Trial Outcomes & Findings for Comparing Two Different Myeloablation Therapies in Treating Young Patients Who Are Undergoing a Stem Cell Transplant for High-Risk Neuroblastoma (NCT NCT00567567)

NCT ID: NCT00567567

Last Updated: 2022-04-28

Results Overview

Comparison of EFS curves, starting from the time of randomization, by treatment group (single CEM vs. tandem CEM)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

665 participants

Primary outcome timeframe

Three years, from time of randomization

Results posted on

2022-04-28

Participant Flow

Participant milestones

Participant milestones
Measure	Single HST (CEM) Induction therapy + single myeloablative consolidation	Tandem HST (CEM), Randomly Assigned Induction therapy + tandem myeloablative consolidation	Not Assigned Patients that either failed during Induction therapy or refused randomization
Overall Study STARTED	210	176	279
Overall Study COMPLETED	58	42	1
Overall Study NOT COMPLETED	152	134	278

Reasons for withdrawal

Reasons for withdrawal
Measure	Single HST (CEM) Induction therapy + single myeloablative consolidation	Tandem HST (CEM), Randomly Assigned Induction therapy + tandem myeloablative consolidation	Not Assigned Patients that either failed during Induction therapy or refused randomization
Overall Study Adverse Event	0	2	5
Overall Study Death	8	1	5
Overall Study Lack of Efficacy	16	17	48
Overall Study Lost to Follow-up	0	0	1
Overall Study Physician Decision	16	18	84
Overall Study Withdrawal by Subject	0	0	2
Overall Study Ineligible	4	0	9
Overall Study Refusal by patient/parent/guardian	9	16	122
Overall Study Enrolled another COG therapeutic study	99	80	0
Overall Study Unable adequate stem cell for transplant	0	0	2

Baseline Characteristics

Comparing Two Different Myeloablation Therapies in Treating Young Patients Who Are Undergoing a Stem Cell Transplant for High-Risk Neuroblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Single HST (CEM) n=210 Participants Induction therapy + single myeloablative consolidation	Tandem HST (CEM), Randomly Assigned n=176 Participants Induction therapy + tandem myeloablative consolidation	Not Assigned n=279 Participants Patients that either failed during Induction therapy or refused randomization	Total n=665 Participants Total of all reporting groups
Age, Categorical <=18 years	208 Participants n=5 Participants	176 Participants n=7 Participants	277 Participants n=5 Participants	661 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	3.2 Years STANDARD_DEVIATION 2.9 • n=5 Participants	2.9 Years STANDARD_DEVIATION 2.4 • n=7 Participants	3.4 Years STANDARD_DEVIATION 2.8 • n=5 Participants	3.2 Years STANDARD_DEVIATION 2.7 • n=4 Participants
Sex: Female, Male Female	95 Participants n=5 Participants	78 Participants n=7 Participants	118 Participants n=5 Participants	291 Participants n=4 Participants
Sex: Female, Male Male	115 Participants n=5 Participants	98 Participants n=7 Participants	161 Participants n=5 Participants	374 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	22 Participants n=5 Participants	26 Participants n=7 Participants	30 Participants n=5 Participants	78 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	181 Participants n=5 Participants	145 Participants n=7 Participants	233 Participants n=5 Participants	559 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants	5 Participants n=7 Participants	16 Participants n=5 Participants	28 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	8 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants	23 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Black or African American	23 Participants n=5 Participants	18 Participants n=7 Participants	40 Participants n=5 Participants	81 Participants n=4 Participants
Race (NIH/OMB) White	157 Participants n=5 Participants	132 Participants n=7 Participants	203 Participants n=5 Participants	492 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	20 Participants n=5 Participants	21 Participants n=7 Participants	23 Participants n=5 Participants	64 Participants n=4 Participants
Region of Enrollment New Zealand	3 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants	7 participants n=4 Participants
Region of Enrollment Canada	19 participants n=5 Participants	21 participants n=7 Participants	23 participants n=5 Participants	63 participants n=4 Participants
Region of Enrollment United States	176 participants n=5 Participants	146 participants n=7 Participants	243 participants n=5 Participants	565 participants n=4 Participants
Region of Enrollment Australia	11 participants n=5 Participants	8 participants n=7 Participants	10 participants n=5 Participants	29 participants n=4 Participants
Region of Enrollment Switzerland	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants

PRIMARY outcome

Timeframe: Three years, from time of randomization

Population: All eligible, randomized patients.

