Trial Outcomes & Findings for HLA-Compatible Related or Unrelated Donors With CD34+ Enriched, T-cell Depleted Peripheral Blood Stem Cells Isolated by the CliniMACS System in the Treatment of Patients With Hematologic Malignancies (NCT NCT01119066)

NCT ID: NCT01119066

Last Updated: 2022-08-05

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

422 participants

Primary outcome timeframe

3 years

Results posted on

2022-08-05

Participant Flow

2 patients received 2 separate transplants on each Arm A and C

Unit of analysis: Additional Transplant

Participant milestones

Participant milestones
Measure	Total Body Irradiation, Thiotepa and Cyclophosphamide Hyperfractionated total body irradiation to a dose of 1375-1500 cGy (depending on age, stage of disease and requirement of general anesthesia) with lung shielding) Thiotepa (5 mg/kg/day x 2 or 10 mg/kg/day x 1) Cyclophosphamide (60 mg/kg/day x 2) (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated) total body irradiation: dose of 1375-1500 cGy Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Cyclophosphamide: 60 mg/ kg/day x 2 (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated). (CliniMACS) T-cell depleted PBSC Transplant	Busulfan, Melphalan and Fludarabine Busulfan (0.8 mg/kg every 6 hours x 10 or 12 doses), (depending on disease) with dose modified according to pharmacokinetics Melphalan (70mg/m2/day x 2 ) Fludarabine (25mg/m2/ day x 5) Busulfan: 0.8 mg/kg every 6 hours x 10 or 12 doses (depending on disease) with dose modified according to pharmacokinetics Melphalan: 70mg/m2/day x 2 Fludarabine: 25mg/m2/ day x 5 (CliniMACS) T-cell depleted PBSC Transplant	Clofarabine, Melphalan and Thiotepa Clofarabine (20mg/m2/ day x 5) (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval), Melphalan (70 mg/m2/day x 2) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1) Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Melphalan: 70mg/m2/day x 2 Clofarabine: 20mg/m2/ day x 5 (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval) (CliniMACS) T-cell depleted PBSC Transplant	Melphalan, Fludarabine and Thiotepa Melphalan (70 mg/m2/day x 2) Fludarabine (25mg/m2/ day x 5 ) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1) Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Melphalan: 70mg/m2/day x 2 (CliniMACS) T-cell depleted PBSC Transplant
Overall Study STARTED	132 1	227 0	52 1	11 0
Overall Study COMPLETED	125 1	213 0	52 1	11 0
Overall Study NOT COMPLETED	7 0	14 0	0 0	0 0

Reasons for withdrawal

Reasons for withdrawal
Measure	Total Body Irradiation, Thiotepa and Cyclophosphamide Hyperfractionated total body irradiation to a dose of 1375-1500 cGy (depending on age, stage of disease and requirement of general anesthesia) with lung shielding) Thiotepa (5 mg/kg/day x 2 or 10 mg/kg/day x 1) Cyclophosphamide (60 mg/kg/day x 2) (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated) total body irradiation: dose of 1375-1500 cGy Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Cyclophosphamide: 60 mg/ kg/day x 2 (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated). (CliniMACS) T-cell depleted PBSC Transplant	Busulfan, Melphalan and Fludarabine Busulfan (0.8 mg/kg every 6 hours x 10 or 12 doses), (depending on disease) with dose modified according to pharmacokinetics Melphalan (70mg/m2/day x 2 ) Fludarabine (25mg/m2/ day x 5) Busulfan: 0.8 mg/kg every 6 hours x 10 or 12 doses (depending on disease) with dose modified according to pharmacokinetics Melphalan: 70mg/m2/day x 2 Fludarabine: 25mg/m2/ day x 5 (CliniMACS) T-cell depleted PBSC Transplant
Overall Study Withdrawal by Subject	4	6
Overall Study Concern regarding adequacy of transplant cell dose	2	1
Overall Study Relapse identified before transplant	0	4
Overall Study Intercurrent medication condition rendered patient ineligible	0	3

