Trial Outcomes & Findings for S0106 Cytarabine and Daunorubicin w/ or w/o Gemtuzumab Followed By HD Cytarabine and Either Gemtuzumab or Nothing in de Novo AML (NCT NCT00085709)

Last Updated: 2015-09-30

Results Overview

Measured from data of randomization to post-consolidation therapy until relapse from complete response or death from any cause, with observations censored at the date of last contact for patients last known to be alive without report of relapse.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

637 participants

Primary outcome timeframe

After completing any treatment, every 6 months for 2 years, than annually for years 3-5

Results posted on

2015-09-30

Participant Flow

Participant milestones

Participant milestones
Measure	Ara-C+Daunomycin+Mylotarg Gemtuzumab (GO) added to the standard induction regimen of 7 days of Ara-C (cytosine arabinoside)and 3 days of daunomycin	ARA-C+Daunomycin Standard induction regimen of 7 days of Ara-C (cytosine arabinoside)and 3 days of daunomycin
Overall Study STARTED	317	320
Overall Study Eligible	298	301
Overall Study Eligible and Did Not Withdraw Consent	296	300
Overall Study COMPLETED	264	270
Overall Study NOT COMPLETED	53	50

Reasons for withdrawal

Reasons for withdrawal
Measure	Ara-C+Daunomycin+Mylotarg Gemtuzumab (GO) added to the standard induction regimen of 7 days of Ara-C (cytosine arabinoside)and 3 days of daunomycin	ARA-C+Daunomycin Standard induction regimen of 7 days of Ara-C (cytosine arabinoside)and 3 days of daunomycin
Overall Study Adverse Event	8	0
Overall Study Death	8	2
Overall Study Refusal unrelated to adverse events	1	2
Overall Study Progression	3	4
Overall Study Not protocol specified	12	22
Overall Study Not eligible	19	19
Overall Study Withdrawal by Subject	2	1

Baseline Characteristics

S0106 Cytarabine and Daunorubicin w/ or w/o Gemtuzumab Followed By HD Cytarabine and Either Gemtuzumab or Nothing in de Novo AML

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ara-C+Daunomycin+Mylotarg n=296 Participants Ara-C+Daunomycin+Mylotarg	ARA-C+Daunomycin n=300 Participants ARA-C+Daunomycin	Total n=596 Participants Total of all reporting groups
Age, Continuous	47 years n=5 Participants	48 years n=7 Participants	47 years n=5 Participants
Sex: Female, Male Female	135 Participants n=5 Participants	148 Participants n=7 Participants	283 Participants n=5 Participants
Sex: Female, Male Male	161 Participants n=5 Participants	152 Participants n=7 Participants	313 Participants n=5 Participants

PRIMARY outcome

Timeframe: After completing any treatment, every 6 months for 2 years, than annually for years 3-5

Population: Eligible patients who completed induction and consolidation therapy

Outcome measures

Outcome measures
Measure	Post-consolidation GO n=84 Participants For patients who remain in CR without relapse, patients may receive up to 3 doses of G.O. 28 days apart.	Post-consolidation Observation n=84 Participants Patients did not receive any post-consolidation therapy	Ara-C Consolidation For patients who achieved a CR during induction, patients may receive up to 3 28 day cycles of treatment with Ara-C consolidation. Patients who relapse from CR are taken off protocol consolidation treatment.	Post-consolidation G.O. For patients who remain in CR without relapse, patients may receive up to 3 doses of G.O. 28 days apart.
2-year Disease-free Survival (DFS)	39 Percentage of population Interval 27.0 to 51.0	50 Percentage of population Interval 38.0 to 62.0	—	—

PRIMARY outcome

Timeframe: After induction therapy was completed (1 or 2 months)

