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
Sponsor
Memorial Sloan Kettering Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT01119066
Collaborator
(none)
422
1
4
130.9
3.2
Study Details
Study Description
Brief Summary
The purpose of this study is to find out the effects of using a system called CliniMACS to remove Tcells from blood stem cells. Removing T-cells may help stop a side effect called Graft-Versus-Host Disease (GVHD). Some studies have been done with CliniMACS, but the Food and Drug Administration (FDA) has not yet approved it.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
422 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Trial of Transplants From 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 and Other Lethal Hematologic Disorders
Actual Study Start Date
:
May 3, 2010
Actual Primary Completion Date
:
Mar 30, 2021
Actual Study Completion Date
:
Mar 30, 2021
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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) |
Radiation: total body irradiation
dose of 1375-1500 cGy
Drug: Thiotepa
5 mg/kg/day x 2 or 10 mg/kg/day x 1
Drug: Cyclophosphamide
60 mg/ kg/day x 2 (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated).
Procedure: (CliniMACS) T-cell depleted PBSC Transplant
|
| Experimental: 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) |
Drug: Busulfan
0.8 mg/kg every 6 hours x 10 or 12 doses (depending on disease) with dose modified according to pharmacokinetics
Drug: Melphalan
70mg/m2/day x 2
Drug: Fludarabine
25mg/m2/ day x 5
Procedure: (CliniMACS) T-cell depleted PBSC Transplant
|
| Experimental: 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) |
Drug: Thiotepa
5 mg/kg/day x 2 or 10 mg/kg/day x 1
Drug: Melphalan
70mg/m2/day x 2
Drug: 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)
Procedure: (CliniMACS) T-cell depleted PBSC Transplant
|
| Experimental: 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) |
Drug: Thiotepa
5 mg/kg/day x 2 or 10 mg/kg/day x 1
Drug: Melphalan
70mg/m2/day x 2
Procedure: (CliniMACS) T-cell depleted PBSC Transplant
|
Outcome Measures
Primary Outcome Measures
- 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. [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).
- 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 Outcome Measures
- 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 [3 years]
- Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment [3 years]
Eligibility Criteria
Criteria
Ages Eligible for Study:
N/A
to 69 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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:
-
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.
-
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:
-
Patients with relapsed multiple myeloma following autologous stem cell transplantation who have achieved at least partial response following additional chemotherapy.
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
Sponsors and Collaborators
- Memorial Sloan Kettering Cancer Center
Investigators
- Principal Investigator: Richard O'Reilly, MD, Memorial Sloan Kettering Cancer Center
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01119066
Other Study ID Numbers:
- 10-050
First Posted:
May 7, 2010
Last Update Posted:
Aug 5, 2022
Last Verified:
May 1, 2021
Keywords provided by Memorial Sloan Kettering Cancer Center
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 2 patients received 2 separate transplants on each Arm A and C |
| Arm/Group Title | Total Body Irradiation, Thiotepa and Cyclophosphamide | Busulfan, Melphalan and Fludarabine | Clofarabine, Melphalan and Thiotepa | Melphalan, Fludarabine and Thiotepa |
|---|---|---|---|---|
| Arm/Group Description | 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 (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 (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 (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 |
| Period Title: Overall Study | ||||
| STARTED | 132 | 227 | 52 | 11 |
| COMPLETED | 125 | 213 | 52 | 11 |
| NOT COMPLETED | 7 | 14 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Total Body Irradiation, Thiotepa and Cyclophosphamide | Busulfan, Melphalan and Fludarabine | Clofarabine, Melphalan and Thiotepa | Melphalan, Fludarabine and Thiotepa | Total |