Comparison of EFS curves, starting from the time of randomization, by treatment group (single CEM vs. tandem CEM)

Outcome measures

Outcome measures
Measure	Single HST (CEM) n=179 Participants Induction therapy + single myeloablative consolidation	Tandem HST (CEM), Randomly Assigned n=176 Participants Induction therapy + tandem myeloablative consolidation	Not Assigned Patients that either failed during Induction therapy or refused randomization
Event-free Survival Rate	48.8 percent probability Interval 41.1 to 56.5	61.8 percent probability Interval 53.8 to 69.8	—

PRIMARY outcome

Timeframe: Study enrollment to the end of induction therapy

Population: Eligible patients evaluated for response at the end of induction therapy.

Per the International Response Criteria: measurable tumor defined as product of longest x widest perpendicular diameter. Elevated catecholamine levels, tumor cell invasion of bone marrow also considered measurable tumor. Complete Response (CR)-no evidence of primary tumor or metastases. Very Good Partial Response (VGPR)-\>90% reduction of primary tumor; no metastases; no new bone lesions, all pre-existing lesions improved. Partial Response (PR)-50-90% reduction of primary tumor; \>50% reduction in measurable sites of metastases; 0-1 bone marrow samples with tumor; number of positive bone sites decreased by \>50%. Mixed Response (MR)-\>50% reduction of any measurable lesion (primary or metastases) with \<50% reduction in other sites; no new lesions; \<25% increase in any existing lesion. No Response (NR)-no new lesions; \<50% reduction but \<25% increase in any existing legions. Progressive Disease (PD)-any new/increased measurable lesion by \>25%; previous negative marrow positive.

Outcome measures

Outcome measures
Measure	Single HST (CEM) n=206 Participants Induction therapy + single myeloablative consolidation	Tandem HST (CEM), Randomly Assigned n=176 Participants Induction therapy + tandem myeloablative consolidation	Not Assigned n=233 Participants Patients that either failed during Induction therapy or refused randomization
Response After Induction Therapy	0.54 Proportion participants that responded Interval 0.47 to 0.61	0.48 Proportion participants that responded Interval 0.41 to 0.56	0.35 Proportion participants that responded Interval 0.29 to 0.41

PRIMARY outcome

Timeframe: Up to 3 years

Population: Eligible patients randomized or assigned to the single HST (CEM) treatment arm who also received boost radiation.

Cumulative incidence rate of local recurrence comparison between ANBL0532 patients randomized or assigned to receive single CEM transplant and boost radiation versus the historical A3973 patients who were transplanted and received boost radiation.

Outcome measures

Outcome measures
Measure	Single HST (CEM) n=77 Participants Induction therapy + single myeloablative consolidation	Tandem HST (CEM), Randomly Assigned Induction therapy + tandem myeloablative consolidation	Not Assigned Patients that either failed during Induction therapy or refused randomization
Incidence Rate of Local Recurrence	15.7 Percentage 3-year cumulative incidence Interval 7.5 to 23.9	—	—

SECONDARY outcome

Timeframe: Through completion of a participant's first cycle during induction, including treatment delays, assessed up to 39 days

Population: Eligible patients with available polymorphism and neutropenia toxicity data.

A logistic regression model will be used to test the ability of the number of days of neutropenia to predict the presence of a polymorphism.

