Acute Lymphoblastic Leukemia, Acute Myelogenous Leukemia, Multiple Myeloma, Myelodysplastic Syndrome
Conditions
Keywords
Leukemia, Multiple Myeloma, radiation, Thiotepa, cyclophosphamide, fludarabine, Clofarabine, CliniMACS device, GCSF, 10-050
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.
Interventions
RADIATIONtotal body irradiation
dose of 1375-1500 cGy
DRUGThiotepa
5 mg/kg/day x 2 or 10 mg/kg/day x 1
DRUGCyclophosphamide
60 mg/ kg/day x 2 (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated).
DRUGBusulfan
0.8 mg/kg every 6 hours x 10 or 12 doses (depending on disease) with dose modified according to pharmacokinetics
DRUGMelphalan
70mg/m2/day x 2
DRUGFludarabine
25mg/m2/ day x 5
DRUGClofarabine
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
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 69 Years
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: 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
Countries
United States
Participant flow
Pre-assignment details
2 patients received 2 separate transplants on each Arm A and C
Participants by arm
| Arm | Count |
|---|---|
| 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 | 125 |
| 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 | 213 |
| 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 | 52 |
| 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 | 11 |
| Total | 401 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Concern regarding adequacy of transplant cell dose | 2 | 1 | 0 | 0 |
| Overall Study | Intercurrent medication condition rendered patient ineligible | 0 | 3 | 0 | 0 |
| Overall Study | Relapse identified before transplant | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 6 | 0 | 0 |
Baseline characteristics
| Characteristic | Total Body Irradiation, Thiotepa and Cyclophosphamide | Total | Melphalan, Fludarabine and Thiotepa | Clofarabine, Melphalan and Thiotepa | Busulfan, Melphalan and Fludarabine |
|---|---|---|---|---|---|
| Age, Continuous | 30.3 years | 48 years | 10 years | 28.1 years | 57.6 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 38 Participants | 4 Participants | 6 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 64 Participants | 244 Participants | 5 Participants | 30 Participants | 145 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 43 Participants | 119 Participants | 2 Participants | 16 Participants | 58 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 29 Participants | 2 Participants | 5 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 33 Participants | 2 Participants | 1 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 21 Participants | 1 Participants | 5 Participants | 7 Participants |
| Race (NIH/OMB) White | 94 Participants | 317 Participants | 6 Participants | 41 Participants | 176 Participants |
| Region of Enrollment United States | 125 Participants | 401 Participants | 11 Participants | 52 Participants | 213 Participants |
| Sex: Female, Male Female | 63 Participants | 180 Participants | 5 Participants | 21 Participants | 91 Participants |
| Sex: Female, Male Male | 62 Participants | 221 Participants | 6 Participants | 31 Participants | 122 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 42 / 120 | 71 / 210 | 18 / 47 | 3 / 11 |
| other Total, other adverse events | 16 / 125 | 31 / 213 | 9 / 52 | 3 / 11 |
| serious Total, serious adverse events | 13 / 125 | 30 / 213 | 9 / 52 | 3 / 11 |
Outcome results
Primary
Incidence of Non-relapse Mortality (Transplant-related Mortality) Following Each Cytoreduction Regimen and a Transplant Fractionated by the CliniMACS System.