|---|---|---|---|---|---|
| Arm/Group Description | 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 (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 (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 (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 of all reporting groups |
| Overall Participants | 125 | 213 | 52 | 11 | 401 |
| Age (years) [Median (Full Range) ] | |||||
| Median (Full Range) [years] |
30.3
|
57.6
|
28.1
|
10
|
48
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
63
50.4%
|
91
42.7%
|
21
40.4%
|
5
45.5%
|
180
44.9%
|
| Male |
62
49.6%
|
122
57.3%
|
31
59.6%
|
6
54.5%
|
221
55.1%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
18
14.4%
|
10
4.7%
|
6
11.5%
|
4
36.4%
|
38
9.5%
|
| Not Hispanic or Latino |
64
51.2%
|
145
68.1%
|
30
57.7%
|
5
45.5%
|
244
60.8%
|
| Unknown or Not Reported |
43
34.4%
|
58
27.2%
|
16
30.8%
|
2
18.2%
|
119
29.7%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
1
0.8%
|
0
0%
|
0
0%
|
0
0%
|
1
0.2%
|
| Asian |
9
7.2%
|
13
6.1%
|
5
9.6%
|
2
18.2%
|
29
7.2%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
13
10.4%
|
17
8%
|
1
1.9%
|
2
18.2%
|
33
8.2%
|
| White |
94
75.2%
|
176
82.6%
|
41
78.8%
|
6
54.5%
|
317
79.1%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
8
6.4%
|
7
3.3%
|
5
9.6%
|
1
9.1%
|
21
5.2%
|
| Region of Enrollment (Count of Participants) | |||||
| United States |
125
100%
|
213
100%
|
52
100%
|
11
100%
|
401
100%
|
Outcome Measures
| Title | 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. |
|---|---|
| Description | |
| Time Frame | 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Please note 13 participants were not evaluated in the data set as they received a second or third HCT on protocol. |
| Arm/Group Title | Total Body Irradiation, Thiotepa and Cyclophosphamide | Busulfan, Melphalan and Fludarabine | Clofarabine, Melphalan and Thiotepa | Melphalan, Fludarabine and Thiotepa |
|---|---|---|---|---|
| Arm/Group Description | 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 (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 (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 (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 |
| Measure Participants | 120 | 210 | 47 | 11 |
| Engrafted |
118
94.4%
|
205
96.2%
|
45
86.5%
|
10
90.9%
|
| Primary Graft Failure |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Late graft failure |
1
0.8%
|
5
2.3%
|
2
3.8%
|
1
9.1%
|
| Not Evaluable Engraftment |
1
0.8%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Acute and Chronic GVHD Following T-cell Depleted, CD34+ Progenitor Cell Enriched Transplants Fractionated by the CliniMACS System. |
|---|---|
| Description | 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). |
| Time Frame | 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Total Body Irradiation, Thiotepa and Cyclophosphamide | Busulfan, Melphalan and Fludarabine | Clofarabine, Melphalan and Thiotepa | Melphalan, Fludarabine and Thiotepa |
|---|---|---|---|---|
| Arm/Group Description | 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 (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 (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 (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 |
| Measure Participants | 44 | 65 | 12 | 3 |
| aGVHD II-IV |
34
27.2%
|
60
28.2%
|
10
19.2%
|
2
18.2%
|
| cGVHD, Limited |
2
1.6%
|
4
1.9%
|
1
1.9%
|
0
0%
|
| cGVHD, Extensive |
8
6.4%
|
1
0.5%
|
1
1.9%
|
1
9.1%
|
| Title | Incidence of Non-relapse Mortality (Transplant-related Mortality) Following Each Cytoreduction Regimen and a Transplant Fractionated by the CliniMACS System. |
|---|---|
| Description | |
| Time Frame | 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Please note 13 participants were not evaluated in the data set as they received a second or third HCT on protocol. |
| Arm/Group Title | Total Body Irradiation, Thiotepa and Cyclophosphamide | Busulfan, Melphalan and Fludarabine | Clofarabine, Melphalan and Thiotepa | Melphalan, Fludarabine and Thiotepa |
|---|---|---|---|---|
| Arm/Group Description | 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 (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 (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 (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 |