Population: Eligible patients who did not withdraw consent

Outcome measures

Outcome measures
Measure	Post-consolidation GO n=296 Participants For patients who remain in CR without relapse, patients may receive up to 3 doses of G.O. 28 days apart.	Post-consolidation Observation n=300 Participants Patients did not receive any post-consolidation therapy	Ara-C Consolidation For patients who achieved a CR during induction, patients may receive up to 3 28 day cycles of treatment with Ara-C consolidation. Patients who relapse from CR are taken off protocol consolidation treatment.	Post-consolidation G.O. For patients who remain in CR without relapse, patients may receive up to 3 doses of G.O. 28 days apart.
Complete Remission	203 participants	207 participants	—	—

SECONDARY outcome

Timeframe: For induction, daily for the first 10 days, then twice weekly until consolidation treatment. Weekly during consolidation treatment. Weekly if randomized to post-consolidation G.O.

Population: Eligible patients who started therapy

Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event

Outcome measures

Adverse Events

Induction 7 + 3 + G.O.

Serious events: 47 serious events

Other events: 277 other events

Deaths: 0 deaths

Induction 7 + 3

Serious events: 9 serious events

Other events: 279 other events

Deaths: 0 deaths

Ara-C Consolidation

Serious events: 13 serious events

Other events: 356 other events

Deaths: 0 deaths

Post-consolidation G.O.

Serious events: 19 serious events

Other events: 77 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

SWOG Leukemia Statistician

SWOG Statistical Office

Phone: 206-667-4408

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Induction 7 + 3 + G.O. n=293 participants at risk A 21 day treatment cycle of Induction 7+3+G.O. with a 2nd 21 day cycle of the same for patients who did not achieve a complete remission (CR) during the first cycle of treatment	Induction 7 + 3 n=293 participants at risk A 21 day treatment cycle of Induction 7+3 with a 2nd 21 day cycle of the same for patients who did not achieve a complete remission during the first cycle of treatment	Ara-C Consolidation n=375 participants at risk For patients who achieved a CR during induction, patients may receive up to 3 28 day cycles of treatment with Ara-C consolidation. Patients who relapse from CR are taken off protocol consolidation treatment.	Post-consolidation G.O. n=78 participants at risk For patients who remain in CR without relapse, patients may receive up to 3 doses of G.O. 28 days apart.
Infections and infestations Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Skin (celluli	0.34% 1/293 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	1.3% 1/78 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Infections and infestations Infection-Other (Specify)	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	1.3% 1/78 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Investigations ALT, SGPT (serum glutamic pyruvic transaminase)	1.7% 5/293 • Number of events 5 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.27% 1/375 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	1.3% 1/78 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Investigations AST, SGOT (serum glutamic oxaloacetic transaminase)	1.4% 4/293 • Number of events 4 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.27% 1/375 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	1.3% 1/78 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Blood and lymphatic system disorders DIC (disseminated intravascular coagulation)	0.34% 1/293 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Blood and lymphatic system disorders Febrile neutropenia	2.4% 7/293 • Number of events 7 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.34% 1/293 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	1.1% 4/375 • Number of events 4 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	11.5% 9/78 • Number of events 9 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Blood and lymphatic system disorders Hemoglobin	0.34% 1/293 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Cardiac disorders Cardiac-ischemia/infarction	0.34% 1/293 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Cardiac disorders Pericardial effusion (non-malignant)	0.34% 1/293 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Cardiac disorders Pericarditis	0.34% 1/293 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Gastrointestinal disorders Colitis	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.34% 1/293 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Gastrointestinal disorders Mucositis/stomatitis (clinical exam) - Oral cavity	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	1.3% 1/78 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Gastrointestinal disorders Nausea	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	