 3 Days or Dose Level 3: 4 Days) Fludarabine MTD (Total 3 Day Dose)	90 mg/m^2
Maximum Total Tolerated Dose (MTD) of Daily Combination Fludarabine 30 mg/m^2 and Cytarabine 500 mg/m^2 Among 3 Dose Levels (Dose Level 1: 2 Days, Dose Level 2: 3 Days or Dose Level 3: 4 Days) Cytarabine MTD (Total 3 Day Dose)	1500 mg/m^2

SECONDARY outcome

Timeframe: Up to 36 weeks (6 cycles each 4-6 weeks)

Overall Response includes Complete remission (CR), nodular partial remission (nPR), and partial remission (PR) in high-risk, previously untreated participants with Chronic Lymphocytic Leukemia treated with CFAR using National Cancer Institute - Working Group response criteria. CR defined as zero nodes, Liver/spleen not palpable, zero symptoms, polymorphonuclear leukocyte (PMN)\>1,500/uL, Platelets \>100,000uL, Hemoglobin (untransfused) \>11.0g/dL, Lymphocytes \<4,000/uL and Bone Marrow Aspirate biopsy \<30% lymphocytes with no lymphocyte infiltrate; PR defined as nodes \>/= 50% decrease,Liver/spleen \>/= 50% decrease, symptoms not applicable, PMN \>1,500/uL or \>50% improvement from baseline, Platelets 100,000uL or \>/=50% decrease improvement from baseline, Hemoglobin (untransfused) \>11.0g/dL or \>50% improvement from baseline, Lymphocytes \>50% decrease and Bone Marrow Aspirate biopsy Not Applicable for PR; with nPR defined same as PR but with \<30% lymphocytes with residual disease on biopsy.

Outcome measures

Outcome measures
Measure	OFAR MTD (Phase II) n=78 Participants Oxaliplatin 25 mg/m\^2 IV per day MTD on days 1-4 before Fludarabine. Fludarabine 30 mg/m\^2 daily IV over 30 minutes on days 2-4. Cytarabine 500 mg/m\^2 daily IV, 2-hour infusion starting 4 hours after fludarabine dose started, on days 2-4. Rituximab 375 mg/m\^2 IV on day 3, course 1 (on day 1, subsequent courses). Pegfilgrastim 6 mg subcutaneously once per chemotherapy cycle, approximately 24 hours after last dose of chemotherapy.
Overall Response: Number of Participants With Complete Remission, Nodular Partial Remission, and Partial Remission Complete Remission	3 participants
Overall Response: Number of Participants With Complete Remission, Nodular Partial Remission, and Partial Remission Partial Remission	27 participants
Overall Response: Number of Participants With Complete Remission, Nodular Partial Remission, and Partial Remission Nodular Partial Remission	9 participants

Adverse Events

OFAR (Phase I)

Serious events: 8 serious events

Other events: 8 other events

Deaths: 0 deaths

OFAR MTD (Phase II)

Serious events: 15 serious events

Other events: 71 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

William G. Wierda, MD, PhD, BS / Associate Professor

The University of Texas MD Anderson Cancer Center

Phone: 713-745-0428

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	OFAR (Phase I) n=12 participants at risk Oxaliplatin 30 mg/m\^2/day over 2 hours before on days 1-4 Fludarabine. Fludarabine 30 mg/m\^2 daily IV over 30 minutes on days 2-3, 2-4, or 2-5 until maximum tolerated dose reached. Cytarabine 500 mg/m\^2 daily IV, 2-hour infusion starting 4 hours after first fludarabine dose started, on days 2-3, 2-4, or 2-5, until maximum tolerated dose reached. Rituximab 375 mg/m\^2 IV on day 3, course 1 (on day 1, subsequent courses).	OFAR MTD (Phase II) n=78 participants at risk Oxaliplatin 25 mg/m\^2 IV per day MTD on days 1-4 before Fludarabine. Fludarabine 30 mg/m\^2 daily IV over 30 minutes on days 2-4. Cytarabine 500 mg/m\^2 daily IV, 2-hour infusion starting 4 hours after fludarabine dose started, on days 2-4. Rituximab 375 mg/m\^2 IV on day 3, course 1 (on day 1, subsequent courses). Pegfilgrastim 6 mg subcutaneously once per chemotherapy cycle, approximately 24 hours after last dose of chemotherapy.
Renal and urinary disorders Renal Failure	0.00% 0/12 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	1.3% 1/78 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Gastrointestinal disorders Nausea/Vomiting	0.00% 0/12 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	1.3% 1/78 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Gastrointestinal disorders Abdominal Pain	0.00% 0/12 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	1.3% 1/78 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Gastrointestinal disorders Dehydration	8.3% 1/12 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	3.8% 3/78 • Number of events 3 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Gastrointestinal disorders Diarrhea	16.7% 2/12 • Number of events 2 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	1.3% 1/78 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
General disorders Death	8.3% 1/12 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	6.4% 5/78 • Number of events 5 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Infections and infestations Infection	16.7% 2/12 • Number of events 2 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	3.8% 3/78 • Number of events 3 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Blood and lymphatic system disorders Hemolysis	0.00% 0/12 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	1.3% 1/78 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
General disorders Dyspnea	8.3% 1/12 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	1.3% 1/78 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Secondary Malignancy	0.00% 0/12 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	2.6% 2/78 • Number of events 2 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Blood and lymphatic system disorders Hemorrhage	0.00% 0/12 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	1.3% 1/78 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Infections and infestations Neutropenic Fever	25.0% 3/12 • Number of events 3 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	0.00% 0/78 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Metabolism and nutrition disorders Hyponatremia	8.3% 1/12 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	0.00% 0/78 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	8.3% 1/12 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	0.00% 0/78 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Blood and lymphatic system disorders Immune Hemolytic Anemia	8.3% 1/12 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	0.00% 0/78 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Cardiac disorders Hypotension	0.00% 0/12 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	1.3% 1/78 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.