| Measure Participants | 120 | 210 | 47 | 11 |
| Alive |
81
64.8%
|
145
68.1%
|
30
57.7%
|
8
72.7%
|
| Dead (not non-relapse mortality) |
23
18.4%
|
24
11.3%
|
3
5.8%
|
0
0%
|
| Dead (non-relapse mortality) |
16
12.8%
|
41
19.2%
|
14
26.9%
|
3
27.3%
|
| Title | Survival and Disease-free Survival (DFS) |
|---|---|
| Description | |
| Time Frame | at 6 months post transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| 2 patients received 2 separate transplants on each Arm A and C |
| Arm/Group Title | Total Body Irradiation, Thiotepa and Cyclophosphamide | Busulfan, Melphalan and Fludarabine | Clofarabine, Melphalan and Thiotepa | Melphalan, Fludarabine and Thiotepa |
|---|---|---|---|---|
| Arm/Group Description | 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 (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 (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 (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 |
| Measure Participants | 125 | 213 | 52 | 11 |
| Survival |
93.3
74.6%
|
92.4
43.4%
|
87.2
167.7%
|
90.9
826.4%
|
| Disease Free Survival |
82.5
66%
|
89.0
41.8%
|
85.1
163.7%
|
90.9
826.4%
|
| Title | Survival and Disease-free Survival (DFS) |
|---|---|
| Description | |
| Time Frame | 1 year post transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| 2 patients received 2 separate transplants on each Arm A and C |
| Arm/Group Title | Total Body Irradiation, Thiotepa and Cyclophosphamide | Busulfan, Melphalan and Fludarabine | Clofarabine, Melphalan and Thiotepa | Melphalan, Fludarabine and Thiotepa |
|---|---|---|---|---|
| Arm/Group Description | 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 (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 (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 (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 |
| Measure Participants | 125 | 213 | 52 | 11 |
| Survival |
80.8
|
83.8
|
85.1
|
81.8
|
| Disease free survival |
68.3
|
73.7
|
83.0
|
72.7
|
| Title | Survival and Disease-free Survival (DFS) |
|---|---|
| Description | |
| Time Frame | 2 years post transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| 2 patients received 2 separate transplants on each Arm A and C |
| Arm/Group Title | Total Body Irradiation, Thiotepa and Cyclophosphamide | Busulfan, Melphalan and Fludarabine | Clofarabine, Melphalan and Thiotepa | Melphalan, Fludarabine and Thiotepa |
|---|---|---|---|---|
| Arm/Group Description | 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 (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 (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 (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 |
| Measure Participants | 125 | 213 | 52 | 11 |
| Survival |
68.7
|
72.1
|
63.8
|
71.6
|
| Disease Free Survival |
58.9
|
62.1
|
59.6
|
62.3
|
| Title | Proportion of Patients Receiving Optimal CD3+ (<1x10^5/kg) Cell Doses the Proportion of Patients Receiving CD3+ T-cell Doses > 1x10^5/kg. |
|---|---|
| Description | |
| Time Frame | Up to 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Total Body Irradiation, Thiotepa and Cyclophosphamide | Busulfan, Melphalan and Fludarabine | Clofarabine, Melphalan and Thiotepa | Melphalan, Fludarabine and Thiotepa |
|---|---|---|---|---|
| Arm/Group Description | 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 (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 (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 (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 |
| Measure Participants | 120 | 210 | 47 | 11 |
| CD3 Optimal |
120
96%
|
210
98.6%
|
47
90.4%
|
11
100%
|
| CD3 Suboptimal |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Proportion of Patients Receiving Optimal CD34+ (> 5x10^6/kg) Cell Doses the Proportion Recurring Suboptimal Doses (< 2x10^6/kg) CD34+ Cells |
|---|---|
| Description | |
| Time Frame | 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Please note 13 participants were not evaluated in the data set as they received a second or third HCT on protocol. |
| Arm/Group Title | Total Body Irradiation, Thiotepa and Cyclophosphamide | Busulfan, Melphalan and Fludarabine | Clofarabine, Melphalan and Thiotepa | Melphalan, Fludarabine and Thiotepa |
|---|---|---|---|---|