1.3% 1/78 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Gastrointestinal disorders Pain - Rectum	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	1.3% 1/78 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Gastrointestinal disorders Perforation, GI - Colon	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.34% 1/293 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Gastrointestinal disorders Typhlitis (cecal inflammation)	0.34% 1/293 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.34% 1/293 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Gastrointestinal disorders Vomiting	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	1.3% 1/78 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
General disorders Death not associated with CTCAE term - Multi-organ failure	0.34% 1/293 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
General disorders Fatigue (asthenia, lethargy, malaise)	0.34% 1/293 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
General disorders Syndromes-Other (Specify)	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.27% 1/375 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Hepatobiliary disorders Hepatobiliary/Pancreas-Other (Specify)	0.34% 1/293 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Hepatobiliary disorders Liver dysfunction/failure (clinical)	1.4% 4/293 • Number of events 4 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Hepatobiliary disorders Portal vein flow	0.34% 1/293 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Immune system disorders Allergic reaction/hypersensitivity (including drug fever)	0.68% 2/293 • Number of events 2 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Infections and infestations Colitis, infectious (e.g., Clostridium difficile)	0.34% 1/293 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Infections and infestations Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Blood	2.7% 8/293 • Number of events 8 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.68% 2/293 • Number of events 2 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.27% 1/375 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	3.8% 3/78 • Number of events 3 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Infections and infestations Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Colon	0.34% 1/293 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Infections and infestations Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Heart (endoca	0.34% 1/293 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Infections and infestations Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Lung (pneumon	1.0% 3/293 • Number of events 3 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.34% 1/293 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.27% 1/375 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Infections and infestations Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Pelvis NOS	0.34% 1/293 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Investigations Alkaline phosphatase	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.27% 1/375 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Investigations Bilirubin (hyperbilirubinemia)	1.0% 3/293 • Number of events 3 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Investigations Creatinine	0.34% 1/293 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Investigations Leukocytes (total WBC)	1.7% 5/293 • Number of events 5 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.27% 1/375 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	2.6% 2/78 • Number of events 2 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Investigations Metabolic/Laboratory-Other (Specify)	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.27% 1/375 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Investigations Neutrophils/granulocytes (ANC/AGC)	1.0% 3/293 • Number of events 3 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.27% 1/375 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	6.4% 5/78 • Number of events 5 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Investigations Platelets	3.1% 9/293 • Number of events 9 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.34% 1/293 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.27% 1/375 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	2.6% 2/78 • Number of events 2 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Metabolism and nutrition disorders Calcium, serum-low (hypocalcemia)	1.0% 3/293 • Number of events 3 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Metabolism and nutrition disorders Dehydration	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	1.3% 1/78 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	1.3% 1/78 • Number of events 1 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.

