HLA-Compatible Related or Unrelated Donors With CD34+ Enr... | NCT01119066

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Total Body Irradiation, Thiotepa and Cyclophosphamide	Experimental	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)	Radiation: total body irradiation Drug: Thiotepa Drug: Cyclophosphamide Procedure: (CliniMACS) T-cell depleted PBSC Transplant
Busulfan, Melphalan and Fludarabine	Experimental	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)	Drug: Busulfan Drug: Melphalan Drug: Fludarabine Procedure: (CliniMACS) T-cell depleted PBSC Transplant
Clofarabine, Melphalan and Thiotepa	Experimental	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)	Drug: Thiotepa Drug: Melphalan Drug: Clofarabine Procedure: (CliniMACS) T-cell depleted PBSC Transplant
Melphalan, Fludarabine and Thiotepa	Experimental	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)

Name	Type	Description	Arm Group Labels	Other Names
total body irradiation	Radiation	dose of 1375-1500 cGy	Total Body Irradiation, Thiotepa and Cyclophosphamide

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.		3 years
Number of Participants With Acute and Chronic GVHD Following T-cell Depleted, CD34+ Progenitor Cell Enriched Transplants Fractionated by the CliniMACS System.	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).	3 years
Incidence of Non-relapse Mortality (Transplant-related Mortality) Following Each Cytoreduction Regimen and a Transplant Fractionated by the CliniMACS System.		3 years
Survival and Disease-free Survival (DFS)		at 6 months post transplant
Survival and Disease-free Survival (DFS)		1 year post transplant
Survival and Disease-free Survival (DFS)		2 years post transplant

Secondary Outcomes

Measure	Description	Time Frame
Proportion of Patients Receiving Optimal CD3+ (<1x10^5/kg) Cell Doses the Proportion of Patients Receiving CD3+ T-cell Doses > 1x10^5/kg.		Up to 3 years
Proportion of Patients Receiving Optimal CD34+ (> 5x10^6/kg) Cell Doses the Proportion Recurring Suboptimal Doses (< 2x10^6/kg) CD34+ Cells

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Malignant conditions or other life threatening disorders correctable by transplant for which CD34+ selected, T-cell depleted allogeneic hematopoietic stem cell transplantation is indicated such as:
AML in 1st remission - for patients whose AML does not have 'good risk' cytogenetic features (i.e. t 8;21, t15;17, inv 16).
Secondary AML in 1st remission
AML in 1st relapse or > than or = to 2nd remission
ALL/CLL in 1st remission clinical or molecular features indicating a high risk for relapse; or ALL/CLL > than or = to 2nd remission
CML failing to respond to or not tolerating Imatinib or dasatinib in first chronic phase of disease; CML in accelerated phase second chronic phase or in CR after accelerated phase or blast crisis.
Non-Hodgkins lymphoma with chemoresponsive disease in any of the following categories:
1. intermediate or high grade lymphomas who have failed to achieve a first CR or have relapsed following a 1st remission who are not candidates for autologous transplants.
2. any NHL in remission which is considered not curable with chemotherapy alone and not eligible/appropriate for autologous transplant.
Myelodysplastic syndrome (MDS): RA//RARS/RCMD with high risk cytogenetic features or transfusion dependence as well as RAEB-1 and RAEB-2 and Acute myelogenous leukemia (AML) evolved from MDS, who are not eligible for transplantation and/or unable to enroll onto protocol IRB 08-008.
Chronic myelomonocytic leukemia: CMML-1 and CMML-2.
Multiple Myeloma with disease in the following categories:
1. Patients with relapsed multiple myeloma following autologous stem cell transplantation who have achieved at least partial response following additional chemotherapy.
2. Patients with high risk cytogenetics at diagnosis must have achieved a partial response following autologous stem cell transplantation. Patients must have complex karyotype, del17p, t4;14 and/or t14;16 by FISH and/or del13 by karyotyping.
Other rare lethal disorders of Hematopoiesis and Lymphopoiesis for which a T-cell depleted transplant is indicated (e.g. hemophagocytic lymphohistiocytosis; refractory aplastic anemia or congenital cytopenias; non-SCID lethal genetic immunodeficiencies such as Wiskott Aldrich Syndrome, CD40 ligand deficiency, or ALPS, as well as refractory autoimmune cytopenias, PNH, metabolic storage diseases or heavily transfused congenital hemoglobinopathies).
Accrual to each treatment arm will include up to 30 standard risk and 30 poor risk patients (60 patients/treatment arm) except for Regimen D, which will include 30 patients/treatment arm, all of which will be poor risk by virtue of risks of relapse and/or transplant related mortality.
Standard risk patients will include eligible patients, as defined above, who are receiving transplants as treatment for MDS in RA//RARS/RCMD, AML in 1st or 2nd remission, ALL in 1st CR, NHL in 1st remission, MM in 1st remission, Very Good Partial Response, or 1st Partial Response or CML in the first chronic phase or 1st remission.
All other patients, including those with treatment related malignancies and/or those who have AML derived from MDS, will have received extensive prior chemo/radiotherapy and, therefore, will be considered to be at poor risk of conditioning and transplant related morbidities, and potentially transplant related mortality. Patients with life threatening non-malignant genetic and acquired disorders will also, by virtue of their history of, optional transfusions and/or infection be considered poor risk. Stopping rules for non-relapse related mortality in these heavily treated patients are, therefore, slightly less stringent than patients in the poor risk transplant groups. Stopping rules for the principal endpoints of graft failure and GvHD are the same for all groups.