Baseline Characteristics

HLA-Compatible Related or Unrelated Donors With CD34+ Enriched, T-cell Depleted Peripheral Blood Stem Cells Isolated by the CliniMACS System in the Treatment of Patients With Hematologic Malignancies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Total Body Irradiation, Thiotepa and Cyclophosphamide n=125 Participants Hyperfractionated total body irradiation to a dose of 1375-1500 cGy (depending on age, stage of disease and requirement of general anesthesia) with lung shielding) Thiotepa (5 mg/kg/day x 2 or 10 mg/kg/day x 1) Cyclophosphamide (60 mg/kg/day x 2) (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated) total body irradiation: dose of 1375-1500 cGy Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Cyclophosphamide: 60 mg/ kg/day x 2 (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated). (CliniMACS) T-cell depleted PBSC Transplant	Busulfan, Melphalan and Fludarabine n=213 Participants Busulfan (0.8 mg/kg every 6 hours x 10 or 12 doses), (depending on disease) with dose modified according to pharmacokinetics Melphalan (70mg/m2/day x 2 ) Fludarabine (25mg/m2/ day x 5) Busulfan: 0.8 mg/kg every 6 hours x 10 or 12 doses (depending on disease) with dose modified according to pharmacokinetics Melphalan: 70mg/m2/day x 2 Fludarabine: 25mg/m2/ day x 5 (CliniMACS) T-cell depleted PBSC Transplant	Clofarabine, Melphalan and Thiotepa n=52 Participants Clofarabine (20mg/m2/ day x 5) (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval), Melphalan (70 mg/m2/day x 2) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1) Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Melphalan: 70mg/m2/day x 2 Clofarabine: 20mg/m2/ day x 5 (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval) (CliniMACS) T-cell depleted PBSC Transplant	Melphalan, Fludarabine and Thiotepa n=11 Participants Melphalan (70 mg/m2/day x 2) Fludarabine (25mg/m2/ day x 5 ) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1) Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Melphalan: 70mg/m2/day x 2 (CliniMACS) T-cell depleted PBSC Transplant	Total n=401 Participants Total of all reporting groups
Age, Continuous	30.3 years n=5 Participants	57.6 years n=7 Participants	28.1 years n=5 Participants	10 years n=4 Participants	48 years n=21 Participants
Sex: Female, Male Female	63 Participants n=5 Participants	91 Participants n=7 Participants	21 Participants n=5 Participants	5 Participants n=4 Participants	180 Participants n=21 Participants
Sex: Female, Male Male	62 Participants n=5 Participants	122 Participants n=7 Participants	31 Participants n=5 Participants	6 Participants n=4 Participants	221 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	18 Participants n=5 Participants	10 Participants n=7 Participants	6 Participants n=5 Participants	4 Participants n=4 Participants	38 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	64 Participants n=5 Participants	145 Participants n=7 Participants	30 Participants n=5 Participants	5 Participants n=4 Participants	244 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	43 Participants n=5 Participants	58 Participants n=7 Participants	16 Participants n=5 Participants	2 Participants n=4 Participants	119 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	9 Participants n=5 Participants	13 Participants n=7 Participants	5 Participants n=5 Participants	2 Participants n=4 Participants	29 Participants n=21 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	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	13 Participants n=5 Participants	17 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	33 Participants n=21 Participants
Race (NIH/OMB) White	94 Participants n=5 Participants	176 Participants n=7 Participants	41 Participants n=5 Participants	6 Participants n=4 Participants	317 Participants n=21 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	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants	7 Participants n=7 Participants	5 Participants n=5 Participants	1 Participants n=4 Participants	21 Participants n=21 Participants
Region of Enrollment United States	125 Participants n=5 Participants	213 Participants n=7 Participants	52 Participants n=5 Participants	11 Participants n=4 Participants	401 Participants n=21 Participants

PRIMARY outcome

Timeframe: 3 years

Population: Please note 13 participants were not evaluated in the data set as they received a second or third HCT on protocol.