Other adverse events
Measure	Induction 7 + 3 + G.O. n=293 participants at risk A 21 day treatment cycle of Induction 7+3+G.O. with a 2nd 21 day cycle of the same for patients who did not achieve a complete remission (CR) during the first cycle of treatment	Induction 7 + 3 n=293 participants at risk A 21 day treatment cycle of Induction 7+3 with a 2nd 21 day cycle of the same for patients who did not achieve a complete remission during the first cycle of treatment	Ara-C Consolidation n=375 participants at risk For patients who achieved a CR during induction, patients may receive up to 3 28 day cycles of treatment with Ara-C consolidation. Patients who relapse from CR are taken off protocol consolidation treatment.	Post-consolidation G.O. n=78 participants at risk For patients who remain in CR without relapse, patients may receive up to 3 doses of G.O. 28 days apart.
Blood and lymphatic system disorders Febrile neutropenia	58.7% 172/293 • Number of events 172 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	66.2% 194/293 • Number of events 194 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	47.5% 178/375 • Number of events 178 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	17.9% 14/78 • Number of events 14 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Blood and lymphatic system disorders Hemoglobin	39.6% 116/293 • Number of events 116 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	37.2% 109/293 • Number of events 109 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	53.6% 201/375 • Number of events 201 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	34.6% 27/78 • Number of events 27 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Eye disorders Vision-blurred vision	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	5.1% 19/375 • Number of events 19 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Gastrointestinal disorders Constipation	12.3% 36/293 • Number of events 36 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	10.9% 32/293 • Number of events 32 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	12.3% 46/375 • Number of events 46 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	6.4% 5/78 • Number of events 5 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Gastrointestinal disorders Diarrhea	39.2% 115/293 • Number of events 115 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	44.4% 130/293 • Number of events 130 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	20.3% 76/375 • Number of events 76 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	11.5% 9/78 • Number of events 9 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Gastrointestinal disorders Heartburn/dyspepsia	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	8.5% 25/293 • Number of events 25 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	5.3% 20/375 • Number of events 20 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Gastrointestinal disorders Hemorrhage, GI - Oral cavity	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	5.1% 19/375 • Number of events 19 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Gastrointestinal disorders Mucositis/stomatitis (clinical exam) - Oral cavity	25.9% 76/293 • Number of events 76 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	21.8% 64/293 • Number of events 64 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	16.8% 63/375 • Number of events 63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	10.3% 8/78 • Number of events 8 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Gastrointestinal disorders Mucositis/stomatitis (functional/symptomatic) - Oral cavity	11.3% 33/293 • Number of events 33 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	12.6% 37/293 • Number of events 37 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	9.3% 35/375 • Number of events 35 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Gastrointestinal disorders Nausea	56.3% 165/293 • Number of events 165 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	54.3% 159/293 • Number of events 159 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	48.5% 182/375 • Number of events 182 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	51.3% 40/78 • Number of events 40 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Gastrointestinal disorders Pain - Abdomen NOS	17.4% 51/293 • Number of events 51 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	11.9% 35/293 • Number of events 35 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	8.3% 31/375 • Number of events 31 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	10.3% 8/78 • Number of events 8 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Gastrointestinal disorders Vomiting	31.7% 93/293 • Number of events 93 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	25.6% 75/293 • Number of events 75 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	25.9% 97/375 • Number of events 97 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	28.2% 22/78 • Number of events 22 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
General disorders Edema: limb	13.0% 38/293 • Number of events 38 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	8.2% 24/293 • Number of events 24 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	7.2% 27/375 • Number of events 27 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
General disorders Fatigue (asthenia, lethargy, malaise)	47.8% 140/293 • Number of events 140 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	48.5% 142/293 • Number of events 142 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	56.0% 210/375 • Number of events 210 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	52.6% 41/78 • Number of events 41 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
General disorders Fever (in the absence of neutropenia, where neutropenia is defined as ANC lt1.0 x 10e9/L)	19.1% 56/293 • Number of events 56 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	18.8% 55/293 • Number of events 55 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	25.9% 97/375 • Number of events 97 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	17.9% 14/78 • Number of events 14 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
General disorders Rigors/chills	24.2% 71/293 • Number of events 71 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	18.8% 55/293 • Number of events 55 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	14.9% 56/375 • Number of events 56 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	10.3% 8/78 • Number of events 8 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Immune system disorders Allergic reaction/hypersensitivity (including drug fever)	5.1% 15/293 • Number of events 15 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Infections and infestations Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Blood	7.8% 23/293 • Number of events 23 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	8.2% 24/293 • Number of events 24 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	12.5% 47/375 • Number of events 47 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Infections and infestations Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Lung (pneumon	7.5% 22/293 • Number of events 22 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	8.9% 26/293 • Number of events 26 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	6.1% 23/375 • Number of events 23 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Investigations ALT, SGPT (serum glutamic pyruvic transaminase)	42.3% 124/293 • Number of events 124 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	30.7% 90/293 • Number of events 90 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	36.5% 137/375 • Number of events 137 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	43.6% 34/78 • Number of events 34 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Investigations AST, SGOT (serum glutamic oxaloacetic transaminase)	43.0% 126/293 • Number of events 126 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	31.4% 92/293 • Number of events 92 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	32.3% 121/375 • Number of events 121 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	42.3% 33/78 • Number of events 33 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Investigations Alkaline phosphatase	27.0% 79/293 • Number of events 79 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	20.5% 60/293 • Number of events 60 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	22.4% 84/375 • Number of events 84 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	28.2% 22/78 • Number of events 22 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Investigations Bilirubin (hyperbilirubinemia)	17.4% 51/293 • Number of events 51 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	21.5% 63/293 • Number of events 63 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	20.0% 75/375 • Number of events 75 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Investigations Creatinine	11.6% 34/293 • Number of events 34 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	6.5% 19/293 • Number of events 19 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	6.1% 23/375 • Number of events 23 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Investigations Leukocytes (total WBC)	34.5% 101/293 • Number of events 101 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	33.1% 97/293 • Number of events 97 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	40.5% 152/375 • Number of events 152 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	51.3% 40/78 • Number of events 40 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Investigations Lymphopenia	10.9% 32/293 • Number of events 32 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	9.2% 27/293 • Number of events 27 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	13.3% 50/375 • Number of events 50 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	12.8% 10/78 • Number of events 10 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Investigations Metabolic/Laboratory-Other (Specify)	5.5% 16/293 • Number of events 16 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	5.6% 21/375 • Number of events 21 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Investigations Neutrophils/granulocytes (ANC/AGC)	37.2% 109/293 • Number of events 109 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	37.9% 111/293 • Number of events 111 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	52.0% 195/375 • Number of events 195 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	51.3% 40/78 • Number of events 40 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Investigations Platelets	46.4% 136/293 • Number of events 136 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	44.4% 130/293 • Number of events 130 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	60.5% 227/375 • Number of events 227 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	62.8% 49/78 • Number of events 49 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Metabolism and nutrition disorders Albumin, serum-low (hypoalbuminemia)	23.5% 69/293 • Number of events 69 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	18.1% 53/293 • Number of events 53 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	21.6% 81/375 • Number of events 81 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	7.7% 6/78 • Number of events 6 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Metabolism and nutrition disorders Anorexia	29.0% 85/293 • Number of events 85 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	25.6% 75/293 • Number of events 75 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	20.3% 76/375 • Number of events 76 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	11.5% 9/78 • Number of events 9 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Metabolism and nutrition disorders Calcium, serum-low (hypocalcemia)	15.0% 44/293 • Number of events 44 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	18.1% 53/293 • Number of events 53 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	11.7% 44/375 • Number of events 44 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	6.4% 5/78 • Number of events 5 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	27.0% 79/293 • Number of events 79 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	24.2% 71/293 • Number of events 71 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	25.9% 97/375 • Number of events 97 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	26.9% 21/78 • Number of events 21 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Metabolism and nutrition disorders Magnesium, serum-low (hypomagnesemia)	5.8% 17/293 • Number of events 17 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	6.7% 25/375 • Number of events 25 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Metabolism and nutrition disorders Phosphate, serum-low (hypophosphatemia)	5.8% 17/293 • Number of events 17 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	6.1% 18/293 • Number of events 18 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Metabolism and nutrition disorders Potassium, serum-high (hyperkalemia)	6.8% 20/293 • Number of events 20 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Metabolism and nutrition disorders Potassium, serum-low (hypokalemia)	18.8% 55/293 • Number of events 55 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	15.0% 44/293 • Number of events 44 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	16.3% 61/375 • Number of events 61 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	15.4% 12/78 • Number of events 12 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Metabolism and nutrition disorders Sodium, serum-low (hyponatremia)	14.3% 42/293 • Number of events 42 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	14.0% 41/293 • Number of events 41 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	10.4% 39/375 • Number of events 39 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	10.3% 8/78 • Number of events 8 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Metabolism and nutrition disorders Uric acid, serum-high (hyperuricemia)	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	5.3% 20/375 • Number of events 20 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/78 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy) - Whole body/generalized	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/293 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	0.00% 0/375 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.	5.1% 4/78 • Number of events 4 • While the patient is on treatment until resolution of acute toxicities with maximum grade reported. Regular investigator assessments are reported after each cycle of protocol treatment.