Outcome measures

Outcome measures
Measure	Single HST (CEM) n=117 Participants Induction therapy + single myeloablative consolidation	Tandem HST (CEM), Randomly Assigned n=103 Participants Induction therapy + tandem myeloablative consolidation	Not Assigned n=129 Participants Patients that either failed during Induction therapy or refused randomization
Duration of Greater Than or Equal to Grade 3 Neutropenia	7 Days Interval 0.0 to 20.0	7 Days Interval 0.0 to 39.0	7 Days Interval 0.0 to 35.0

SECONDARY outcome

Timeframe: Through completion of a participant's first cycle during induction, including treatment delays, assessed up to 46 days

Population: Eligible patients with available polymorphism and thrombocytopenia toxicity data.

A logistic regression model will be used to test the ability of the number of days of thrombocytopenia to predict the presence of a polymorphism.

Outcome measures

Outcome measures
Measure	Single HST (CEM) n=117 Participants Induction therapy + single myeloablative consolidation	Tandem HST (CEM), Randomly Assigned n=103 Participants Induction therapy + tandem myeloablative consolidation	Not Assigned n=129 Participants Patients that either failed during Induction therapy or refused randomization
Duration of Greater Than or Equal to Grade 3 Thrombocytopenia	4 Days Interval 0.0 to 30.0	4 Days Interval 0.0 to 46.0	4 Days Interval 0.0 to 44.0

SECONDARY outcome

Timeframe: Through completion of a participant's first two cycles during induction, including treatment delays, assessed up to 69 days

Population: Eligible patients with available polymorphism data and response data after two cycles of induction therapy. Measure value is the proportion of patients with a polymorphism.

A chi-square test will be used to test whether the response rate after two cycles of induction therapy and the presence of a polymorphism are independent in the study population.

Outcome measures

Outcome measures
Measure	Single HST (CEM) n=101 Participants Induction therapy + single myeloablative consolidation	Tandem HST (CEM), Randomly Assigned n=92 Participants Induction therapy + tandem myeloablative consolidation	Not Assigned n=109 Participants Patients that either failed during Induction therapy or refused randomization
Proportion of Patients With a Polymorphism	0.96 Proportion of patients	0.96 Proportion of patients	0.97 Proportion of patients

SECONDARY outcome

Timeframe: Up to 3 years

Population: All eligible patients enrolled on ANBL0532.

Percentage of patients who achieved a surgical complete resection

Outcome measures

Outcome measures
Measure	Single HST (CEM) n=206 Participants Induction therapy + single myeloablative consolidation	Tandem HST (CEM), Randomly Assigned n=176 Participants Induction therapy + tandem myeloablative consolidation	Not Assigned n=270 Participants Patients that either failed during Induction therapy or refused randomization
Surgical Response	83.98 Percentage of patients	84.09 Percentage of patients	58.89 Percentage of patients

SECONDARY outcome

Timeframe: Up to 3 years

Population: All eligible patients enrolled on ANBL0532.

The Percentage of patients who experienced surgical or radiotherapy complications will be calculated. The complications are: bowel obstruction, chylous leaf, renal injury/atrophy/loss and diarrhea.

Outcome measures

Outcome measures
Measure	Single HST (CEM) n=206 Participants Induction therapy + single myeloablative consolidation	Tandem HST (CEM), Randomly Assigned n=176 Participants Induction therapy + tandem myeloablative consolidation	Not Assigned n=270 Participants Patients that either failed during Induction therapy or refused randomization
Type of Surgical or Radiotherapy Complication	13.11 Percentage of patients	12.50 Percentage of patients	11.85 Percentage of patients

SECONDARY outcome

Timeframe: Up to 5 years

Population: All eligible patients enrolled on ANBL0532.

Percentage of patients with primary tumors with intraspinal extension.

Outcome measures

Outcome measures
Measure	Single HST (CEM) n=206 Participants Induction therapy + single myeloablative consolidation	Tandem HST (CEM), Randomly Assigned n=176 Participants Induction therapy + tandem myeloablative consolidation	Not Assigned n=270 Participants Patients that either failed during Induction therapy or refused randomization
Intraspinal Extension	8.25 Percentage of patients	9.66 Percentage of patients	7.78 Percentage of patients

SECONDARY outcome

Timeframe: Day 1 of each course

Population: Eligible patients evaluated for peak serum concentration level of isotretinoin.