Outcome measures

Outcome measures
Measure	Busulfan, Melphalan and Fludarabine n=210 Participants Busulfan (0.8 mg/kg every 6 hours x 10 or 12 doses), (depending on disease) with dose modified according to pharmacokinetics Melphalan (70mg/m2/day x 2 ) Fludarabine (25mg/m2/ day x 5) Busulfan: 0.8 mg/kg every 6 hours x 10 or 12 doses (depending on disease) with dose modified according to pharmacokinetics Melphalan: 70mg/m2/day x 2 Fludarabine: 25mg/m2/ day x 5 (CliniMACS) T-cell depleted PBSC Transplant	Clofarabine, Melphalan and Thiotepa n=47 Participants Clofarabine (20mg/m2/ day x 5) (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval), Melphalan (70 mg/m2/day x 2) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1) Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Melphalan: 70mg/m2/day x 2 Clofarabine: 20mg/m2/ day x 5 (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval) (CliniMACS) T-cell depleted PBSC Transplant	Melphalan, Fludarabine and Thiotepa n=11 Participants Melphalan (70 mg/m2/day x 2) Fludarabine (25mg/m2/ day x 5 ) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1) Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Melphalan: 70mg/m2/day x 2 (CliniMACS) T-cell depleted PBSC Transplant	Total Body Irradiation, Thiotepa and Cyclophosphamide n=120 Participants Hyperfractionated total body irradiation to a dose of 1375-1500 cGy (depending on age, stage of disease and requirement of general anesthesia) with lung shielding) Thiotepa (5 mg/kg/day x 2 or 10 mg/kg/day x 1) Cyclophosphamide (60 mg/kg/day x 2) (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated) total body irradiation: dose of 1375-1500 cGy Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Cyclophosphamide: 60 mg/ kg/day x 2 (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated). (CliniMACS) T-cell depleted PBSC Transplant
The Incidence of Durable Hematopoietic Engraftment for T-cell Depleted Transplants Fractionated by the CliniMACS System Administered After Each of the Four Disease Targeted Cytoreduction Regimens. Engrafted	205 Participants	45 Participants	10 Participants	118 Participants
The Incidence of Durable Hematopoietic Engraftment for T-cell Depleted Transplants Fractionated by the CliniMACS System Administered After Each of the Four Disease Targeted Cytoreduction Regimens. Primary Graft Failure	0 Participants	0 Participants	0 Participants	0 Participants
The Incidence of Durable Hematopoietic Engraftment for T-cell Depleted Transplants Fractionated by the CliniMACS System Administered After Each of the Four Disease Targeted Cytoreduction Regimens. Late graft failure	5 Participants	2 Participants	1 Participants	1 Participants
The Incidence of Durable Hematopoietic Engraftment for T-cell Depleted Transplants Fractionated by the CliniMACS System Administered After Each of the Four Disease Targeted Cytoreduction Regimens. Not Evaluable Engraftment	0 Participants	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: 3 years

Standard BMT-CTN and IBMTR systems clinical criteria as defined by Rowlings, et al will be used to establish and grade acute GvHD. Chronic GvHD will be diagnosed and graded according to the criteria of Sullivan (CIBMTR).

Outcome measures

Outcome measures
Measure	Busulfan, Melphalan and Fludarabine n=65 Participants Busulfan (0.8 mg/kg every 6 hours x 10 or 12 doses), (depending on disease) with dose modified according to pharmacokinetics Melphalan (70mg/m2/day x 2 ) Fludarabine (25mg/m2/ day x 5) Busulfan: 0.8 mg/kg every 6 hours x 10 or 12 doses (depending on disease) with dose modified according to pharmacokinetics Melphalan: 70mg/m2/day x 2 Fludarabine: 25mg/m2/ day x 5 (CliniMACS) T-cell depleted PBSC Transplant	Clofarabine, Melphalan and Thiotepa n=12 Participants Clofarabine (20mg/m2/ day x 5) (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval), Melphalan (70 mg/m2/day x 2) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1) Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Melphalan: 70mg/m2/day x 2 Clofarabine: 20mg/m2/ day x 5 (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval) (CliniMACS) T-cell depleted PBSC Transplant	Melphalan, Fludarabine and Thiotepa n=3 Participants Melphalan (70 mg/m2/day x 2) Fludarabine (25mg/m2/ day x 5 ) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1) Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Melphalan: 70mg/m2/day x 2 (CliniMACS) T-cell depleted PBSC Transplant	Total Body Irradiation, Thiotepa and Cyclophosphamide n=44 Participants Hyperfractionated total body irradiation to a dose of 1375-1500 cGy (depending on age, stage of disease and requirement of general anesthesia) with lung shielding) Thiotepa (5 mg/kg/day x 2 or 10 mg/kg/day x 1) Cyclophosphamide (60 mg/kg/day x 2) (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated) total body irradiation: dose of 1375-1500 cGy Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Cyclophosphamide: 60 mg/ kg/day x 2 (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated). (CliniMACS) T-cell depleted PBSC Transplant
Number of Participants With Acute and Chronic GVHD Following T-cell Depleted, CD34+ Progenitor Cell Enriched Transplants Fractionated by the CliniMACS System. aGVHD II-IV	60 participants	10 participants	2 participants	34 participants
Number of Participants With Acute and Chronic GVHD Following T-cell Depleted, CD34+ Progenitor Cell Enriched Transplants Fractionated by the CliniMACS System. cGVHD, Limited	4 participants	1 participants	0 participants	2 participants
Number of Participants With Acute and Chronic GVHD Following T-cell Depleted, CD34+ Progenitor Cell Enriched Transplants Fractionated by the CliniMACS System. cGVHD, Extensive	1 participants	1 participants	1 participants	8 participants

PRIMARY outcome

Timeframe: 3 years

Population: Please note 13 participants were not evaluated in the data set as they received a second or third HCT on protocol.