Time frame: 3 years
Population: Please note 13 participants were not evaluated in the data set as they received a second or third HCT on protocol.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Incidence of Non-relapse Mortality (Transplant-related Mortality) Following Each Cytoreduction Regimen and a Transplant Fractionated by the CliniMACS System. | Dead (non-relapse mortality) | 16 Participants |
| Total Body Irradiation, Thiotepa and Cyclophosphamide | 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) | 23 Participants |
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Incidence of Non-relapse Mortality (Transplant-related Mortality) Following Each Cytoreduction Regimen and a Transplant Fractionated by the CliniMACS System. | Alive | 81 Participants |
| Busulfan, Melphalan and Fludarabine | 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 |
| Busulfan, Melphalan and Fludarabine | 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 |
| Busulfan, Melphalan and Fludarabine | Incidence of Non-relapse Mortality (Transplant-related Mortality) Following Each Cytoreduction Regimen and a Transplant Fractionated by the CliniMACS System. | Alive | 145 Participants |
| Clofarabine, Melphalan and Thiotepa | Incidence of Non-relapse Mortality (Transplant-related Mortality) Following Each Cytoreduction Regimen and a Transplant Fractionated by the CliniMACS System. | Alive | 30 Participants |
| Clofarabine, Melphalan and Thiotepa | 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) | 3 Participants |
| Clofarabine, Melphalan and Thiotepa | Incidence of Non-relapse Mortality (Transplant-related Mortality) Following Each Cytoreduction Regimen and a Transplant Fractionated by the CliniMACS System. | Dead (non-relapse mortality) | 14 Participants |
| Melphalan, Fludarabine and Thiotepa | Incidence of Non-relapse Mortality (Transplant-related Mortality) Following Each Cytoreduction Regimen and a Transplant Fractionated by the CliniMACS System. | Alive | 8 Participants |
| Melphalan, Fludarabine and Thiotepa | Incidence of Non-relapse Mortality (Transplant-related Mortality) Following Each Cytoreduction Regimen and a Transplant Fractionated by the CliniMACS System. | Dead (non-relapse mortality) | 3 Participants |
| Melphalan, Fludarabine and Thiotepa | 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) | 0 Participants |
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).
Time frame: 3 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Total Body Irradiation, Thiotepa and Cyclophosphamide | 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 | 34 participants |
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Number of Participants With Acute and Chronic GVHD Following T-cell Depleted, CD34+ Progenitor Cell Enriched Transplants Fractionated by the CliniMACS System. | cGVHD, Extensive | 8 participants |
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Number of Participants With Acute and Chronic GVHD Following T-cell Depleted, CD34+ Progenitor Cell Enriched Transplants Fractionated by the CliniMACS System. | cGVHD, Limited | 2 participants |
| Busulfan, Melphalan and Fludarabine | 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 |
| Busulfan, Melphalan and Fludarabine | 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 |
| Busulfan, Melphalan and Fludarabine | 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 |
| Clofarabine, Melphalan and Thiotepa | Number of Participants With Acute and Chronic GVHD Following T-cell Depleted, CD34+ Progenitor Cell Enriched Transplants Fractionated by the CliniMACS System. | cGVHD, Limited | 1 participants |
| Clofarabine, Melphalan and Thiotepa | 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 | 10 participants |
| Clofarabine, Melphalan and Thiotepa | 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 |
| Melphalan, Fludarabine and Thiotepa | 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 | 2 participants |
| Melphalan, Fludarabine and Thiotepa | 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 |
| Melphalan, Fludarabine and Thiotepa | Number of Participants With Acute and Chronic GVHD Following T-cell Depleted, CD34+ Progenitor Cell Enriched Transplants Fractionated by the CliniMACS System. | cGVHD, Limited | 0 participants |
Primary
Survival and Disease-free Survival (DFS)
Time frame: 2 years post transplant
Population: 2 patients received 2 separate transplants on each Arm A and C
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Survival and Disease-free Survival (DFS) | Survival | 68.7 % of pts at 2 years |
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Survival and Disease-free Survival (DFS) | Disease Free Survival | 58.9 % of pts at 2 years |
| Busulfan, Melphalan and Fludarabine | Survival and Disease-free Survival (DFS) | Disease Free Survival | 62.1 % of pts at 2 years |
| Busulfan, Melphalan and Fludarabine | Survival and Disease-free Survival (DFS) | Survival | 72.1 % of pts at 2 years |
| Clofarabine, Melphalan and Thiotepa | Survival and Disease-free Survival (DFS) | Survival | 63.8 % of pts at 2 years |