Median peak serum concentration level of isotretinoin for patients enrolled on ANBL0532

Outcome measures

Outcome measures
Measure	Single HST (CEM) n=91 Participants Induction therapy + single myeloablative consolidation	Tandem HST (CEM), Randomly Assigned n=76 Participants Induction therapy + tandem myeloablative consolidation	Not Assigned n=49 Participants Patients that either failed during Induction therapy or refused randomization
Peak Serum Concentration of Isotretinoin in Patients Enrolled on Either A3973, ANBL0032, ANBL0931, ANBL0532 and Future High Risk Studies	1.00 Micromolar Interval 0.0 to 9.22	1.36 Micromolar Interval 0.0 to 12.93	1.26 Micromolar Interval 0.0 to 11.78

SECONDARY outcome

Timeframe: At baseline

Population: Data were not collected to assess this study aim.

To determine if pharmacogenomic variations are predictive of EFS, a logrank test comparison of patients with vs without a given polymorphism will be made. A Fisher's exact test will test for association of the presence of a polymorphism with the occurrence of systemic toxicity (CTC grade 3 or 4 skin, hypercalcemia, or hepatic toxicity). These tests will be performed for UGT1A1, UGT2B7, CYP2C8 and CYP3A7 alleles.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 of courses 1-2

Population: Eligible patients evaluated for topotecan systemic clearance.

Median topotecan systemic clearance for courses 1 and 2.

Outcome measures

Outcome measures
Measure	Single HST (CEM) n=82 Participants Induction therapy + single myeloablative consolidation	Tandem HST (CEM), Randomly Assigned n=76 Participants Induction therapy + tandem myeloablative consolidation	Not Assigned n=103 Participants Patients that either failed during Induction therapy or refused randomization
Topotecan Systemic Clearance	28.1 L/h/m2 Interval 14.9 to 49.4	28.1 L/h/m2 Interval 11.6 to 42.7	28.5 L/h/m2 Interval 16.3 to 54.7

SECONDARY outcome

Timeframe: Up to 6 months (end of therapy)

Population: Data were not collected to assess this study aim.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 6 months after completion of assigned myeloablation therapy

Population: All eligible patients that had CD3, CD4 and CD8T-cell count evaluated at the end of reporting period 3.

A descriptive comparison of the median number of T-cells (CD3, CD4, CD8) between treatment arms (single vs. tandem myeloablative regimens) will be performed.

Outcome measures

Outcome measures
Measure	Single HST (CEM) n=43 Participants Induction therapy + single myeloablative consolidation	Tandem HST (CEM), Randomly Assigned n=43 Participants Induction therapy + tandem myeloablative consolidation	Not Assigned Patients that either failed during Induction therapy or refused randomization
Enumeration of Peripheral Blood Cluster of Differentiation (CD)3, CD4, and CD8 Cells CD3	200 cells/mm^3 Interval 23.0 to 1549.0	255.5 cells/mm^3 Interval 13.0 to 2987.0	—
Enumeration of Peripheral Blood Cluster of Differentiation (CD)3, CD4, and CD8 Cells CD4	73 cells/mm^3 Interval 8.0 to 626.0	81 cells/mm^3 Interval 4.0 to 1186.0	—
Enumeration of Peripheral Blood Cluster of Differentiation (CD)3, CD4, and CD8 Cells CD8	104 cells/mm^3 Interval 8.0 to 1170.0	151 cells/mm^3 Interval 4.0 to 2529.0	—

SECONDARY outcome

Timeframe: Baseline

Population: Data were not collected to assess this study aim.

Will be calculated overall and by treatment arm.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 3 years

Population: All eligible patients non-randomly assigned to single CEM

Kaplan-Meier curves of EFS will be plotted, and the proportion of responders to induction therapy will be tabulated.