Measure	OFAR (Phase I) n=12 participants at risk Oxaliplatin 30 mg/m\^2/day over 2 hours before on days 1-4 Fludarabine. Fludarabine 30 mg/m\^2 daily IV over 30 minutes on days 2-3, 2-4, or 2-5 until maximum tolerated dose reached. Cytarabine 500 mg/m\^2 daily IV, 2-hour infusion starting 4 hours after first fludarabine dose started, on days 2-3, 2-4, or 2-5, until maximum tolerated dose reached. Rituximab 375 mg/m\^2 IV on day 3, course 1 (on day 1, subsequent courses).	OFAR MTD (Phase II) n=78 participants at risk Oxaliplatin 25 mg/m\^2 IV per day MTD on days 1-4 before Fludarabine. Fludarabine 30 mg/m\^2 daily IV over 30 minutes on days 2-4. Cytarabine 500 mg/m\^2 daily IV, 2-hour infusion starting 4 hours after fludarabine dose started, on days 2-4. Rituximab 375 mg/m\^2 IV on day 3, course 1 (on day 1, subsequent courses). Pegfilgrastim 6 mg subcutaneously once per chemotherapy cycle, approximately 24 hours after last dose of chemotherapy.
Gastrointestinal disorders Constipation	16.7% 2/12 • Number of events 2 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	5.1% 4/78 • Number of events 4 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Respiratory, thoracic and mediastinal disorders Hiccups	8.3% 1/12 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	5.1% 4/78 • Number of events 4 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Blood and lymphatic system disorders Edema	0.00% 0/12 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	5.1% 4/78 • Number of events 4 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Gastrointestinal disorders Anorexia	16.7% 2/12 • Number of events 2 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	5.1% 4/78 • Number of events 4 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
General disorders Pain	8.3% 1/12 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	5.1% 4/78 • Number of events 4 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Nervous system disorders Neuropathy	25.0% 3/12 • Number of events 3 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	6.4% 5/78 • Number of events 5 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Gastrointestinal disorders Mucositis	16.7% 2/12 • Number of events 2 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	6.4% 5/78 • Number of events 5 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Gastrointestinal disorders Dehydration	8.3% 1/12 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	6.4% 5/78 • Number of events 5 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Respiratory, thoracic and mediastinal disorders Cough	8.3% 1/12 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	7.7% 6/78 • Number of events 6 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Respiratory, thoracic and mediastinal disorders Shortness of Breath	0.00% 0/12 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	11.5% 9/78 • Number of events 9 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
General disorders Fever	0.00% 0/12 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	12.8% 10/78 • Number of events 10 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Gastrointestinal disorders Diarrhea	16.7% 2/12 • Number of events 2 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	15.4% 12/78 • Number of events 12 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Gastrointestinal disorders Nausea/Vomiting	25.0% 3/12 • Number of events 3 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	17.9% 14/78 • Number of events 14 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
General disorders Fatigue	16.7% 2/12 • Number of events 2 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	24.4% 19/78 • Number of events 19 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Infections and infestations Infection	0.00% 0/12 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	29.5% 23/78 • Number of events 27 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Blood and lymphatic system disorders Anemia	33.3% 4/12 • Number of events 4 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	44.9% 35/78 • Number of events 35 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Blood and lymphatic system disorders Neutropenia	66.7% 8/12 • Number of events 8 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	73.1% 57/78 • Number of events 57 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Blood and lymphatic system disorders Thrombocytopenia	50.0% 6/12 • Number of events 6 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	74.4% 58/78 • Number of events 58 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
General disorders Insomnia	8.3% 1/12 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	0.00% 0/78 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Skin and subcutaneous tissue disorders Rash	16.7% 2/12 • Number of events 2 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	0.00% 0/78 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
General disorders Hoarsness	8.3% 1/12 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	0.00% 0/78 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Nervous system disorders Anxiety	8.3% 1/12 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	0.00% 0/78 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Blood and lymphatic system disorders Nose Bleed	8.3% 1/12 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	0.00% 0/78 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
General disorders Weakness	8.3% 1/12 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	0.00% 0/78 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
General disorders Headache	8.3% 1/12 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	0.00% 0/78 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Blood and lymphatic system disorders Lymphopenia	8.3% 1/12 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	0.00% 0/78 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.
Musculoskeletal and connective tissue disorders Arthralgia	8.3% 1/12 • Number of events 1 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.	0.00% 0/78 • Adverse event collection from Day 1 of first cycle of therapy through sixth cycle then follow-up (every three to six months following first year) until off study. Enrollment started May 2007 and completion including follow up was January 2011.