The following inclusion criteria are also required:

Patient's age includes from birth on to < 70 years old.
Patients may be of either gender or any ethnic background.
Patients must have a Karnofsky (adult) or Lansky (pediatric) Performance Status > or = to 70%
Patients must have adequate organ function measured by:

Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > or = to 50% and must improve with exercise.

Hepatic: < 3x ULN AST and ≤ to 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia or if the hyperbilirubinemia is directly caused by the disease in which the patient is receiving a transplant (e.g. AML Chloroma obstructing the biliary tree). Patients with higher bilirubin levels due to causes other than active liver disease are also eligible with PI approval e.g. patients with PNH, Gilbert's disease or other hemolytic disorders.

Renal: serum creatinine < than or = to 1.2 mg/dl or if serum creatinine is outside the normal range, then CrCl > 40 ml/min (measured or calculated/estimated) Pulmonary: asymptomatic or if symptomatic, DLCO > or = to 50% of predicted (corrected for hemoglobin)

Each patient must be willing to participate as a research subject and must sign an informed consent form.

Exclusion Criteria:

Female patients who are pregnant or breast-feeding
Active viral, bacterial or fungal infection
Patient seropositive for HIV-I/II; HTLV -I/II
Presence of leukemia in the CNS.

Donor Inclusion Criteria:

Each donor must meet criteria outlined by institutional guidelines
Donor should agree to undergo general anesthesia and bone marrow harvest collection if PBSC yield is inadequate or otherwise not transplantable for whatever reason.

Donor Exclusion Criteria

If donors do not meet institutional guidelines, exclusion will be considered.

Name	Affiliation	Role
Richard O'Reilly, MD	Memorial Sloan Kettering Cancer Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Memorial Sloan Kettering Cancer Center		New York	New York	10065	United States

Label	URL
Memorial Sloan Kettering Cancer Center	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jul 21, 2021

Arm/Group Information

ID	Title	Description
BG000	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
BG001	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
BG002	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
BG003	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
BG004	Total	Total of all reporting groups

Units	Counts
Participants	BG000125 BG001213 BG00252 BG00311 BG004401

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

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

Posted

Count of Participants

Participants

3 years

ID	Title	Description
OG000	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
OG001	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
OG002	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
OG003	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

Units	Counts
Participants	OG000120 OG001210 OG00247 OG003

Title

Denominators

Categories

Engrafted

Title	Measurements
	OG000118 OG001205 OG00245 OG003

Primary

Number of Participants With Acute and Chronic GVHD Following T-cell Depleted, CD34+ Progenitor Cell Enriched Transplants Fractionated by the CliniMACS System.

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).

Posted

Number

participants

3 years

ID	Title	Description
OG000	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
OG001	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

Primary

Incidence of Non-relapse Mortality (Transplant-related Mortality) Following Each Cytoreduction Regimen and a Transplant Fractionated by the CliniMACS System.

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

Posted

Count of Participants

Participants

3 years

ID	Title	Description
OG000	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
OG001	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

Primary

Survival and Disease-free Survival (DFS)

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

Posted

Number

percentage of participants

at 6 months post transplant

ID	Title	Description
OG000	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
OG001	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
OG002	Clofarabine, Melphalan and Thiotepa

Primary

Survival and Disease-free Survival (DFS)

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

Posted

Number

% of pts at 1 year post transplant

1 year post transplant

ID	Title	Description
OG000	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
OG001	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
OG002	Clofarabine, Melphalan and Thiotepa

Primary

Survival and Disease-free Survival (DFS)

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

Posted

Number

% of pts at 2 years

2 years post transplant

ID	Title	Description
OG000	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
OG001	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
OG002	Clofarabine, Melphalan and Thiotepa

Secondary

Proportion of Patients Receiving Optimal CD3+ (<1x10^5/kg) Cell Doses the Proportion of Patients Receiving CD3+ T-cell Doses > 1x10^5/kg.