| Clofarabine, Melphalan and Thiotepa | Survival and Disease-free Survival (DFS) | Disease Free Survival | 59.6 % of pts at 2 years |
| Melphalan, Fludarabine and Thiotepa | Survival and Disease-free Survival (DFS) | Survival | 71.6 % of pts at 2 years |
| Melphalan, Fludarabine and Thiotepa | Survival and Disease-free Survival (DFS) | Disease Free Survival | 62.3 % of pts at 2 years |
Primary
Survival and Disease-free Survival (DFS)
Time frame: at 6 months post transplant
Population: 2 patients received 2 separate transplants on each Arm A and C
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Survival and Disease-free Survival (DFS) | Survival | 93.3 percentage of participants |
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Survival and Disease-free Survival (DFS) | Disease Free Survival | 82.5 percentage of participants |
| Busulfan, Melphalan and Fludarabine | Survival and Disease-free Survival (DFS) | Disease Free Survival | 89.0 percentage of participants |
| Busulfan, Melphalan and Fludarabine | Survival and Disease-free Survival (DFS) | Survival | 92.4 percentage of participants |
| Clofarabine, Melphalan and Thiotepa | Survival and Disease-free Survival (DFS) | Survival | 87.2 percentage of participants |
| Clofarabine, Melphalan and Thiotepa | Survival and Disease-free Survival (DFS) | Disease Free Survival | 85.1 percentage of participants |
| Melphalan, Fludarabine and Thiotepa | Survival and Disease-free Survival (DFS) | Survival | 90.9 percentage of participants |
| Melphalan, Fludarabine and Thiotepa | Survival and Disease-free Survival (DFS) | Disease Free Survival | 90.9 percentage of participants |
Primary
Survival and Disease-free Survival (DFS)
Time frame: 1 year post transplant
Population: 2 patients received 2 separate transplants on each Arm A and C
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Survival and Disease-free Survival (DFS) | Survival | 80.8 % of pts at 1 year post transplant |
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Survival and Disease-free Survival (DFS) | Disease free survival | 68.3 % of pts at 1 year post transplant |
| Busulfan, Melphalan and Fludarabine | Survival and Disease-free Survival (DFS) | Disease free survival | 73.7 % of pts at 1 year post transplant |
| Busulfan, Melphalan and Fludarabine | Survival and Disease-free Survival (DFS) | Survival | 83.8 % of pts at 1 year post transplant |
| Clofarabine, Melphalan and Thiotepa | Survival and Disease-free Survival (DFS) | Survival | 85.1 % of pts at 1 year post transplant |
| Clofarabine, Melphalan and Thiotepa | Survival and Disease-free Survival (DFS) | Disease free survival | 83.0 % of pts at 1 year post transplant |
| Melphalan, Fludarabine and Thiotepa | Survival and Disease-free Survival (DFS) | Survival | 81.8 % of pts at 1 year post transplant |
| Melphalan, Fludarabine and Thiotepa | Survival and Disease-free Survival (DFS) | Disease free survival | 72.7 % of pts at 1 year post transplant |
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.
Time frame: 3 years
Population: Please note 13 participants were not evaluated in the data set as they received a second or third HCT on protocol.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Total Body Irradiation, Thiotepa and Cyclophosphamide | 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 | 118 Participants |
| Total Body Irradiation, Thiotepa and Cyclophosphamide | 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 |
| Total Body Irradiation, Thiotepa and Cyclophosphamide | 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 | 1 Participants |
| Total Body Irradiation, Thiotepa and Cyclophosphamide | 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 | 1 Participants |
| Busulfan, Melphalan and Fludarabine | 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 |
| Busulfan, Melphalan and Fludarabine | 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 |
| Busulfan, Melphalan and Fludarabine | 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 |
| Busulfan, Melphalan and Fludarabine | 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 |
| Clofarabine, Melphalan and Thiotepa | 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 | 2 Participants |
| Clofarabine, Melphalan and Thiotepa | 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 |
| Clofarabine, Melphalan and Thiotepa | 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 |
| Clofarabine, Melphalan and Thiotepa | 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 | 45 Participants |
| Melphalan, Fludarabine and Thiotepa | 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 |
| Melphalan, Fludarabine and Thiotepa | 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 |
| Melphalan, Fludarabine and Thiotepa | 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 | 10 Participants |
| Melphalan, Fludarabine and Thiotepa | 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 | 1 Participants |
Secondary
Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment
Time frame: 3 years