Outcome measures

Outcome measures
Measure	Single HST (CEM) n=27 Participants Induction therapy + single myeloablative consolidation	Tandem HST (CEM), Randomly Assigned Induction therapy + tandem myeloablative consolidation	Not Assigned Patients that either failed during Induction therapy or refused randomization
EFS Pts Non-randomly Assigned to Single CEM (12-18 Mths, Stg. 4, MYCN Nonamplified Tumor/Unfavorable or Indeterminant Histopathology/Diploid DNA Content & Pts>547 Days, Stg.3, MYCN Nonamplified Tumor AND Unfavorable or Indeterminant Histopathology).	73.1 percent probability Interval 55.1 to 91.2	—	—

SECONDARY outcome

Timeframe: Up to 3 years

Kaplan-Meier curves of OS will be plotted, and the proportion of responders to induction therapy will be tabulated.

Outcome measures

Outcome measures
Measure	Single HST (CEM) n=27 Participants Induction therapy + single myeloablative consolidation	Tandem HST (CEM), Randomly Assigned Induction therapy + tandem myeloablative consolidation	Not Assigned Patients that either failed during Induction therapy or refused randomization
OS in Patients 12-18 Months, Stage 4, MYCN Nonamplified Tumor/Unfavorable Histopathology/Diploid DNA Content/Indeterminant Histology/Ploidy and Patients > 547 Days, Stage 3, MYCN Nonamplified Tumor AND Unfavorable Histopathology/Indeterminant Histology	81.0 percent probability Interval 65.1 to 96.9	—	—

Adverse Events

Single HST (CEM)