Outcome measures

Outcome measures
Measure	Busulfan, Melphalan and Fludarabine n=210 Participants Busulfan (0.8 mg/kg every 6 hours x 10 or 12 doses), (depending on disease) with dose modified according to pharmacokinetics Melphalan (70mg/m2/day x 2 ) Fludarabine (25mg/m2/ day x 5) Busulfan: 0.8 mg/kg every 6 hours x 10 or 12 doses (depending on disease) with dose modified according to pharmacokinetics Melphalan: 70mg/m2/day x 2 Fludarabine: 25mg/m2/ day x 5 (CliniMACS) T-cell depleted PBSC Transplant	Clofarabine, Melphalan and Thiotepa n=47 Participants Clofarabine (20mg/m2/ day x 5) (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval), Melphalan (70 mg/m2/day x 2) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1) Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Melphalan: 70mg/m2/day x 2 Clofarabine: 20mg/m2/ day x 5 (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval) (CliniMACS) T-cell depleted PBSC Transplant	Melphalan, Fludarabine and Thiotepa n=11 Participants Melphalan (70 mg/m2/day x 2) Fludarabine (25mg/m2/ day x 5 ) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1) Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Melphalan: 70mg/m2/day x 2 (CliniMACS) T-cell depleted PBSC Transplant	Total Body Irradiation, Thiotepa and Cyclophosphamide n=120 Participants Hyperfractionated total body irradiation to a dose of 1375-1500 cGy (depending on age, stage of disease and requirement of general anesthesia) with lung shielding) Thiotepa (5 mg/kg/day x 2 or 10 mg/kg/day x 1) Cyclophosphamide (60 mg/kg/day x 2) (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated) total body irradiation: dose of 1375-1500 cGy Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Cyclophosphamide: 60 mg/ kg/day x 2 (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated). (CliniMACS) T-cell depleted PBSC Transplant
Incidence of Non-relapse Mortality (Transplant-related Mortality) Following Each Cytoreduction Regimen and a Transplant Fractionated by the CliniMACS System. Alive	145 Participants	30 Participants	8 Participants	81 Participants
Incidence of Non-relapse Mortality (Transplant-related Mortality) Following Each Cytoreduction Regimen and a Transplant Fractionated by the CliniMACS System. Dead (not non-relapse mortality)	24 Participants	3 Participants	0 Participants	23 Participants
Incidence of Non-relapse Mortality (Transplant-related Mortality) Following Each Cytoreduction Regimen and a Transplant Fractionated by the CliniMACS System. Dead (non-relapse mortality)	41 Participants	14 Participants	3 Participants	16 Participants

PRIMARY outcome

Timeframe: at 6 months post transplant

Population: 2 patients received 2 separate transplants on each Arm A and C

Outcome measures

Outcome measures
Measure	Busulfan, Melphalan and Fludarabine n=213 Participants Busulfan (0.8 mg/kg every 6 hours x 10 or 12 doses), (depending on disease) with dose modified according to pharmacokinetics Melphalan (70mg/m2/day x 2 ) Fludarabine (25mg/m2/ day x 5) Busulfan: 0.8 mg/kg every 6 hours x 10 or 12 doses (depending on disease) with dose modified according to pharmacokinetics Melphalan: 70mg/m2/day x 2 Fludarabine: 25mg/m2/ day x 5 (CliniMACS) T-cell depleted PBSC Transplant	Clofarabine, Melphalan and Thiotepa n=52 Participants Clofarabine (20mg/m2/ day x 5) (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval), Melphalan (70 mg/m2/day x 2) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1) Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Melphalan: 70mg/m2/day x 2 Clofarabine: 20mg/m2/ day x 5 (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval) (CliniMACS) T-cell depleted PBSC Transplant	Melphalan, Fludarabine and Thiotepa n=11 Participants Melphalan (70 mg/m2/day x 2) Fludarabine (25mg/m2/ day x 5 ) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1) Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Melphalan: 70mg/m2/day x 2 (CliniMACS) T-cell depleted PBSC Transplant	Total Body Irradiation, Thiotepa and Cyclophosphamide n=125 Participants Hyperfractionated total body irradiation to a dose of 1375-1500 cGy (depending on age, stage of disease and requirement of general anesthesia) with lung shielding) Thiotepa (5 mg/kg/day x 2 or 10 mg/kg/day x 1) Cyclophosphamide (60 mg/kg/day x 2) (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated) total body irradiation: dose of 1375-1500 cGy Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Cyclophosphamide: 60 mg/ kg/day x 2 (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated). (CliniMACS) T-cell depleted PBSC Transplant
Survival and Disease-free Survival (DFS) Survival	92.4 percentage of participants	87.2 percentage of participants	90.9 percentage of participants	93.3 percentage of participants
Survival and Disease-free Survival (DFS) Disease Free Survival	89.0 percentage of participants	85.1 percentage of participants	90.9 percentage of participants	82.5 percentage of participants