| Arm/Group Description | 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 (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 (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 (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 |
| Measure Participants | 120 | 210 | 47 | 11 |
| Optimal |
105
84%
|
169
79.3%
|
39
75%
|
11
100%
|
| Suboptimal |
0
0%
|
1
0.5%
|
0
0%
|
0
0%
|
| None |
15
12%
|
40
18.8%
|
8
15.4%
|
0
0%
|
| Title | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment |
|---|---|
| Description | |
| Time Frame | 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Please note 13 participants were not evaluated in the data set as they received a second or third HCT on protocol. |
| Arm/Group Title | Total Body Irradiation, Thiotepa and Cyclophosphamide | Busulfan, Melphalan and Fludarabine | Clofarabine, Melphalan and Thiotepa | Melphalan, Fludarabine and Thiotepa |
|---|---|---|---|---|
| Arm/Group Description | 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 (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 (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 (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 |
| Measure Participants | 120 | 209 | 47 | 11 |
| Optimal (> 5x106/kg), Engrafted |
103
82.4%
|
163
76.5%
|
38
73.1%
|
11
100%
|
| Optimal (> 5x106/kg), Late Graft Failure |
1
0.8%
|
5
2.3%
|
1
1.9%
|
0
0%
|
| Optimal (> 5x106/kg), Not Evaluable |
1
0.8%
|
0
0%
|
0
0%
|
0
0%
|
| Suboptimal(< 2x106/kg), Engrafted |
0
0%
|
1
0.5%
|
0
0%
|
0
0%
|
| Suboptimal(< 2x106/kg), Late Graft Failure |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Suboptimal(< 2x106/kg), Not Evaluable |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Other(2-5X106/kg), Engrafted |
15
12%
|
40
18.8%
|
7
13.5%
|
0
0%
|
| Other(2-5X106/kg), Late Graft Failure |
0
0%
|
0
0%
|
1
1.9%
|
0
0%
|
| Other(2-5X106/kg), Not Evaluable |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Adverse Events
| Time Frame | Up to 3 years | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Please note: participants were not censored from adverse event evaluation if they had a second or third transplant on protocol | |||||||
| Arm/Group Title | Total Body Irradiation, Thiotepa and Cyclophosphamide | Busulfan, Melphalan and Fludarabine | Clofarabine, Melphalan and Thiotepa | Melphalan, Fludarabine and Thiotepa | ||||
| Arm/Group Description | 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 (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 (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 (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 | ||||
All Cause Mortality |
||||||||
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Busulfan, Melphalan and Fludarabine | Clofarabine, Melphalan and Thiotepa | Melphalan, Fludarabine and Thiotepa | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 42/120 (35%) | 71/210 (33.8%) | 18/47 (38.3%) | 3/11 (27.3%) | ||||
Serious Adverse Events |
||||||||
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Busulfan, Melphalan and Fludarabine | Clofarabine, Melphalan and Thiotepa | Melphalan, Fludarabine and Thiotepa | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 13/125 (10.4%) | 30/213 (14.1%) | 9/52 (17.3%) | 3/11 (27.3%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Febrile neutropenia | 0/125 (0%) | 0/213 (0%) | 1/52 (1.9%) | 0/11 (0%) | ||||
| Cardiac disorders | ||||||||
| Cardiac arrest | 0/125 (0%) | 3/213 (1.4%) | 0/52 (0%) | 0/11 (0%) | ||||
| Pericardial tamponade | 1/125 (0.8%) | 0/213 (0%) | 0/52 (0%) | 0/11 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Vomiting | 1/125 (0.8%) | 0/213 (0%) | 0/52 (0%) | 0/11 (0%) | ||||
| General disorders | ||||||||
| Death NOS | 8/125 (6.4%) | 12/213 (5.6%) | 7/52 (13.5%) | 2/11 (18.2%) | ||||
| Gen disorders & admin site conditions Other, spec | 0/125 (0%) | 1/213 (0.5%) | 0/52 (0%) | 0/11 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Hepatobiliary disorders - Other, specify | 0/125 (0%) | 1/213 (0.5%) | 0/52 (0%) | 0/11 (0%) | ||||
| Infections and infestations | ||||||||
| Appendicitis | 0/125 (0%) | 1/213 (0.5%) | 0/52 (0%) | 0/11 (0%) | ||||
| Infections and infestations - Other, specify | 0/125 (0%) | 3/213 (1.4%) | 0/52 (0%) | 1/11 (9.1%) | ||||
| Meningitis | 0/125 (0%) | 1/213 (0.5%) | 0/52 (0%) | 0/11 (0%) | ||||
| Sepsis | 2/125 (1.6%) | 4/213 (1.9%) | 2/52 (3.8%) | 0/11 (0%) | ||||