Serious events: 16 serious events

Other events: 196 other events

Deaths: 0 deaths

Tandem HST (CEM), Randomly Assigned

Serious events: 15 serious events

Other events: 163 other events

Deaths: 0 deaths

Not Assigned

Serious events: 12 serious events

Other events: 230 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	Single HST (CEM) n=206 participants at risk Induction therapy + single myeloablative consolidation	Tandem HST (CEM), Randomly Assigned n=176 participants at risk Induction therapy + tandem myeloablative consolidation	Not Assigned n=269 participants at risk Patients that either failed during Induction therapy or refused randomization
Blood and lymphatic system disorders 13200-Anemia	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.74% 2/269 • Number of events 2 We've excluded the ineligibles from this table.
Blood and lymphatic system disorders 17200-Blood and lymphatic system disorders - Other specify	0.00% 0/206 We've excluded the ineligibles from this table.	1.7% 3/176 • Number of events 3 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Blood and lymphatic system disorders 25800-Disseminated intravascular coagulation	0.97% 2/206 • Number of events 2 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.37% 1/269 • Number of events 1 We've excluded the ineligibles from this table.
Blood and lymphatic system disorders 33300-Febrile neutropenia	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.57% 1/176 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Blood and lymphatic system disorders 39600-Hemolysis	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Blood and lymphatic system disorders 39700-Hemolytic uremic syndrome	0.00% 0/206 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.37% 1/269 • Number of events 1 We've excluded the ineligibles from this table.
Cardiac disorders 20000-Cardiac arrest	1.5% 3/206 • Number of events 3 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.37% 1/269 • Number of events 1 We've excluded the ineligibles from this table.
Cardiac disorders 51700-Left ventricular systolic dysfunction	0.00% 0/206 We've excluded the ineligibles from this table.	0.57% 1/176 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Cardiac disorders 63100-Pericardial effusion	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	1.1% 2/176 • Number of events 2 We've excluded the ineligibles from this table.	0.74% 2/269 • Number of events 2 We've excluded the ineligibles from this table.
Cardiac disorders 72700-Right ventricular dysfunction	0.00% 0/206 We've excluded the ineligibles from this table.	0.57% 1/176 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Eye disorders 31900-Eye disorders - Other specify	0.00% 0/206 We've excluded the ineligibles from this table.	0.57% 1/176 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Gastrointestinal disorders 14900-Ascites	0.97% 2/206 • Number of events 2 We've excluded the ineligibles from this table.	1.1% 2/176 • Number of events 2 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Gastrointestinal disorders 35900-Gastric hemorrhage	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Gastrointestinal disorders 36700-Gastrointestinal disorders - Other specify	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Gastrointestinal disorders 36900-Gastrointestinal pain	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Gastrointestinal disorders 53000-Lower gastrointestinal hemorrhage	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.37% 1/269 • Number of events 1 We've excluded the ineligibles from this table.
Gastrointestinal disorders 55600-Mucositis oral	0.97% 2/206 • Number of events 2 We've excluded the ineligibles from this table.	0.57% 1/176 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Gastrointestinal disorders 70100-Rectal hemorrhage	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Gastrointestinal disorders 75700-Small intestinal obstruction	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Gastrointestinal disorders 81900-Typhlitis	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Gastrointestinal disorders 82200-Upper gastrointestinal hemorrhage	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
General disorders 24600-Death NOS	0.00% 0/206 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.74% 2/269 • Number of events 2 We've excluded the ineligibles from this table.
General disorders 37200-General disorders and administration site conditions - Other specify	0.00% 0/206 We've excluded the ineligibles from this table.	0.57% 1/176 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
General disorders 55700-Multi-organ failure	1.9% 4/206 • Number of events 4 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.74% 2/269 • Number of events 2 We've excluded the ineligibles from this table.
Hepatobiliary disorders 40000-Hepatic failure	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.57% 1/176 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Hepatobiliary disorders 40600-Hepatobiliary disorders - Other specify	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Hepatobiliary disorders 66500-Portal hypertension	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Hepatobiliary disorders 66600-Portal vein thrombosis	0.00% 0/206 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.37% 1/269 • Number of events 1 We've excluded the ineligibles from this table.
Infections and infestations 20500-Catheter related infection	0.00% 0/206 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.37% 1/269 • Number of events 1 We've excluded the ineligibles from this table.
Infections and infestations 44800-Infections and infestations - Other specify	1.9% 4/206 • Number of events 4 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.74% 2/269 • Number of events 2 We've excluded the ineligibles from this table.
Infections and infestations 73700-Sepsis	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.57% 1/176 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Injury, poisoning and procedural complications 13800-Aortic injury	0.00% 0/206 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.37% 1/269 • Number of events 1 We've excluded the ineligibles from this table.
Injury, poisoning and procedural complications 45400-Injury to inferior vena cava	0.00% 0/206 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.37% 1/269 • Number of events 1 We've excluded the ineligibles from this table.
Injury, poisoning and procedural complications 47700-Intraoperative renal injury	0.00% 0/206 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.37% 1/269 • Number of events 1 We've excluded the ineligibles from this table.
Investigations 10900-Activated partial thromboplastin time prolonged	0.00% 0/206 We've excluded the ineligibles from this table.	0.57% 1/176 • Number of events 1 We've excluded the ineligibles from this table.	0.37% 1/269 • Number of events 1 We've excluded the ineligibles from this table.
Investigations 11600-Alanine aminotransferase increased	1.5% 3/206 • Number of events 3 We've excluded the ineligibles from this table.	0.57% 1/176 • Number of events 1 We've excluded the ineligibles from this table.	0.74% 2/269 • Number of events 2 We've excluded the ineligibles from this table.
Investigations 15000-Aspartate aminotransferase increased	1.5% 3/206 • Number of events 3 We've excluded the ineligibles from this table.	0.57% 1/176 • Number of events 1 We've excluded the ineligibles from this table.	1.1% 3/269 • Number of events 3 We've excluded the ineligibles from this table.
Investigations 17400-Blood bilirubin increased	1.9% 4/206 • Number of events 4 We've excluded the ineligibles from this table.	0.57% 1/176 • Number of events 1 We've excluded the ineligibles from this table.	0.74% 2/269 • Number of events 2 We've excluded the ineligibles from this table.
Investigations 24100-Creatinine increased	1.5% 3/206 • Number of events 3 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.74% 2/269 • Number of events 2 We've excluded the ineligibles from this table.
Investigations 37500-GGT increased	0.00% 0/206 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.37% 1/269 • Number of events 1 We've excluded the ineligibles from this table.