PRIMARY outcome

Timeframe: 1 year post transplant

Population: 2 patients received 2 separate transplants on each Arm A and C

Outcome measures

Outcome measures
Measure	Busulfan, Melphalan and Fludarabine n=213 Participants Busulfan (0.8 mg/kg every 6 hours x 10 or 12 doses), (depending on disease) with dose modified according to pharmacokinetics Melphalan (70mg/m2/day x 2 ) Fludarabine (25mg/m2/ day x 5) Busulfan: 0.8 mg/kg every 6 hours x 10 or 12 doses (depending on disease) with dose modified according to pharmacokinetics Melphalan: 70mg/m2/day x 2 Fludarabine: 25mg/m2/ day x 5 (CliniMACS) T-cell depleted PBSC Transplant	Clofarabine, Melphalan and Thiotepa n=52 Participants Clofarabine (20mg/m2/ day x 5) (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval), Melphalan (70 mg/m2/day x 2) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1) Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Melphalan: 70mg/m2/day x 2 Clofarabine: 20mg/m2/ day x 5 (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval) (CliniMACS) T-cell depleted PBSC Transplant	Melphalan, Fludarabine and Thiotepa n=11 Participants Melphalan (70 mg/m2/day x 2) Fludarabine (25mg/m2/ day x 5 ) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1) Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Melphalan: 70mg/m2/day x 2 (CliniMACS) T-cell depleted PBSC Transplant	Total Body Irradiation, Thiotepa and Cyclophosphamide n=125 Participants Hyperfractionated total body irradiation to a dose of 1375-1500 cGy (depending on age, stage of disease and requirement of general anesthesia) with lung shielding) Thiotepa (5 mg/kg/day x 2 or 10 mg/kg/day x 1) Cyclophosphamide (60 mg/kg/day x 2) (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated) total body irradiation: dose of 1375-1500 cGy Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Cyclophosphamide: 60 mg/ kg/day x 2 (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated). (CliniMACS) T-cell depleted PBSC Transplant
Survival and Disease-free Survival (DFS) Survival	83.8 % of pts at 1 year post transplant	85.1 % of pts at 1 year post transplant	81.8 % of pts at 1 year post transplant	80.8 % of pts at 1 year post transplant
Survival and Disease-free Survival (DFS) Disease free survival	73.7 % of pts at 1 year post transplant	83.0 % of pts at 1 year post transplant	72.7 % of pts at 1 year post transplant	68.3 % of pts at 1 year post transplant

PRIMARY outcome

Timeframe: 2 years post transplant

Population: 2 patients received 2 separate transplants on each Arm A and C

Outcome measures

Outcome measures
Measure	Busulfan, Melphalan and Fludarabine n=213 Participants Busulfan (0.8 mg/kg every 6 hours x 10 or 12 doses), (depending on disease) with dose modified according to pharmacokinetics Melphalan (70mg/m2/day x 2 ) Fludarabine (25mg/m2/ day x 5) Busulfan: 0.8 mg/kg every 6 hours x 10 or 12 doses (depending on disease) with dose modified according to pharmacokinetics Melphalan: 70mg/m2/day x 2 Fludarabine: 25mg/m2/ day x 5 (CliniMACS) T-cell depleted PBSC Transplant	Clofarabine, Melphalan and Thiotepa n=52 Participants Clofarabine (20mg/m2/ day x 5) (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval), Melphalan (70 mg/m2/day x 2) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1) Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Melphalan: 70mg/m2/day x 2 Clofarabine: 20mg/m2/ day x 5 (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval) (CliniMACS) T-cell depleted PBSC Transplant	Melphalan, Fludarabine and Thiotepa n=11 Participants Melphalan (70 mg/m2/day x 2) Fludarabine (25mg/m2/ day x 5 ) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1) Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Melphalan: 70mg/m2/day x 2 (CliniMACS) T-cell depleted PBSC Transplant	Total Body Irradiation, Thiotepa and Cyclophosphamide n=125 Participants Hyperfractionated total body irradiation to a dose of 1375-1500 cGy (depending on age, stage of disease and requirement of general anesthesia) with lung shielding) Thiotepa (5 mg/kg/day x 2 or 10 mg/kg/day x 1) Cyclophosphamide (60 mg/kg/day x 2) (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated) total body irradiation: dose of 1375-1500 cGy Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Cyclophosphamide: 60 mg/ kg/day x 2 (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated). (CliniMACS) T-cell depleted PBSC Transplant
Survival and Disease-free Survival (DFS) Survival	72.1 % of pts at 2 years	63.8 % of pts at 2 years	71.6 % of pts at 2 years	68.7 % of pts at 2 years
Survival and Disease-free Survival (DFS) Disease Free Survival	62.1 % of pts at 2 years	59.6 % of pts at 2 years	62.3 % of pts at 2 years	58.9 % of pts at 2 years

SECONDARY outcome

Timeframe: Up to 3 years

Population: 2 patients received 2 separate transplants on each Arm A and C. Please note 13 participants were not evaluated in the data set as they received a second or third HCT on protocol.