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.

Posted

Count of Participants

Participants

Up to 3 years

ID	Title	Description
OG000	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
OG001	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

Secondary

Proportion of Patients Receiving Optimal CD34+ (> 5x10^6/kg) Cell Doses the Proportion Recurring Suboptimal Doses (< 2x10^6/kg) CD34+ Cells

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

Posted

Count of Participants

Participants

3 years

ID	Title	Description
OG000	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
OG001	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
OG002

Secondary

Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment

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

Posted

Count of Participants

Participants

3 years

ID	Title	Description
OG000	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
OG001	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
OG002	Clofarabine, Melphalan and Thiotepa

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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	42	120	13	125	16	125
EG001	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	71	210	30	213	31	213
EG002	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	18	47	9	52	9	52
EG003	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	3	11	3	11	3	11

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Acidosis	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected125 at risk EG0011 affected213 at risk EG0020 affected52 at risk EG0030 affected11 at risk
Acute kidney injury	Renal and urinary disorders	Systematic Assessment	EG0000 affected125 at risk EG0011 affected213 at risk EG0021 affected52 at risk EG003
Appendicitis	Infections and infestations	Systematic Assessment	EG0000 affected125 at risk EG0011 affected213 at risk EG0020 affected52 at risk EG003
Cardiac arrest	Cardiac disorders	Systematic Assessment	EG0000 affected125 at risk EG0013 affected213 at risk EG0020 affected52 at risk EG003
Death NOS	General disorders	Systematic Assessment	EG0008 affected125 at risk EG00112 affected213 at risk EG0027 affected52 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG0000 affected125 at risk EG0010 affected213 at risk EG0021 affected52 at risk EG003
Gen disorders & admin site conditions Other, spec	General disorders	Systematic Assessment	EG0000 affected125 at risk EG0011 affected213 at risk EG0020 affected52 at risk EG003
Hepatobiliary disorders - Other, specify	Hepatobiliary disorders	Systematic Assessment	EG0000 affected125 at risk EG0011 affected213 at risk EG0020 affected52 at risk EG003
Hypotension	Vascular disorders	Systematic Assessment	EG0000 affected125 at risk EG0010 affected213 at risk EG0021 affected52 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0005 affected125 at risk EG0014 affected213 at risk EG0021 affected52 at risk EG003
Infections and infestations - Other, specify	Infections and infestations	Systematic Assessment	EG0000 affected125 at risk EG0013 affected213 at risk EG0020 affected52 at risk EG003
Meningitis	Infections and infestations	Systematic Assessment	EG0000 affected125 at risk EG0011 affected213 at risk EG0020 affected52 at risk EG003
Neutrophil count decreased	Investigations	Systematic Assessment	EG0000 affected125 at risk EG0011 affected213 at risk EG0021 affected52 at risk EG003
Pericardial tamponade	Cardiac disorders	Systematic Assessment	EG0001 affected125 at risk EG0010 affected213 at risk EG0020 affected52 at risk EG003
Platelet count decreased	Investigations	Systematic Assessment	EG0000 affected125 at risk EG0011 affected213 at risk EG0020 affected52 at risk EG003
Psychiatric disorders - Other, specify	Psychiatric disorders	Systematic Assessment	EG0000 affected125 at risk EG0011 affected213 at risk EG0020 affected52 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected125 at risk EG0014 affected213 at risk EG0021 affected52 at risk EG003
Sepsis	Infections and infestations	Systematic Assessment	EG0002 affected125 at risk EG0014 affected213 at risk EG0022 affected52 at risk EG003
Skin & subcutaneous tissue disorders Other, spec	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 affected125 at risk EG0010 affected213 at risk EG0020 affected52 at risk EG003
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0001 affected125 at risk EG0010 affected213 at risk EG0020 affected52 at risk EG003