Other adverse events
Measure	Single HST (CEM) n=206 participants at risk Induction therapy + single myeloablative consolidation	Tandem HST (CEM), Randomly Assigned n=176 participants at risk Induction therapy + tandem myeloablative consolidation	Not Assigned n=269 participants at risk Patients that either failed during Induction therapy or refused randomization
Gastrointestinal disorders 53000-Lower gastrointestinal hemorrhage	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Gastrointestinal disorders 55600-Mucositis oral	9.7% 20/206 • Number of events 21 We've excluded the ineligibles from this table.	9.1% 16/176 • Number of events 16 We've excluded the ineligibles from this table.	2.2% 6/269 • Number of events 6 We've excluded the ineligibles from this table.
Gastrointestinal disorders 57600-Nausea	1.9% 4/206 • Number of events 5 We've excluded the ineligibles from this table.	3.4% 6/176 • Number of events 6 We've excluded the ineligibles from this table.	0.74% 2/269 • Number of events 2 We've excluded the ineligibles from this table.
Gastrointestinal disorders 58900-Obstruction gastric	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Gastrointestinal disorders 59700-Oral pain	0.97% 2/206 • Number of events 2 We've excluded the ineligibles from this table.	2.8% 5/176 • Number of events 5 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Gastrointestinal disorders 75600-Small intestinal mucositis	0.00% 0/206 We've excluded the ineligibles from this table.	0.57% 1/176 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Gastrointestinal disorders 75700-Small intestinal obstruction	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	1.7% 3/176 • Number of events 3 We've excluded the ineligibles from this table.	0.74% 2/269 • Number of events 2 We've excluded the ineligibles from this table.
Gastrointestinal disorders 81900-Typhlitis	0.00% 0/206 We've excluded the ineligibles from this table.	1.1% 2/176 • Number of events 2 We've excluded the ineligibles from this table.	0.37% 1/269 • Number of events 1 We've excluded the ineligibles from this table.
Gastrointestinal disorders 87900-Vomiting	3.4% 7/206 • Number of events 8 We've excluded the ineligibles from this table.	2.3% 4/176 • Number of events 4 We've excluded the ineligibles from this table.	3.0% 8/269 • Number of events 10 We've excluded the ineligibles from this table.
General disorders 28200-Edema face	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
General disorders 33200-Fatigue	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.37% 1/269 • Number of events 1 We've excluded the ineligibles from this table.
General disorders 33900-Fever	1.9% 4/206 • Number of events 4 We've excluded the ineligibles from this table.	0.57% 1/176 • Number of events 1 We've excluded the ineligibles from this table.	0.37% 1/269 • Number of events 1 We've excluded the ineligibles from this table.
General disorders 37200-General disorders and administration site conditions - Other specify	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
General disorders 48700-Irritability	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
General disorders 60600-Pain	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	1.5% 4/269 • Number of events 4 We've excluded the ineligibles from this table.
Hepatobiliary disorders 35500-Gallbladder pain	0.00% 0/206 We've excluded the ineligibles from this table.	0.57% 1/176 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Hepatobiliary disorders 40600-Hepatobiliary disorders - Other specify	0.97% 2/206 • Number of events 2 We've excluded the ineligibles from this table.	1.1% 2/176 • Number of events 2 We've excluded the ineligibles from this table.	0.37% 1/269 • Number of events 1 We've excluded the ineligibles from this table.
Hepatobiliary disorders 66500-Portal hypertension	0.00% 0/206 We've excluded the ineligibles from this table.	0.57% 1/176 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Immune system disorders 12000-Allergic reaction	0.00% 0/206 We've excluded the ineligibles from this table.	0.57% 1/176 • Number of events 2 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Immune system disorders 13100-Anaphylaxis	0.00% 0/206 We've excluded the ineligibles from this table.	1.1% 2/176 • Number of events 2 We've excluded the ineligibles from this table.	0.37% 1/269 • Number of events 1 We've excluded the ineligibles from this table.