Outcome measures

Outcome measures
Measure	Busulfan, Melphalan and Fludarabine n=210 Participants Busulfan (0.8 mg/kg every 6 hours x 10 or 12 doses), (depending on disease) with dose modified according to pharmacokinetics Melphalan (70mg/m2/day x 2 ) Fludarabine (25mg/m2/ day x 5) Busulfan: 0.8 mg/kg every 6 hours x 10 or 12 doses (depending on disease) with dose modified according to pharmacokinetics Melphalan: 70mg/m2/day x 2 Fludarabine: 25mg/m2/ day x 5 (CliniMACS) T-cell depleted PBSC Transplant	Clofarabine, Melphalan and Thiotepa n=47 Participants Clofarabine (20mg/m2/ day x 5) (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval), Melphalan (70 mg/m2/day x 2) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1) Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Melphalan: 70mg/m2/day x 2 Clofarabine: 20mg/m2/ day x 5 (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval) (CliniMACS) T-cell depleted PBSC Transplant	Melphalan, Fludarabine and Thiotepa n=11 Participants Melphalan (70 mg/m2/day x 2) Fludarabine (25mg/m2/ day x 5 ) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1) Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Melphalan: 70mg/m2/day x 2 (CliniMACS) T-cell depleted PBSC Transplant	Total Body Irradiation, Thiotepa and Cyclophosphamide n=120 Participants Hyperfractionated total body irradiation to a dose of 1375-1500 cGy (depending on age, stage of disease and requirement of general anesthesia) with lung shielding) Thiotepa (5 mg/kg/day x 2 or 10 mg/kg/day x 1) Cyclophosphamide (60 mg/kg/day x 2) (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated) total body irradiation: dose of 1375-1500 cGy Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Cyclophosphamide: 60 mg/ kg/day x 2 (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated). (CliniMACS) T-cell depleted PBSC Transplant
Proportion of Patients Receiving Optimal CD3+ (<1x10^5/kg) Cell Doses the Proportion of Patients Receiving CD3+ T-cell Doses > 1x10^5/kg. CD3 Optimal	210 Participants	47 Participants	11 Participants	120 Participants
Proportion of Patients Receiving Optimal CD3+ (<1x10^5/kg) Cell Doses the Proportion of Patients Receiving CD3+ T-cell Doses > 1x10^5/kg. CD3 Suboptimal	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 3 years

Population: Please note 13 participants were not evaluated in the data set as they received a second or third HCT on protocol.

Outcome measures

Outcome measures
Measure	Busulfan, Melphalan and Fludarabine n=210 Participants Busulfan (0.8 mg/kg every 6 hours x 10 or 12 doses), (depending on disease) with dose modified according to pharmacokinetics Melphalan (70mg/m2/day x 2 ) Fludarabine (25mg/m2/ day x 5) Busulfan: 0.8 mg/kg every 6 hours x 10 or 12 doses (depending on disease) with dose modified according to pharmacokinetics Melphalan: 70mg/m2/day x 2 Fludarabine: 25mg/m2/ day x 5 (CliniMACS) T-cell depleted PBSC Transplant	Clofarabine, Melphalan and Thiotepa n=47 Participants Clofarabine (20mg/m2/ day x 5) (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval), Melphalan (70 mg/m2/day x 2) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1) Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Melphalan: 70mg/m2/day x 2 Clofarabine: 20mg/m2/ day x 5 (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval) (CliniMACS) T-cell depleted PBSC Transplant	Melphalan, Fludarabine and Thiotepa n=11 Participants Melphalan (70 mg/m2/day x 2) Fludarabine (25mg/m2/ day x 5 ) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1) Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Melphalan: 70mg/m2/day x 2 (CliniMACS) T-cell depleted PBSC Transplant	Total Body Irradiation, Thiotepa and Cyclophosphamide n=120 Participants Hyperfractionated total body irradiation to a dose of 1375-1500 cGy (depending on age, stage of disease and requirement of general anesthesia) with lung shielding) Thiotepa (5 mg/kg/day x 2 or 10 mg/kg/day x 1) Cyclophosphamide (60 mg/kg/day x 2) (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated) total body irradiation: dose of 1375-1500 cGy Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Cyclophosphamide: 60 mg/ kg/day x 2 (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated). (CliniMACS) T-cell depleted PBSC Transplant
Proportion of Patients Receiving Optimal CD34+ (> 5x10^6/kg) Cell Doses the Proportion Recurring Suboptimal Doses (< 2x10^6/kg) CD34+ Cells Suboptimal	1 Participants	0 Participants	0 Participants	0 Participants
Proportion of Patients Receiving Optimal CD34+ (> 5x10^6/kg) Cell Doses the Proportion Recurring Suboptimal Doses (< 2x10^6/kg) CD34+ Cells Optimal	169 Participants	39 Participants	11 Participants	105 Participants
Proportion of Patients Receiving Optimal CD34+ (> 5x10^6/kg) Cell Doses the Proportion Recurring Suboptimal Doses (< 2x10^6/kg) CD34+ Cells None	40 Participants	8 Participants	0 Participants	15 Participants