Population: Please note 13 participants were not evaluated in the data set as they received a second or third HCT on protocol.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Suboptimal(< 2x106/kg), Late Graft Failure | 0 Participants |
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Optimal (> 5x106/kg), Late Graft Failure | 1 Participants |
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Suboptimal(< 2x106/kg), Not Evaluable | 0 Participants |
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Other(2-5X106/kg), Engrafted | 15 Participants |
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Other(2-5X106/kg), Not Evaluable | 0 Participants |
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Optimal (> 5x106/kg), Not Evaluable | 1 Participants |
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Optimal (> 5x106/kg), Engrafted | 103 Participants |
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Suboptimal(< 2x106/kg), Engrafted | 0 Participants |
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Other(2-5X106/kg), Late Graft Failure | 0 Participants |
| Busulfan, Melphalan and Fludarabine | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Suboptimal(< 2x106/kg), Engrafted | 1 Participants |
| Busulfan, Melphalan and Fludarabine | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Optimal (> 5x106/kg), Not Evaluable | 0 Participants |
| Busulfan, Melphalan and Fludarabine | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Other(2-5X106/kg), Engrafted | 40 Participants |
| Busulfan, Melphalan and Fludarabine | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Other(2-5X106/kg), Not Evaluable | 0 Participants |
| Busulfan, Melphalan and Fludarabine | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Suboptimal(< 2x106/kg), Not Evaluable | 0 Participants |
| Busulfan, Melphalan and Fludarabine | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Optimal (> 5x106/kg), Late Graft Failure | 5 Participants |
| Busulfan, Melphalan and Fludarabine | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Other(2-5X106/kg), Late Graft Failure | 0 Participants |
| Busulfan, Melphalan and Fludarabine | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Optimal (> 5x106/kg), Engrafted | 163 Participants |
| Busulfan, Melphalan and Fludarabine | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Suboptimal(< 2x106/kg), Late Graft Failure | 0 Participants |
| Clofarabine, Melphalan and Thiotepa | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Other(2-5X106/kg), Not Evaluable | 0 Participants |
| Clofarabine, Melphalan and Thiotepa | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Optimal (> 5x106/kg), Engrafted | 38 Participants |
| Clofarabine, Melphalan and Thiotepa | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Optimal (> 5x106/kg), Late Graft Failure | 1 Participants |
| Clofarabine, Melphalan and Thiotepa | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Optimal (> 5x106/kg), Not Evaluable | 0 Participants |
| Clofarabine, Melphalan and Thiotepa | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Suboptimal(< 2x106/kg), Engrafted | 0 Participants |
| Clofarabine, Melphalan and Thiotepa | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Suboptimal(< 2x106/kg), Late Graft Failure | 0 Participants |
| Clofarabine, Melphalan and Thiotepa | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Suboptimal(< 2x106/kg), Not Evaluable | 0 Participants |
| Clofarabine, Melphalan and Thiotepa | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Other(2-5X106/kg), Engrafted | 7 Participants |
| Clofarabine, Melphalan and Thiotepa | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Other(2-5X106/kg), Late Graft Failure | 1 Participants |
| Melphalan, Fludarabine and Thiotepa | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Optimal (> 5x106/kg), Engrafted | 11 Participants |
| Melphalan, Fludarabine and Thiotepa | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Other(2-5X106/kg), Engrafted | 0 Participants |
| Melphalan, Fludarabine and Thiotepa | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Suboptimal(< 2x106/kg), Engrafted | 0 Participants |
| Melphalan, Fludarabine and Thiotepa | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Optimal (> 5x106/kg), Not Evaluable | 0 Participants |
| Melphalan, Fludarabine and Thiotepa | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Other(2-5X106/kg), Not Evaluable | 0 Participants |
| Melphalan, Fludarabine and Thiotepa | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Other(2-5X106/kg), Late Graft Failure | 0 Participants |
| Melphalan, Fludarabine and Thiotepa | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Optimal (> 5x106/kg), Late Graft Failure | 0 Participants |
| Melphalan, Fludarabine and Thiotepa | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Suboptimal(< 2x106/kg), Not Evaluable | 0 Participants |
| Melphalan, Fludarabine and Thiotepa | Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment | Suboptimal(< 2x106/kg), Late Graft Failure | 0 Participants |
Secondary
Proportion of Patients Receiving Optimal CD3+ (<1x10^5/kg) Cell Doses the Proportion of Patients Receiving CD3+ T-cell Doses > 1x10^5/kg.
