Trial Outcomes & Findings for Biological Therapy, Sargramostim, and Isotretinoin in Treating Patients With Relapsed or Refractory Neuroblastoma (NCT NCT01334515)

Last Updated: 2019-10-21

Results Overview

Test for tolerability and monitor for the occurrence of too many unacceptable DLTs using a two-stage stopping rule: (Stage 1) Accrue 10 patients. If more than 1 experience at least one unacceptable DLT during the first treatment cycle, the regimen will be considered to have unacceptable toxicity, and accrual will be temporarily closed, to review all relevant data and consider modifying the regimen to improve safety. If 1 or no patients have an unacceptable DLT in the first treatment cycle, then continue. (Stage 2) Accrue 20 more patients. If 7 or more experience at least one unacceptable DLT in the first treatment cycle, temporarily close the study for possible dosing-safety modifications. If 6 or fewer have an unacceptable DLT in the first treatment cycle, it is reasonable to assume that the combination therapy is safe.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

52 participants

Primary outcome timeframe

Up to 10 courses

Results posted on

2019-10-21

Participant Flow

Participant milestones

Participant milestones
Measure	Disease Measured by Standard Radiographic Criteria Treatment (hu14.18-IL2 fusion protein and isotretinoin). Patients receive sargramostim (SC \[preferred\]) or IV over 2 hours on days 1-2 and 8-14, hu14.18-IL2 fusion protein IV over 4 hours on days 4-6, and isotretinoin PO twice daily on days 11-24. Treatment repeats every 28 days for 4-10 courses in the absence of disease progression or unacceptable toxicity. Patients in stratum-1 who achieve SD after course 4 are removed from protocol therapy. Patients in stratum-2 who achieve SD after course 4 receive 2 additional courses of study treatment. Patients may undergo blood and bone marrow sample collection periodically for correlative studies. hu14.18-IL2 fusion protein: Given IV isotretinoin: Given PO sargramostim: Given SC laboratory biomarker analysis: Correlative studies	Disease Evaluable Only by I-MIBG or BM Histology Treatment (hu14.18-IL2 fusion protein and isotretinoin). Patients receive sargramostim (SC \[preferred\]) or IV over 2 hours on days 1-2 and 8-14, hu14.18-IL2 fusion protein IV over 4 hours on days 4-6, and isotretinoin PO twice daily on days 11-24. Treatment repeats every 28 days for 4-10 courses in the absence of disease progression or unacceptable toxicity. Patients in stratum-1 who achieve SD after course 4 are removed from protocol therapy. Patients in stratum-2 who achieve SD after course 4 receive 2 additional courses of study treatment. Patients may undergo blood and bone marrow sample collection periodically for correlative studies. hu14.18-IL2 fusion protein: Given IV isotretinoin: Given PO sargramostim: Given SC laboratory biomarker analysis: Correlative studies
Overall Study STARTED	16	36
Overall Study COMPLETED	4	7
Overall Study NOT COMPLETED	12	29

Reasons for withdrawal

Reasons for withdrawal
Measure	Disease Measured by Standard Radiographic Criteria Treatment (hu14.18-IL2 fusion protein and isotretinoin). Patients receive sargramostim (SC \[preferred\]) or IV over 2 hours on days 1-2 and 8-14, hu14.18-IL2 fusion protein IV over 4 hours on days 4-6, and isotretinoin PO twice daily on days 11-24. Treatment repeats every 28 days for 4-10 courses in the absence of disease progression or unacceptable toxicity. Patients in stratum-1 who achieve SD after course 4 are removed from protocol therapy. Patients in stratum-2 who achieve SD after course 4 receive 2 additional courses of study treatment. Patients may undergo blood and bone marrow sample collection periodically for correlative studies. hu14.18-IL2 fusion protein: Given IV isotretinoin: Given PO sargramostim: Given SC laboratory biomarker analysis: Correlative studies	Disease Evaluable Only by I-MIBG or BM Histology Treatment (hu14.18-IL2 fusion protein and isotretinoin). Patients receive sargramostim (SC \[preferred\]) or IV over 2 hours on days 1-2 and 8-14, hu14.18-IL2 fusion protein IV over 4 hours on days 4-6, and isotretinoin PO twice daily on days 11-24. Treatment repeats every 28 days for 4-10 courses in the absence of disease progression or unacceptable toxicity. Patients in stratum-1 who achieve SD after course 4 are removed from protocol therapy. Patients in stratum-2 who achieve SD after course 4 receive 2 additional courses of study treatment. Patients may undergo blood and bone marrow sample collection periodically for correlative studies. hu14.18-IL2 fusion protein: Given IV isotretinoin: Given PO sargramostim: Given SC laboratory biomarker analysis: Correlative studies
Overall Study Adverse Event	1	6
Overall Study Death	1	0
Overall Study Lack of Efficacy	8	21
Overall Study Physician Decision	1	1
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