SECONDARY outcome

Timeframe: 3 years

Population: Please note 13 participants were not evaluated in the data set as they received a second or third HCT on protocol.

Outcome measures

Outcome measures
Measure	Busulfan, Melphalan and Fludarabine n=209 Participants Busulfan (0.8 mg/kg every 6 hours x 10 or 12 doses), (depending on disease) with dose modified according to pharmacokinetics Melphalan (70mg/m2/day x 2 ) Fludarabine (25mg/m2/ day x 5) Busulfan: 0.8 mg/kg every 6 hours x 10 or 12 doses (depending on disease) with dose modified according to pharmacokinetics Melphalan: 70mg/m2/day x 2 Fludarabine: 25mg/m2/ day x 5 (CliniMACS) T-cell depleted PBSC Transplant	Clofarabine, Melphalan and Thiotepa n=47 Participants Clofarabine (20mg/m2/ day x 5) (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval), Melphalan (70 mg/m2/day x 2) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1) Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Melphalan: 70mg/m2/day x 2 Clofarabine: 20mg/m2/ day x 5 (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval) (CliniMACS) T-cell depleted PBSC Transplant	Melphalan, Fludarabine and Thiotepa n=11 Participants Melphalan (70 mg/m2/day x 2) Fludarabine (25mg/m2/ day x 5 ) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1) Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Melphalan: 70mg/m2/day x 2 (CliniMACS) T-cell depleted PBSC Transplant	Total Body Irradiation, Thiotepa and Cyclophosphamide n=120 Participants Hyperfractionated total body irradiation to a dose of 1375-1500 cGy (depending on age, stage of disease and requirement of general anesthesia) with lung shielding) Thiotepa (5 mg/kg/day x 2 or 10 mg/kg/day x 1) Cyclophosphamide (60 mg/kg/day x 2) (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated) total body irradiation: dose of 1375-1500 cGy Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Cyclophosphamide: 60 mg/ kg/day x 2 (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated). (CliniMACS) T-cell depleted PBSC Transplant
Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment Optimal (> 5x106/kg), Late Graft Failure	5 Participants	1 Participants	0 Participants	1 Participants
Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment Optimal (> 5x106/kg), Not Evaluable	0 Participants	0 Participants	0 Participants	1 Participants
Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment Suboptimal(< 2x106/kg), Late Graft Failure	0 Participants	0 Participants	0 Participants	0 Participants
Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment Suboptimal(< 2x106/kg), Not Evaluable	0 Participants	0 Participants	0 Participants	0 Participants
Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment Other(2-5X106/kg), Not Evaluable	0 Participants	0 Participants	0 Participants	0 Participants
Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment Optimal (> 5x106/kg), Engrafted	163 Participants	38 Participants	11 Participants	103 Participants
Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment Suboptimal(< 2x106/kg), Engrafted	1 Participants	0 Participants	0 Participants	0 Participants
Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment Other(2-5X106/kg), Engrafted	40 Participants	7 Participants	0 Participants	15 Participants
Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment Other(2-5X106/kg), Late Graft Failure	0 Participants	1 Participants	0 Participants	0 Participants

Adverse Events

Total Body Irradiation, Thiotepa and Cyclophosphamide

Serious events: 13 serious events

Other events: 16 other events

Deaths: 42 deaths

Busulfan, Melphalan and Fludarabine

Serious events: 30 serious events

Other events: 31 other events

Deaths: 71 deaths

Clofarabine, Melphalan and Thiotepa

Serious events: 9 serious events

Other events: 9 other events

Deaths: 18 deaths

Melphalan, Fludarabine and Thiotepa

Serious events: 3 serious events

Other events: 3 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Richard O'Reilly, MD