Time frame: 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.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Total Body Irradiation, Thiotepa and Cyclophosphamide | 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 | 120 Participants |
| Total Body Irradiation, Thiotepa and Cyclophosphamide | 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 |
| Busulfan, Melphalan and Fludarabine | 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 |
| Busulfan, Melphalan and Fludarabine | 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 |
| Clofarabine, Melphalan and Thiotepa | 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 | 47 Participants |
| Clofarabine, Melphalan and Thiotepa | 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 |
| Melphalan, Fludarabine and Thiotepa | 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 | 11 Participants |
| Melphalan, Fludarabine and Thiotepa | 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 |
Secondary
Proportion of Patients Receiving Optimal CD34+ (> 5x10^6/kg) Cell Doses the Proportion Recurring Suboptimal Doses (< 2x10^6/kg) CD34+ Cells
Time frame: 3 years
Population: Please note 13 participants were not evaluated in the data set as they received a second or third HCT on protocol.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Proportion of Patients Receiving Optimal CD34+ (> 5x10^6/kg) Cell Doses the Proportion Recurring Suboptimal Doses (< 2x10^6/kg) CD34+ Cells | None | 15 Participants |
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Proportion of Patients Receiving Optimal CD34+ (> 5x10^6/kg) Cell Doses the Proportion Recurring Suboptimal Doses (< 2x10^6/kg) CD34+ Cells | Suboptimal | 0 Participants |
| Total Body Irradiation, Thiotepa and Cyclophosphamide | Proportion of Patients Receiving Optimal CD34+ (> 5x10^6/kg) Cell Doses the Proportion Recurring Suboptimal Doses (< 2x10^6/kg) CD34+ Cells | Optimal | 105 Participants |
| Busulfan, Melphalan and Fludarabine | Proportion of Patients Receiving Optimal CD34+ (> 5x10^6/kg) Cell Doses the Proportion Recurring Suboptimal Doses (< 2x10^6/kg) CD34+ Cells | Optimal | 169 Participants |
| Busulfan, Melphalan and Fludarabine | Proportion of Patients Receiving Optimal CD34+ (> 5x10^6/kg) Cell Doses the Proportion Recurring Suboptimal Doses (< 2x10^6/kg) CD34+ Cells | None | 40 Participants |
| Busulfan, Melphalan and Fludarabine | Proportion of Patients Receiving Optimal CD34+ (> 5x10^6/kg) Cell Doses the Proportion Recurring Suboptimal Doses (< 2x10^6/kg) CD34+ Cells | Suboptimal | 1 Participants |
| Clofarabine, Melphalan and Thiotepa | Proportion of Patients Receiving Optimal CD34+ (> 5x10^6/kg) Cell Doses the Proportion Recurring Suboptimal Doses (< 2x10^6/kg) CD34+ Cells | Suboptimal | 0 Participants |
| Clofarabine, Melphalan and Thiotepa | Proportion of Patients Receiving Optimal CD34+ (> 5x10^6/kg) Cell Doses the Proportion Recurring Suboptimal Doses (< 2x10^6/kg) CD34+ Cells | Optimal | 39 Participants |
| Clofarabine, Melphalan and Thiotepa | Proportion of Patients Receiving Optimal CD34+ (> 5x10^6/kg) Cell Doses the Proportion Recurring Suboptimal Doses (< 2x10^6/kg) CD34+ Cells | None | 8 Participants |
| Melphalan, Fludarabine and Thiotepa | Proportion of Patients Receiving Optimal CD34+ (> 5x10^6/kg) Cell Doses the Proportion Recurring Suboptimal Doses (< 2x10^6/kg) CD34+ Cells | Optimal | 11 Participants |
| Melphalan, Fludarabine and Thiotepa | Proportion of Patients Receiving Optimal CD34+ (> 5x10^6/kg) Cell Doses the Proportion Recurring Suboptimal Doses (< 2x10^6/kg) CD34+ Cells | None | 0 Participants |
| Melphalan, Fludarabine and Thiotepa | Proportion of Patients Receiving Optimal CD34+ (> 5x10^6/kg) Cell Doses the Proportion Recurring Suboptimal Doses (< 2x10^6/kg) CD34+ Cells | Suboptimal | 0 Participants |