Biological Therapy, Sargramostim, and Isotretinoin in Treating Patients With Relapsed or Refractory Neuroblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Disease Measured by Standard Radiographic Criteria n=16 Participants Treatment (hu14.18-IL2 fusion protein and isotretinoin). Patients receive sargramostim (SC \[preferred\]) or IV over 2 hours on days 1-2 and 8-14, hu14.18-IL2 fusion protein IV over 4 hours on days 4-6, and isotretinoin PO twice daily on days 11-24. Treatment repeats every 28 days for 4-10 courses in the absence of disease progression or unacceptable toxicity. Patients in stratum-1 who achieve SD after course 4 are removed from protocol therapy. Patients in stratum-2 who achieve SD after course 4 receive 2 additional courses of study treatment. Patients may undergo blood and bone marrow sample collection periodically for correlative studies. hu14.18-IL2 fusion protein: Given IV isotretinoin: Given PO sargramostim: Given SC laboratory biomarker analysis: Correlative studies	Disease Evaluable Only by I-MIBG or BM Histology n=36 Participants Treatment (hu14.18-IL2 fusion protein and isotretinoin). Patients receive sargramostim (SC \[preferred\]) or IV over 2 hours on days 1-2 and 8-14, hu14.18-IL2 fusion protein IV over 4 hours on days 4-6, and isotretinoin PO twice daily on days 11-24. Treatment repeats every 28 days for 4-10 courses in the absence of disease progression or unacceptable toxicity. Patients in stratum-1 who achieve SD after course 4 are removed from protocol therapy. Patients in stratum-2 who achieve SD after course 4 receive 2 additional courses of study treatment. Patients may undergo blood and bone marrow sample collection periodically for correlative studies. hu14.18-IL2 fusion protein: Given IV isotretinoin: Given PO sargramostim: Given SC laboratory biomarker analysis: Correlative studies	Total n=52 Participants Total of all reporting groups
Age, Continuous	6.94 years n=5 Participants	8.75 years n=7 Participants	8.31 years n=5 Participants
Age, Categorical <=18 years	15 Participants n=5 Participants	32 Participants n=7 Participants	47 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	4 Participants n=7 Participants	5 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	6 Participants n=5 Participants	12 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	24 Participants n=7 Participants	34 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	1 Participants n=7 Participants	1 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	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	25 Participants n=7 Participants	36 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	2 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=5 Participants	30 Participants n=7 Participants	41 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment United States	14 participants n=5 Participants	33 participants n=7 Participants	47 participants n=5 Participants
Region of Enrollment Canada	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 10 courses

Population: This outcome measure evaluates the first 30 patients to enroll and who receive at least one dose of hu14.18-IL2.

Outcome measures

Outcome measures
Measure	Disease Measured by Standard Radiographic Criteria n=10 Participants Treatment (hu14.18-IL2 fusion protein and isotretinoin). Patients receive sargramostim (SC \[preferred\]) or IV over 2 hours on days 1-2 and 8-14, hu14.18-IL2 fusion protein IV over 4 hours on days 4-6, and isotretinoin PO twice daily on days 11-24. Treatment repeats every 28 days for 4-10 courses in the absence of disease progression or unacceptable toxicity. Patients in stratum-1 who achieve SD after course 4 are removed from protocol therapy. Patients in stratum-2 who achieve SD after course 4 receive 2 additional courses of study treatment. Patients may undergo blood and bone marrow sample collection periodically for correlative studies. hu14.18-IL2 fusion protein: Given IV isotretinoin: Given PO sargramostim: Given SC laboratory biomarker analysis: Correlative studies	Disease Evaluable Only by I-MIBG or BM Histology n=20 Participants Treatment (hu14.18-IL2 fusion protein and isotretinoin). Patients receive sargramostim (SC \[preferred\]) or IV over 2 hours on days 1-2 and 8-14, hu14.18-IL2 fusion protein IV over 4 hours on days 4-6, and isotretinoin PO twice daily on days 11-24. Treatment repeats every 28 days for 4-10 courses in the absence of disease progression or unacceptable toxicity. Patients in stratum-1 who achieve SD after course 4 are removed from protocol therapy. Patients in stratum-2 who achieve SD after course 4 receive 2 additional courses of study treatment. Patients may undergo blood and bone marrow sample collection periodically for correlative studies. hu14.18-IL2 fusion protein: Given IV isotretinoin: Given PO sargramostim: Given SC laboratory biomarker analysis: Correlative studies
Number of Patients With Unacceptable Dose Limiting Toxicities (DLTs) Patients with Unacceptable DLTs	1 participants	2 participants
Number of Patients With Unacceptable Dose Limiting Toxicities (DLTs) Patients without Unacceptable DLTs	9 participants	18 participants

SECONDARY outcome

Timeframe: Every two cycles (each cycle lasts 28 days)

Population: Patients will be evaluable for inclusion in the analysis of response if they have an event at any time on the study or if they complete at least 2 cycles of hu14.18-IL2 therapy. Patients who go off-protocol therapy prior to the completion of 2 cycles due to parent/family choice and/or due to toxicity will not be considered evaluable for response.

Number of patients where best overall response is a complete response (CR)-\[disappearance of all target lesions and disappearance of any other measureable disease\], a very Good Partial Response (VGPR)- \[\>90% decrease of the disease measurement for CT/MRI lesions, taking as reference the disease measurement done to confirm measurable disease at study entry. Non-target CT/MRI lesions stable to smaller in size\], or partial Response (PR)- \[\>= 30% decrease in the disease measurement, taking as reference the disease measurement done to confirm measurable disease at study entry. Non-target CT/MRI lesions stable to smaller in size\], and maintains the response. It is possible that a subject's response to therapy may not occur until after several months of treatment. In order to prevent bias, the maximum duration of time/treatment over which a subject's response is to be assessed for determination of the best overall response is after the completion of up to 10 courses.

Outcome measures

Outcome measures
Measure	Disease Measured by Standard Radiographic Criteria n=15 Participants Treatment (hu14.18-IL2 fusion protein and isotretinoin). Patients receive sargramostim (SC \[preferred\]) or IV over 2 hours on days 1-2 and 8-14, hu14.18-IL2 fusion protein IV over 4 hours on days 4-6, and isotretinoin PO twice daily on days 11-24. Treatment repeats every 28 days for 4-10 courses in the absence of disease progression or unacceptable toxicity. Patients in stratum-1 who achieve SD after course 4 are removed from protocol therapy. Patients in stratum-2 who achieve SD after course 4 receive 2 additional courses of study treatment. Patients may undergo blood and bone marrow sample collection periodically for correlative studies. hu14.18-IL2 fusion protein: Given IV isotretinoin: Given PO sargramostim: Given SC laboratory biomarker analysis: Correlative studies	Disease Evaluable Only by I-MIBG or BM Histology n=30 Participants Treatment (hu14.18-IL2 fusion protein and isotretinoin). Patients receive sargramostim (SC \[preferred\]) or IV over 2 hours on days 1-2 and 8-14, hu14.18-IL2 fusion protein IV over 4 hours on days 4-6, and isotretinoin PO twice daily on days 11-24. Treatment repeats every 28 days for 4-10 courses in the absence of disease progression or unacceptable toxicity. Patients in stratum-1 who achieve SD after course 4 are removed from protocol therapy. Patients in stratum-2 who achieve SD after course 4 receive 2 additional courses of study treatment. Patients may undergo blood and bone marrow sample collection periodically for correlative studies. hu14.18-IL2 fusion protein: Given IV isotretinoin: Given PO sargramostim: Given SC laboratory biomarker analysis: Correlative studies
Overall Response Evaluated in This Study Using the New International Criteria Proposed by the Revised Response Evaluation Criteria in Solid Tumors (RECIST) Responders	1 participants	6 participants
Overall Response Evaluated in This Study Using the New International Criteria Proposed by the Revised Response Evaluation Criteria in Solid Tumors (RECIST) Non-Responders	14 participants	24 participants

Adverse Events

Disease Measured by Standard Radiographic Criteria

Serious events: 7 serious events

Other events: 13 other events

Deaths: 0 deaths

Disease Evaluable Only by I-MIBG or BM Histology

Serious events: 18 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Results Reporting Coordinator

Children's Oncology Group

Phone: 352-273-0567

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	Disease Measured by Standard Radiographic Criteria n=16 participants at risk Treatment (hu14.18-IL2 fusion protein and isotretinoin). Patients receive sargramostim (SC \[preferred\]) or IV over 2 hours on days 1-2 and 8-14, hu14.18-IL2 fusion protein IV over 4 hours on days 4-6, and isotretinoin PO twice daily on days 11-24. Treatment repeats every 28 days for 4-10 courses in the absence of disease progression or unacceptable toxicity. Patients in stratum-1 who achieve SD after course 4 are removed from protocol therapy. Patients in stratum-2 who achieve SD after course 4 receive 2 additional courses of study treatment. Patients may undergo blood and bone marrow sample collection periodically for correlative studies. hu14.18-IL2 fusion protein: Given IV isotretinoin: Given PO sargramostim: Given SC laboratory biomarker analysis: Correlative studies	Disease Evaluable Only by I-MIBG or BM Histology n=36 participants at risk Treatment (hu14.18-IL2 fusion protein and isotretinoin). Patients receive sargramostim (SC \[preferred\]) or IV over 2 hours on days 1-2 and 8-14, hu14.18-IL2 fusion protein IV over 4 hours on days 4-6, and isotretinoin PO twice daily on days 11-24. Treatment repeats every 28 days for 4-10 courses in the absence of disease progression or unacceptable toxicity. Patients in stratum-1 who achieve SD after course 4 are removed from protocol therapy. Patients in stratum-2 who achieve SD after course 4 receive 2 additional courses of study treatment. Patients may undergo blood and bone marrow sample collection periodically for correlative studies. hu14.18-IL2 fusion protein: Given IV isotretinoin: Given PO sargramostim: Given SC laboratory biomarker analysis: Correlative studies
Blood and lymphatic system disorders Anemia	6.2% 1/16 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	0.00% 0/36 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Gastrointestinal disorders Vomiting	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
General disorders Death NOS	6.2% 1/16 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	0.00% 0/36 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
General disorders Fever	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	5.6% 2/36 • Number of events 2 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
General disorders Malaise	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
General disorders Pain	6.2% 1/16 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	5.6% 2/36 • Number of events 2 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Investigations Alanine aminotransferase increased	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	8.3% 3/36 • Number of events 3 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Investigations Aspartate aminotransferase increased	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	8.3% 3/36 • Number of events 3 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Investigations Blood bilirubin increased	25.0% 4/16 • Number of events 5 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	16.7% 6/36 • Number of events 7 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Investigations GGT increased	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Investigations Platelet count decreased	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Metabolism and nutrition disorders Anorexia	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Metabolism and nutrition disorders Dehydration	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Metabolism and nutrition disorders Hypercalcemia	6.2% 1/16 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	0.00% 0/36 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Metabolism and nutrition disorders Hypoalbuminemia	6.2% 1/16 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	0.00% 0/36 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Metabolism and nutrition disorders Hypocalcemia	6.2% 1/16 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Metabolism and nutrition disorders Hypokalemia	6.2% 1/16 • Number of events 2 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Metabolism and nutrition disorders Hypophosphatemia	6.2% 1/16 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	0.00% 0/36 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Musculoskeletal and connective tissue disorders Back pain	6.2% 1/16 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	0.00% 0/36 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Nervous system disorders Depressed level of consciousness	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Respiratory, thoracic and mediastinal disorders Hypoxia	6.2% 1/16 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Respiratory, thoracic and mediastinal disorders Pleural effusion	6.2% 1/16 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	0.00% 0/36 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Respiratory, thoracic and mediastinal disorders Sore throat	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Skin and subcutaneous tissue disorders Erythroderma	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Skin and subcutaneous tissue disorders Rash maculo-papular	6.2% 1/16 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	0.00% 0/36 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Vascular disorders Capillary leak syndrome	18.8% 3/16 • Number of events 4 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	5.6% 2/36 • Number of events 2 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Vascular disorders Hypotension	6.2% 1/16 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.