| Investigations | ||||||||
| Neutrophil count decreased | 0/125 (0%) | 1/213 (0.5%) | 1/52 (1.9%) | 0/11 (0%) | ||||
| Platelet count decreased | 0/125 (0%) | 1/213 (0.5%) | 0/52 (0%) | 0/11 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Acidosis | 0/125 (0%) | 1/213 (0.5%) | 0/52 (0%) | 0/11 (0%) | ||||
| Psychiatric disorders | ||||||||
| Psychiatric disorders - Other, specify | 0/125 (0%) | 1/213 (0.5%) | 0/52 (0%) | 0/11 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 0/125 (0%) | 1/213 (0.5%) | 1/52 (1.9%) | 0/11 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Hypoxia | 5/125 (4%) | 4/213 (1.9%) | 1/52 (1.9%) | 0/11 (0%) | ||||
| Respiratory failure | 1/125 (0.8%) | 4/213 (1.9%) | 1/52 (1.9%) | 0/11 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Skin & subcutaneous tissue disorders Other, spec | 1/125 (0.8%) | 0/213 (0%) | 0/52 (0%) | 0/11 (0%) | ||||
| Vascular disorders | ||||||||
| Hypotension | 0/125 (0%) | 0/213 (0%) | 1/52 (1.9%) | 0/11 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Busulfan, Melphalan and Fludarabine | Clofarabine, Melphalan and Thiotepa | Melphalan, Fludarabine and Thiotepa | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 16/125 (12.8%) | 31/213 (14.6%) | 9/52 (17.3%) | 3/11 (27.3%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Febrile neutropenia | 0/125 (0%) | 0/213 (0%) | 1/52 (1.9%) | 0/11 (0%) | ||||
| Cardiac disorders | ||||||||
| Cardiac arrest | 0/125 (0%) | 3/213 (1.4%) | 0/52 (0%) | 0/11 (0%) | ||||
| Pericardial tamponade | 1/125 (0.8%) | 0/213 (0%) | 0/52 (0%) | 0/11 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Mucositis Oral | 1/125 (0.8%) | 0/213 (0%) | 0/52 (0%) | 0/11 (0%) | ||||
| Vomiting | 1/125 (0.8%) | 0/213 (0%) | 0/52 (0%) | 0/11 (0%) | ||||
| General disorders | ||||||||
| Death NOS | 8/125 (6.4%) | 12/213 (5.6%) | 7/52 (13.5%) | 2/11 (18.2%) | ||||
| Gen disorders & admin site conditions Other, spec | 0/125 (0%) | 1/213 (0.5%) | 0/52 (0%) | 0/11 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Hepatobiliary disorders - Other, specify | 0/125 (0%) | 1/213 (0.5%) | 0/52 (0%) | 0/11 (0%) | ||||
| Infections and infestations | ||||||||
| Appendicitis | 0/125 (0%) | 1/213 (0.5%) | 0/52 (0%) | 0/11 (0%) | ||||
| CMV Viremia | 0/125 (0%) | 1/213 (0.5%) | 0/52 (0%) | 0/11 (0%) | ||||
| Infections and infestations - Other, specify | 0/125 (0%) | 3/213 (1.4%) | 0/52 (0%) | 1/11 (9.1%) | ||||
| Meningitis | 0/125 (0%) | 1/213 (0.5%) | 0/52 (0%) | 0/11 (0%) | ||||
| Sepsis | 2/125 (1.6%) | 4/213 (1.9%) | 2/52 (3.8%) | 0/11 (0%) | ||||
| Investigations | ||||||||
| Neutrophil count decreased | 0/125 (0%) | 1/213 (0.5%) | 1/52 (1.9%) | 0/11 (0%) | ||||
| Platelet count decreased | 0/125 (0%) | 1/213 (0.5%) | 0/52 (0%) | 0/11 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Acidosis | 0/125 (0%) | 1/213 (0.5%) | 0/52 (0%) | 0/11 (0%) | ||||
| Nervous system disorders | ||||||||
| Vasovagal Reaction | 1/125 (0.8%) | 0/213 (0%) | 0/52 (0%) | 0/11 (0%) | ||||
| Psychiatric disorders | ||||||||
| Altered Mental Status | 1/125 (0.8%) | 0/213 (0%) | 0/52 (0%) | 0/11 (0%) | ||||
| Psychiatric disorders - Other, specify | 0/125 (0%) | 1/213 (0.5%) | 0/52 (0%) | 0/11 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 0/125 (0%) | 1/213 (0.5%) | 1/52 (1.9%) | 0/11 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Epistaxis | 1/125 (0.8%) | 0/213 (0%) | 0/52 (0%) | 0/11 (0%) | ||||
| Hypoxia | 6/125 (4.8%) | 4/213 (1.9%) | 1/52 (1.9%) | 0/11 (0%) | ||||
| Pleural Effusion | 1/125 (0.8%) | 0/213 (0%) | 0/52 (0%) | 0/11 (0%) | ||||
| Respiratory failure | 1/125 (0.8%) | 4/213 (1.9%) | 1/52 (1.9%) | 0/11 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Skin & subcutaneous tissue disorders Other, spec | 1/125 (0.8%) | 0/213 (0%) | 0/52 (0%) | 0/11 (0%) | ||||
| Vascular disorders | ||||||||
| Hypotension | 0/125 (0%) | 0/213 (0%) | 1/52 (1.9%) | 0/11 (0%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Richard O'Reilly, MD |
|---|---|
| Organization | Memorial Sloan Kettering Cancer Center |
| Phone | 646-888-2157 |
| oreillyr@MSKCC.ORG |
Responsible Party:
Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01119066
Other Study ID Numbers:
- 10-050
First Posted:
May 7, 2010
Last Update Posted:
Aug 5, 2022
Last Verified:
May 1, 2021