Memorial Sloan Kettering Cancer Center

Phone: 646-888-2157

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Total Body Irradiation, Thiotepa and Cyclophosphamide n=125 participants at risk Hyperfractionated total body irradiation to a dose of 1375-1500 cGy (depending on age, stage of disease and requirement of general anesthesia) with lung shielding) Thiotepa (5 mg/kg/day x 2 or 10 mg/kg/day x 1) Cyclophosphamide (60 mg/kg/day x 2) (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated) total body irradiation: dose of 1375-1500 cGy Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Cyclophosphamide: 60 mg/ kg/day x 2 (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated). (CliniMACS) T-cell depleted PBSC Transplant	Busulfan, Melphalan and Fludarabine n=213 participants at risk Busulfan (0.8 mg/kg every 6 hours x 10 or 12 doses), (depending on disease) with dose modified according to pharmacokinetics Melphalan (70mg/m2/day x 2 ) Fludarabine (25mg/m2/ day x 5) Busulfan: 0.8 mg/kg every 6 hours x 10 or 12 doses (depending on disease) with dose modified according to pharmacokinetics Melphalan: 70mg/m2/day x 2 Fludarabine: 25mg/m2/ day x 5 (CliniMACS) T-cell depleted PBSC Transplant	Clofarabine, Melphalan and Thiotepa n=52 participants at risk Clofarabine (20mg/m2/ day x 5) (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval), Melphalan (70 mg/m2/day x 2) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1) Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Melphalan: 70mg/m2/day x 2 Clofarabine: 20mg/m2/ day x 5 (or, for children \<18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval) (CliniMACS) T-cell depleted PBSC Transplant	Melphalan, Fludarabine and Thiotepa n=11 participants at risk Melphalan (70 mg/m2/day x 2) Fludarabine (25mg/m2/ day x 5 ) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1) Thiotepa: 5 mg/kg/day x 2 or 10 mg/kg/day x 1 Melphalan: 70mg/m2/day x 2 (CliniMACS) T-cell depleted PBSC Transplant
Metabolism and nutrition disorders Acidosis	0.00% 0/125 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.47% 1/213 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/52 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/11 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol
Renal and urinary disorders Acute kidney injury	0.00% 0/125 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.47% 1/213 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	1.9% 1/52 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/11 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol
Infections and infestations Appendicitis	0.00% 0/125 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.47% 1/213 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/52 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/11 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol
Cardiac disorders Cardiac arrest	0.00% 0/125 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	1.4% 3/213 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/52 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/11 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol
General disorders Death NOS	6.4% 8/125 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	5.6% 12/213 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	13.5% 7/52 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	18.2% 2/11 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/125 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/213 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	1.9% 1/52 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/11 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol
General disorders Gen disorders & admin site conditions Other, spec	0.00% 0/125 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.47% 1/213 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/52 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/11 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol
Hepatobiliary disorders Hepatobiliary disorders - Other, specify	0.00% 0/125 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.47% 1/213 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/52 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/11 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol
Vascular disorders Hypotension	0.00% 0/125 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/213 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	1.9% 1/52 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/11 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol
Respiratory, thoracic and mediastinal disorders Hypoxia	4.0% 5/125 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	1.9% 4/213 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	1.9% 1/52 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/11 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol
Infections and infestations Infections and infestations - Other, specify	0.00% 0/125 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	1.4% 3/213 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/52 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	9.1% 1/11 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol
Infections and infestations Meningitis	0.00% 0/125 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.47% 1/213 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/52 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/11 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol
Investigations Neutrophil count decreased	0.00% 0/125 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.47% 1/213 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	1.9% 1/52 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/11 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol
Cardiac disorders Pericardial tamponade	0.80% 1/125 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/213 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/52 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/11 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol
Investigations Platelet count decreased	0.00% 0/125 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.47% 1/213 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/52 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/11 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol
Psychiatric disorders Psychiatric disorders - Other, specify	0.00% 0/125 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.47% 1/213 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/52 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/11 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.80% 1/125 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	1.9% 4/213 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	1.9% 1/52 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/11 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol
Infections and infestations Sepsis	1.6% 2/125 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	1.9% 4/213 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	3.8% 2/52 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/11 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol
Skin and subcutaneous tissue disorders Skin & subcutaneous tissue disorders Other, spec	0.80% 1/125 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/213 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/52 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/11 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol
Gastrointestinal disorders Vomiting	0.80% 1/125 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/213 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/52 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol	0.00% 0/11 • Up to 3 years Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol