Trial Outcomes & Findings for Chemoimmunotherapy With Epratuzumab in Relapsed Acute Lymphoblastic Leukemia (ALL) (NCT NCT00098839)

Last Updated: 2017-12-12

Results Overview

The proportion of patients who achieved complete response at the end Block 1 of re-induction therapy. Complete Remission (CR) - Attainment of M1 bone marrow (\<5% blasts) with no evidence of circulating blasts or extramedullary disease and with recovery of peripheral counts (ANC \>1000/uL and platelet count \>100,000/uL). Partial Remission (PR) - Complete disappearance of circulating blasts and achievement of M2 marrow status (5% or \< 25% blast cells and adequate cellularity). Partial Remission Cytolytic (PRCL) - Complete disappearance of circulating blasts and achievement of at least 50% reduction from baseline in bone marrow blast count. Minimal Response Cytolytic (MRCL) - 50% reduction in the peripheral blast count with no increase in peripheral white blood cell count.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

134 participants

Primary outcome timeframe

At the end of Block 1 of re-induction therapy (day 36)

Results posted on

2017-12-12

Participant Flow

The phase I part of the study was completed as of August 2006. The study was amended on 11/10/2006 and Part B (phase 2 pilot) was opened on 01/08/2007 which consisted of two dosing schedules for epratuzumab: weekly for four doses during Block 1 and twice weekly for eight doses during Block 1. This report is limited to Part B (116 enrollments).

Participant milestones

Participant milestones
Measure	Reinduction Chemoimmunotherapy With Epratuzumab Once Weekly Four weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 8, 15, 22. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, high-dose (HD) methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), Intrathecal triple therapy (ITT) (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC	Reinduction Chemoimmunotherapy With Epratuzumab Twice Weekly Eight 8 twice-weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 4, 8, 11, 15, 18, 22 \& 25. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, high-dose (HD) methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), Intrathecal triple therapy (ITT) (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC
Overall Study STARTED	56	60
Overall Study COMPLETED	24	27
Overall Study NOT COMPLETED	32	33

Reasons for withdrawal

Reasons for withdrawal
Measure	Reinduction Chemoimmunotherapy With Epratuzumab Once Weekly Four weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 8, 15, 22. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, high-dose (HD) methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), Intrathecal triple therapy (ITT) (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC	Reinduction Chemoimmunotherapy With Epratuzumab Twice Weekly Eight 8 twice-weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 4, 8, 11, 15, 18, 22 \& 25. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, high-dose (HD) methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), Intrathecal triple therapy (ITT) (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC
Overall Study Adverse Event	5	2
Overall Study Death	1	2
Overall Study Physician Decision	4	14
Overall Study Withdrawal by Subject	1	0
Overall Study Refusal of further protocol therapy	3	1
Overall Study Relapse	6	3
Overall Study M2/M3 marrow on Day 15 of Block 2	10	11
Overall Study Ineligible	2	0

Baseline Characteristics

Chemoimmunotherapy With Epratuzumab in Relapsed Acute Lymphoblastic Leukemia (ALL)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Reinduction Chemoimmunotherapy With Epratuzumab Once Weekly n=54 Participants Four weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 8, 15, 22. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, HD methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), ITT (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC	Reinduction Chemoimmunotherapy With Epratuzumab Twice Weekly n=60 Participants Eight 8 twice-weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 4, 8, 11, 15, 18, 22 \& 25. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, HD methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), ITT (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC	Total n=114 Participants Total of all reporting groups
Age, Continuous	10.5 years STANDARD_DEVIATION 5.54 • n=5 Participants	9.7 years STANDARD_DEVIATION 5.44 • n=7 Participants	10.1 years STANDARD_DEVIATION 5.48 • n=5 Participants
Age, Categorical <=18 years	48 Participants n=5 Participants	55 Participants n=7 Participants	103 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	29 Participants n=7 Participants	52 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants	31 Participants n=7 Participants	62 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) White	38 Participants n=5 Participants	46 Participants n=7 Participants	84 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	14 Participants n=5 Participants	20 Participants n=7 Participants	34 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	37 Participants n=5 Participants	38 Participants n=7 Participants	75 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: At the end of Block 1 of re-induction therapy (day 36)

Population: Evaluable patients at the end of Block 1. There were 2 ineligible patients for once weekly arm and 6 patients not evaluable at the end of block 1 re-induction therapy. There were 10 patients for twice weekly arm not evaluable at the end of block 1 re-induction therapy.