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Acidosis	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected125 at risk EG0011 affected213 at risk EG0020 affected52 at risk EG0030 affected11 at risk
Acute kidney injury	Renal and urinary disorders	Systematic Assessment	EG0000 affected125 at risk EG0011 affected213 at risk EG0021 affected52 at risk EG003
Altered Mental Status	Psychiatric disorders	Systematic Assessment	EG0001 affected125 at risk EG0010 affected213 at risk EG0020 affected52 at risk EG003
Appendicitis	Infections and infestations	Systematic Assessment	EG0000 affected125 at risk EG0011 affected213 at risk EG0020 affected52 at risk EG003
Cardiac arrest	Cardiac disorders	Systematic Assessment	EG0000 affected125 at risk EG0013 affected213 at risk EG0020 affected52 at risk EG003
CMV Viremia	Infections and infestations	Systematic Assessment	EG0000 affected125 at risk EG0011 affected213 at risk EG0020 affected52 at risk EG003
Death NOS	General disorders	Systematic Assessment	EG0008 affected125 at risk EG00112 affected213 at risk EG0027 affected52 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected125 at risk EG0010 affected213 at risk EG0020 affected52 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG0000 affected125 at risk EG0010 affected213 at risk EG0021 affected52 at risk EG003
Gen disorders & admin site conditions Other, spec	General disorders	Systematic Assessment	EG0000 affected125 at risk EG0011 affected213 at risk EG0020 affected52 at risk EG003
Hepatobiliary disorders - Other, specify	Hepatobiliary disorders	Systematic Assessment	EG0000 affected125 at risk EG0011 affected213 at risk EG0020 affected52 at risk EG003
Hypotension	Vascular disorders	Systematic Assessment	EG0000 affected125 at risk EG0010 affected213 at risk EG0021 affected52 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0006 affected125 at risk EG0014 affected213 at risk EG0021 affected52 at risk EG003
Infections and infestations - Other, specify	Infections and infestations	Systematic Assessment	EG0000 affected125 at risk EG0013 affected213 at risk EG0020 affected52 at risk EG003
Meningitis	Infections and infestations	Systematic Assessment	EG0000 affected125 at risk EG0011 affected213 at risk EG0020 affected52 at risk EG003
Mucositis Oral	Gastrointestinal disorders	Systematic Assessment	EG0001 affected125 at risk EG0010 affected213 at risk EG0020 affected52 at risk EG003
Neutrophil count decreased	Investigations	Systematic Assessment	EG0000 affected125 at risk EG0011 affected213 at risk EG0021 affected52 at risk EG003
Pericardial tamponade	Cardiac disorders	Systematic Assessment	EG0001 affected125 at risk EG0010 affected213 at risk EG0020 affected52 at risk EG003
Platelet count decreased	Investigations	Systematic Assessment	EG0000 affected125 at risk EG0011 affected213 at risk EG0020 affected52 at risk EG003
Pleural Effusion	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected125 at risk EG0010 affected213 at risk EG0020 affected52 at risk EG003
Psychiatric disorders - Other, specify	Psychiatric disorders	Systematic Assessment	EG0000 affected125 at risk EG0011 affected213 at risk EG0020 affected52 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected125 at risk EG0014 affected213 at risk EG0021 affected52 at risk EG003
Sepsis	Infections and infestations	Systematic Assessment	EG0002 affected125 at risk EG0014 affected213 at risk EG0022 affected52 at risk EG003
Skin & subcutaneous tissue disorders Other, spec	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 affected125 at risk EG0010 affected213 at risk EG0020 affected52 at risk EG003
Vasovagal Reaction	Nervous system disorders	Systematic Assessment	EG0001 affected125 at risk EG0010 affected213 at risk EG0020 affected52 at risk EG003
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0001 affected125 at risk EG0010 affected213 at risk EG0020 affected52 at risk EG003

ID	Term
D054198	Precursor Cell Lymphoblastic Leukemia-Lymphoma
D015470	Leukemia, Myeloid, Acute
D009190	Myelodysplastic Syndromes
D009101	Multiple Myeloma
D007938	Leukemia

ID	Term
D007945	Leukemia, Lymphoid
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases
D007951	Leukemia, Myeloid
D001855	Bone Marrow Diseases
D054219	Neoplasms, Plasma Cell
D020141	Hemostatic Disorders
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D010265	Paraproteinemias
D001796	Blood Protein Disorders
D006474	Hemorrhagic Disorders

ID	Term
D011878	Radiotherapy
D013812	Therapeutics
D008919	Investigative Techniques
D063088	Phosphoramides
D009943	Organophosphorus Compounds
D009930	Organic Chemicals
D013721	Triethylenephosphoramide
D001388	Aziridines
D001389	Azirines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D002072	Butylene Glycols
D006018	Glycols
D000438	Alcohols
D008698	Mesylates
D000476	Alkanesulfonates
D017738	Alkanesulfonic Acids
D000473	Alkanes
D006839	Hydrocarbons, Acyclic
D013451	Sulfonic Acids
D013456	Sulfur Acids
D013457	Sulfur Compounds
D010649	Phenylalanine
D024322	Amino Acids, Aromatic
D000598	Amino Acids, Cyclic
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins
D000227	Adenine Nucleotides
D011685	Purine Nucleotides
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D001087	Arabinonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D009711	Nucleotides
D012265	Ribonucleotides

ID	Term
D014916	Whole-Body Irradiation
D013852	Thiotepa
D003520	Cyclophosphamide
D002066	Busulfan
D008558	Melphalan
C024352	fludarabine
D000077866	Clofarabine