Immune system disorders 44700-Immune system disorders - Other specify	0.00% 0/206 We've excluded the ineligibles from this table.	0.57% 1/176 • Number of events 1 We've excluded the ineligibles from this table.	0.37% 1/269 • Number of events 1 We've excluded the ineligibles from this table.
Infections and infestations 13400-Anorectal infection	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.57% 1/176 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Infections and infestations 16800-Bladder infection	0.00% 0/206 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.37% 1/269 • Number of events 1 We've excluded the ineligibles from this table.
Infections and infestations 20500-Catheter related infection	2.9% 6/206 • Number of events 7 We've excluded the ineligibles from this table.	2.8% 5/176 • Number of events 5 We've excluded the ineligibles from this table.	1.5% 4/269 • Number of events 4 We've excluded the ineligibles from this table.
Infections and infestations 25600-Device related infection	0.00% 0/206 We've excluded the ineligibles from this table.	1.1% 2/176 • Number of events 2 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Infections and infestations 29500-Enterocolitis infectious	1.9% 4/206 • Number of events 4 We've excluded the ineligibles from this table.	1.1% 2/176 • Number of events 2 We've excluded the ineligibles from this table.	1.5% 4/269 • Number of events 4 We've excluded the ineligibles from this table.
Infections and infestations 38300-Gum infection	0.00% 0/206 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.37% 1/269 • Number of events 1 We've excluded the ineligibles from this table.
Infections and infestations 44800-Infections and infestations - Other specify	17.5% 36/206 • Number of events 48 We've excluded the ineligibles from this table.	18.2% 32/176 • Number of events 45 We've excluded the ineligibles from this table.	14.5% 39/269 • Number of events 68 We've excluded the ineligibles from this table.
Infections and infestations 53100-Lung infection	1.9% 4/206 • Number of events 4 We've excluded the ineligibles from this table.	0.57% 1/176 • Number of events 1 We've excluded the ineligibles from this table.	0.74% 2/269 • Number of events 2 We've excluded the ineligibles from this table.
Infections and infestations 60100-Otitis media	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Blood and lymphatic system disorders 13200-Anemia	11.2% 23/206 • Number of events 35 We've excluded the ineligibles from this table.	12.5% 22/176 • Number of events 37 We've excluded the ineligibles from this table.	12.3% 33/269 • Number of events 42 We've excluded the ineligibles from this table.
Blood and lymphatic system disorders 17200-Blood and lymphatic system disorders - Other specify	0.00% 0/206 We've excluded the ineligibles from this table.	0.57% 1/176 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Blood and lymphatic system disorders 25800-Disseminated intravascular coagulation	0.97% 2/206 • Number of events 2 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.37% 1/269 • Number of events 1 We've excluded the ineligibles from this table.
Blood and lymphatic system disorders 33300-Febrile neutropenia	15.5% 32/206 • Number of events 46 We've excluded the ineligibles from this table.	18.2% 32/176 • Number of events 41 We've excluded the ineligibles from this table.	17.1% 46/269 • Number of events 53 We've excluded the ineligibles from this table.
Cardiac disorders 20000-Cardiac arrest	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.37% 1/269 • Number of events 1 We've excluded the ineligibles from this table.
Cardiac disorders 20100-Cardiac disorders - Other specify	0.00% 0/206 We've excluded the ineligibles from this table.	0.57% 1/176 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Cardiac disorders 39000-Heart failure	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Cardiac disorders 63100-Pericardial effusion	0.00% 0/206 We've excluded the ineligibles from this table.	0.57% 1/176 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Cardiac disorders 72700-Right ventricular dysfunction	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.
Ear and labyrinth disorders 27900-Ear and labyrinth disorders - Other specify	0.49% 1/206 • Number of events 1 We've excluded the ineligibles from this table.	0.00% 0/176 We've excluded the ineligibles from this table.	0.00% 0/269 We've excluded the ineligibles from this table.