Outcome measures

Outcome measures
Measure	Reinduction Chemoimmunotherapy With Epratuzumab Once Weekly n=48 Participants Four weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 8, 15, 22. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, HD methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), ITT (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC	Reinduction Chemoimmunotherapy With Epratuzumab Twice Weekly n=50 Participants Eight 8 twice-weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 4, 8, 11, 15, 18, 22 \& 25. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, HD methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), ITT (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC
Remission Re-induction (CR2) Rate	.646 proportion of participants	.660 proportion of participants

PRIMARY outcome

Timeframe: At 4 months after enrollment

Proportion of patients who were event free at 4 months

Outcome measures

Outcome measures
Measure	Reinduction Chemoimmunotherapy With Epratuzumab Once Weekly n=48 Participants Four weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 8, 15, 22. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, HD methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), ITT (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC	Reinduction Chemoimmunotherapy With Epratuzumab Twice Weekly n=50 Participants Eight 8 twice-weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 4, 8, 11, 15, 18, 22 \& 25. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, HD methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), ITT (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC
Event-free Survival Rate	.604 Proportion of participants	.640 Proportion of participants

PRIMARY outcome

Timeframe: At the end of Block 1 of re-induction therapy (day 36)

Population: Evaluable patients who had MRD measured at the end of Block 1. There were 2 ineligible patients for once weekly arm and 13 patients where MRD was not measured at the end of block 1 re-induction therapy. There were 16 patients for twice weekly arm where MRD was not measured at the end of block 1 re-induction therapy.

Proportion of patients (evaluable and had MRD measured at the end of Block 1) who had MRD \< 0.01%.

Outcome measures

Outcome measures
Measure	Reinduction Chemoimmunotherapy With Epratuzumab Once Weekly n=41 Participants Four weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 8, 15, 22. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, HD methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), ITT (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC	Reinduction Chemoimmunotherapy With Epratuzumab Twice Weekly n=44 Participants Eight 8 twice-weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 4, 8, 11, 15, 18, 22 \& 25. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, HD methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), ITT (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC
Rate of Minimal Residual Disease (MRD) < 0.01%	.195 Proportion of participants	.295 Proportion of participants

SECONDARY outcome

Timeframe: Up to day 36

Population: Pharmacokinetics (PK) were added to the protocol with amendment 5A for the twice weekly dosing schedule of Epratuzumab. Hence, PK studies were limited to evaluable patients on this Arm only.

Mean trough serum concentration measured before final dose of epratuzumab.

Outcome measures

Outcome measures
Measure	Reinduction Chemoimmunotherapy With Epratuzumab Once Weekly n=26 Participants Four weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 8, 15, 22. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, HD methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), ITT (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC	Reinduction Chemoimmunotherapy With Epratuzumab Twice Weekly Eight 8 twice-weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 4, 8, 11, 15, 18, 22 \& 25. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, HD methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), ITT (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC
Pharmacokinetics	501 ug/mL Standard Deviation 149	—

Adverse Events

Reinduction Chemoimmunotherapy With Epratuzumab Once Weekly

Serious events: 16 serious events

Other events: 44 other events

Deaths: 0 deaths

Reinduction Chemoimmunotherapy With Epratuzumab Twice Weekly

Serious events: 20 serious events

Other events: 41 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Results Reporting Coordinator

Children's Oncology Group

Phone: 626-447-0064

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Must obtain prior Sponsor approval.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Reinduction Chemoimmunotherapy With Epratuzumab Once Weekly n=54 participants at risk Four weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 8, 15, 22. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, HD methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), ITT (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC	Reinduction Chemoimmunotherapy With Epratuzumab Twice Weekly n=60 participants at risk Eight 8 twice-weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 4, 8, 11, 15, 18, 22 \& 25. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, HD methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), ITT (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC
Blood and lymphatic system disorders Anemia	7.4% 4/54 • Number of events 4 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Blood and lymphatic system disorders Disseminated intravascular coagulation	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Blood and lymphatic system disorders Febrile neutropenia	9.3% 5/54 • Number of events 5 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	18.3% 11/60 • Number of events 11 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Cardiac disorders Cardiac arrest	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	0.00% 0/60 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Cardiac disorders Cardiac disorders - Other	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	0.00% 0/60 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Cardiac disorders Conduction disorder	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Cardiac disorders Sinus bradycardia	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	5.0% 3/60 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Cardiac disorders Sinus tachycardia	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Cardiac disorders Ventricular arrhythmia	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Gastrointestinal disorders Abdominal pain	3.7% 2/54 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	6.7% 4/60 • Number of events 4 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Gastrointestinal disorders Colitis	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Gastrointestinal disorders Colonic fistula	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Gastrointestinal disorders Colonic perforation	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Gastrointestinal disorders Constipation	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Gastrointestinal disorders Diarrhea	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Gastrointestinal disorders Enterocolitis	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Gastrointestinal disorders Gastroparesis	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Gastrointestinal disorders Mucositis oral	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Gastrointestinal disorders Nausea	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Gastrointestinal disorders Oral pain	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Gastrointestinal disorders Pancreatitis	3.7% 2/54 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Gastrointestinal disorders Vomiting	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
General disorders Chills	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
General disorders Death NOS	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
General disorders Edema limbs	3.7% 2/54 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
General disorders Pain	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Hepatobiliary disorders Hepatic failure	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Immune system disorders Anaphylaxis	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Infections and infestations Catheter related infection	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Infections and infestations Enterocolitis infectious	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Infections and infestations Eye infection	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	0.00% 0/60 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Infections and infestations Infections and infestations - Other	29.6% 16/54 • Number of events 21 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	33.3% 20/60 • Number of events 21 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Infections and infestations Sepsis	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Infections and infestations Skin infection	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	0.00% 0/60 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Infections and infestations Upper respiratory infection	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Injury, poisoning and procedural complications Vascular access complication	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Investigations Activated partial thromboplastin time prolonged	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Investigations Alanine aminotransferase increased	5.6% 3/54 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	8.3% 5/60 • Number of events 5 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Investigations Aspartate aminotransferase increased	7.4% 4/54 • Number of events 4 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	6.7% 4/60 • Number of events 4 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Investigations Blood bilirubin increased	5.6% 3/54 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.