Other adverse events
Measure	Disease Measured by Standard Radiographic Criteria n=16 participants at risk Treatment (hu14.18-IL2 fusion protein and isotretinoin). Patients receive sargramostim (SC \[preferred\]) or IV over 2 hours on days 1-2 and 8-14, hu14.18-IL2 fusion protein IV over 4 hours on days 4-6, and isotretinoin PO twice daily on days 11-24. Treatment repeats every 28 days for 4-10 courses in the absence of disease progression or unacceptable toxicity. Patients in stratum-1 who achieve SD after course 4 are removed from protocol therapy. Patients in stratum-2 who achieve SD after course 4 receive 2 additional courses of study treatment. Patients may undergo blood and bone marrow sample collection periodically for correlative studies. hu14.18-IL2 fusion protein: Given IV isotretinoin: Given PO sargramostim: Given SC laboratory biomarker analysis: Correlative studies	Disease Evaluable Only by I-MIBG or BM Histology n=36 participants at risk Treatment (hu14.18-IL2 fusion protein and isotretinoin). Patients receive sargramostim (SC \[preferred\]) or IV over 2 hours on days 1-2 and 8-14, hu14.18-IL2 fusion protein IV over 4 hours on days 4-6, and isotretinoin PO twice daily on days 11-24. Treatment repeats every 28 days for 4-10 courses in the absence of disease progression or unacceptable toxicity. Patients in stratum-1 who achieve SD after course 4 are removed from protocol therapy. Patients in stratum-2 who achieve SD after course 4 receive 2 additional courses of study treatment. Patients may undergo blood and bone marrow sample collection periodically for correlative studies. hu14.18-IL2 fusion protein: Given IV isotretinoin: Given PO sargramostim: Given SC laboratory biomarker analysis: Correlative studies
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	8.3% 3/36 • Number of events 3 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Metabolism and nutrition disorders Obesity	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Blood and lymphatic system disorders Anemia	56.2% 9/16 • Number of events 11 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	30.6% 11/36 • Number of events 11 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Musculoskeletal and connective tissue disorders Back pain	6.2% 1/16 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	5.6% 2/36 • Number of events 3 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Cardiac disorders Cardiac disorders - Other	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Cardiac disorders Mitral valve disease	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Ear and labyrinth disorders Hearing impaired	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	8.3% 3/36 • Number of events 3 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Eye disorders Eye disorders - Other	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Eye disorders Photophobia	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Gastrointestinal disorders Abdominal pain	6.2% 1/16 • Number of events 2 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	13.9% 5/36 • Number of events 5 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Gastrointestinal disorders Gastroesophageal reflux disease	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Gastrointestinal disorders Nausea	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	5.6% 2/36 • Number of events 3 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Gastrointestinal disorders Small intestinal obstruction	6.2% 1/16 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	0.00% 0/36 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Gastrointestinal disorders Vomiting	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
General disorders Fatigue	12.5% 2/16 • Number of events 2 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	0.00% 0/36 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
General disorders Fever	6.2% 1/16 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	27.8% 10/36 • Number of events 22 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
General disorders Pain	12.5% 2/16 • Number of events 2 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	16.7% 6/36 • Number of events 10 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Immune system disorders Allergic reaction	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	5.6% 2/36 • Number of events 2 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Infections and infestations Catheter related infection	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	5.6% 2/36 • Number of events 3 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Infections and infestations Enterocolitis infectious	6.2% 1/16 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	0.00% 0/36 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Infections and infestations Infections and infestations - Other	12.5% 2/16 • Number of events 4 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Infections and infestations Lung infection	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Infections and infestations Otitis media	6.2% 1/16 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	0.00% 0/36 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Infections and infestations Upper respiratory infection	6.2% 1/16 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Investigations Alanine aminotransferase increased	18.8% 3/16 • Number of events 4 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	38.9% 14/36 • Number of events 20 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Investigations Alkaline phosphatase increased	12.5% 2/16 • Number of events 2 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	0.00% 0/36 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Investigations Aspartate aminotransferase increased	12.5% 2/16 • Number of events 2 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	30.6% 11/36 • Number of events 13 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Investigations Blood bilirubin increased	12.5% 2/16 • Number of events 4 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	11.1% 4/36 • Number of events 10 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Investigations GGT increased	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	5.6% 2/36 • Number of events 4 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Investigations Lymphocyte count decreased	12.5% 2/16 • Number of events 3 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	27.8% 10/36 • Number of events 16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Investigations Neutrophil count decreased	12.5% 2/16 • Number of events 2 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	13.9% 5/36 • Number of events 6 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Investigations Platelet count decreased	31.2% 5/16 • Number of events 7 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	30.6% 11/36 • Number of events 20 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Investigations Weight gain	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	2.8% 1/36 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Investigations Weight loss	6.2% 1/16 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	0.00% 0/36 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Investigations White blood cell decreased	6.2% 1/16 • Number of events 2 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	22.2% 8/36 • Number of events 9 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Metabolism and nutrition disorders Anorexia	0.00% 0/16 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	8.3% 3/36 • Number of events 3 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Metabolism and nutrition disorders Hyperglycemia	31.2% 5/16 • Number of events 5 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	5.6% 2/36 • Number of events 4 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.
Metabolism and nutrition disorders Hypernatremia	6.2% 1/16 • Number of events 1 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.	0.00% 0/36 SAE field contains NCI Common Toxicity Criteria for Adverse Effects (CTCAE) 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. Only Grade 3 and higher Adverse Events were collected/assessed in this study.