Other adverse events
Measure	Reinduction Chemoimmunotherapy With Epratuzumab Once Weekly n=54 participants at risk Four weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 8, 15, 22. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, HD methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), ITT (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC	Reinduction Chemoimmunotherapy With Epratuzumab Twice Weekly n=60 participants at risk Eight 8 twice-weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 4, 8, 11, 15, 18, 22 \& 25. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, HD methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), ITT (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy. L-asparaginase: Given IM doxorubicin hydrochloride: Given IV therapeutic hydrocortisone: 40 mg/m2/day PO divided BID or TID vincristine sulfate: Given IV epratuzumab: Given IV cytarabine: Given IT prednisone: Given orally pegaspargase: Given IM dexrazoxane hydrochloride: Given IV methotrexate: Given IT etoposide: Given IV cyclophosphamide: Given IV leucovorin calcium: Given IV filgrastim: Given SC
Metabolism and nutrition disorders Hypokalemia	29.6% 16/54 • Number of events 16 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	26.7% 16/60 • Number of events 19 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Metabolism and nutrition disorders Hypomagnesemia	3.7% 2/54 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	0.00% 0/60 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Metabolism and nutrition disorders Hyponatremia	20.4% 11/54 • Number of events 11 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	15.0% 9/60 • Number of events 9 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Metabolism and nutrition disorders Hypophosphatemia	5.6% 3/54 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	8.3% 5/60 • Number of events 5 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Metabolism and nutrition disorders Tumor lysis syndrome	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Musculoskeletal and connective tissue disorders Arthralgia	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	0.00% 0/60 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Metabolism and nutrition disorders Hyperuricemia	3.7% 2/54 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	0.00% 0/60 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Metabolism and nutrition disorders Hypoalbuminemia	18.5% 10/54 • Number of events 10 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	11.7% 7/60 • Number of events 7 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Metabolism and nutrition disorders Hypocalcemia	16.7% 9/54 • Number of events 10 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	13.3% 8/60 • Number of events 8 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Blood and lymphatic system disorders Anemia	66.7% 36/54 • Number of events 45 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	68.3% 41/60 • Number of events 49 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Blood and lymphatic system disorders Febrile neutropenia	33.3% 18/54 • Number of events 18 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	36.7% 22/60 • Number of events 23 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Cardiac disorders Sinus bradycardia	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	0.00% 0/60 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Eye disorders Eye disorders - Other	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Eye disorders Eye pain	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Eye disorders Photophobia	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Gastrointestinal disorders Abdominal distension	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	0.00% 0/60 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Gastrointestinal disorders Abdominal pain	5.6% 3/54 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	0.00% 0/60 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Gastrointestinal disorders Diarrhea	3.7% 2/54 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	5.0% 3/60 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Gastrointestinal disorders Ileus	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	0.00% 0/60 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Gastrointestinal disorders Mucositis oral	7.4% 4/54 • Number of events 4 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	8.3% 5/60 • Number of events 5 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Metabolism and nutrition disorders Hypoglycemia	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Gastrointestinal disorders Nausea	5.6% 3/54 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	5.0% 3/60 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Gastrointestinal disorders Oral pain	3.7% 2/54 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Gastrointestinal disorders Pancreatitis	9.3% 5/54 • Number of events 5 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Gastrointestinal disorders Rectal hemorrhage	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	0.00% 0/60 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Gastrointestinal disorders Typhlitis	3.7% 2/54 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	0.00% 0/60 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Gastrointestinal disorders Vomiting	3.7% 2/54 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
General disorders Fatigue	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
General disorders Fever	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
General disorders Irritability	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	0.00% 0/60 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
General disorders Pain	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	6.7% 4/60 • Number of events 4 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Immune system disorders Anaphylaxis	3.7% 2/54 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	0.00% 0/60 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Infections and infestations Catheter related infection	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Infections and infestations Enterocolitis infectious	5.6% 3/54 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	5.0% 3/60 • Number of events 3 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Infections and infestations Infections and infestations - Other	51.9% 28/54 • Number of events 29 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	31.7% 19/60 • Number of events 20 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Infections and infestations Mucosal infection	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Infections and infestations Penile infection	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	0.00% 0/60 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Infections and infestations Sepsis	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	1.7% 1/60 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Infections and infestations Skin infection	0.00% 0/54 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	3.3% 2/60 • Number of events 2 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.
Infections and infestations Small intestine infection	1.9% 1/54 • Number of events 1 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.	0.00% 0/60 SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients (2) are not included in adverse event reporting for the once weekly arm.