Leukemia
Conditions
Keywords
CliniMACS-CD34 Reagent System, Acute Leukemia, Myelodysplastic syndrome, Non Hodgkins Lymphoma, Hodgkins Disease, Multiple Myeloma, 12-016
Brief summary
The purpose of this study is to find out if getting a blood stem cell transplant with donor stem cells given over several days is better than getting a blood stem cell transplant with donor stem cells given over 1 day. We want to find out which procedure over will result in improved recovery of blood and immune function after transplant. When donor stem cells are given over various days in mice, the blood and immune system recovery is quicker.
Detailed description
This is a complex study that involves various interventions, Intervention #1: Donor Initial Stem Cell Collection; Intervention #2: Stem Cell Product Initial Processing Orders; Intervention #3 Patient Admission and Transplantation; Intervention #4: Stem cell infusion; Intervention #5: Post infusion follow up; Intervention #6: Off Study Patient and Donor Evaluation. Patients whose donor fails to collect the appropriate number of cells will receive all their cells as a bulk infusion. These patients will continue to receive a transplant on protocol but will be replaced until both arms have reached the target accrual.
Interventions
PROCEDUREallogeneic hematopoietic stem cell transplantation
Undergo allogeneic hematopoietic stem cell transplant
DEVICECliniMACS
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Patients who are considered candidates for an allogeneic stem cell transplantation as treatment for any of the following hematologic disorders: * Acute Leukemia * Myelodysplastic syndrome * Other myeloproliferative disorder (i.e. myelofibrosis, chronic myelomonocytic leukemia, or chronic myelogenous leukemia) * Non Hodgkins Lymphoma * Hodgkins Disease * Multiple Myeloma * Age includes from birth to \< 75 years old. * Patients must have a Karnofsky (adult) or Lansky (pediatric) Performance Status \> 70% * Patients must have adequate organ function measured by: * Cardiac: asymptomatic or if symptomatic then LVEF at rest must be \> 40% * Hepatic: \< 5x ULN ALT and \< 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia. * Renal: serum creatinine \<1.5 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 \> 40% of predicted (corrected for hemoglobin).
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 * Candidate for a protocol of higher priority. For the purpose of this study, the following protocols will be considered of higher priority: 10-051 Donor Inclusion Criteria: * HLA compatible related or unrelated donor, (i.e. a fully matched unmanipulated grafts or 1-2 HLA allele disparate donor for CD34 selected grafts). * Meets criteria outlined in the FACT-approved SOP for DONOR EVALUATION AND SELECTION FOR ALLOGENEIC TRANSPLANTATION in the Blood and Marrow Transplant Program Manual, document E-1 see http://mskweb5.mskcc.org/intranet/html/80312.cfm * Donor must have adequate peripheral venous catheter access for leukapheresis or must agree to placement of a central catheter. * Wt \>25kg Donor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Time to Engraftment of Neutrophils | Up to 100 weeks | Determine the effects of fractionated vs. bulk stem cell infusions on neutrophil recovery as defined by number of days with an absolute neutrophil count of less than 500 neutrophils per micro liter and time to an absolute neutrophil count (ANC) of 500. Determing the median time to ANC of \>/= 0.5 x 10\^9/L |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Assessed for Toxicities | 2 years | Participants will be assessed for toxicities with the NCI-Common Terminology for Adverse Events (CTCAE), version 4.0. |
| Median Time to Platelet Engraftment | Up to 365 days | The area under the hematopoietic recovery curve for the factors: ALC, CD4, CD8, and platelet count. The area under the curve will be computed based on recordings at days 30, 60, 100, 180, 365. Determine days to platelet engraftment by platelet count. |
| Hematopoietic Function on Day 180 | 180 days | Determine the difference of CD4+ lymphocyte recovery between the two arms on day 180 |
| Hematopoietic Function on Day 30 | 30 days | Determine the difference of CD4+ lymphocyte recovery between the two arms on day 30 |
| Hematopoietic Function on Day 360 | 360 days | Determine the difference of CD4+ lymphocyte recovery between the two arms on day 360 |
| Overall Survival | 24 months | Percentage of participants alive at 24 months |
Countries
United States
Participant flow
Pre-assignment details
The study goal was to explore fractionated HPC infusion in humans in a setting of commonly used conditioning regimens. The design included stratification of randomization by transplant type. Additional stratification would have increased the accrual target for statistical power, prolonging enrollment. In our publication reporting results of this trial (Tamari et al. JTCT 2021) we provide data stratified by treatment arm and transplant type for secondary endpoints for easier interpretation.
Participants by arm
| Arm | Count |
|---|---|
| Bulk Stem Cell Transplantation/SCT Patients receive reduced intensity or myeloablative conditioning regimen, GVHD prophylaxis, and undergo T cell depleted or no T cell depleted allogeneic SCT on day 0. After completion of study treatment, patients are followed up every 6-8 weeks for up to 24 months
allogeneic hematopoietic stem cell transplantation: Undergo allogeneic hematopoietic stem cell transplant
CliniMACS | 61 |
| Fractionated Stem Cell Transplantation/SCT Patients receive reduced intensity or myeloablative conditioning regimen, GVHD prophylaxis, and undergo T cell depleted or no T cell depleted allogeneic SCT on days 0, 2, 4, and 6. After completion of study treatment, patients are followed up every 6-8 weeks for up to 24 months
allogeneic hematopoietic stem cell transplantation: Undergo allogeneic hematopoietic stem cell transplant
CliniMACS | 55 |
| Total | 116 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Inadequate Collection | 23 | 19 |
Baseline characteristics
| Characteristic | Bulk Stem Cell Transplantation/SCT | Total | Fractionated Stem Cell Transplantation/SCT |
|---|---|---|---|
| Age, Continuous | 59 years | 59 years | 59 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 5 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 56 Participants | 111 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 5 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 8 Participants | 2 Participants |
| Race (NIH/OMB) White | 51 Participants | 99 Participants | 48 Participants |
| Region of Enrollment United States | 61 Participants | 116 Participants | 55 Participants |
| Sex: Female, Male Female | 30 Participants | 49 Participants | 19 Participants |
| Sex: Female, Male Male | 31 Participants | 67 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 26 / 61 | 23 / 55 |
| other Total, other adverse events | 38 / 61 | 36 / 55 |
| serious Total, serious adverse events | 21 / 61 | 12 / 55 |
Outcome results
Primary
Median Time to Engraftment of Neutrophils
Determine the effects of fractionated vs. bulk stem cell infusions on neutrophil recovery as defined by number of days with an absolute neutrophil count of less than 500 neutrophils per micro liter and time to an absolute neutrophil count (ANC) of 500. Determing the median time to ANC of \>/= 0.5 x 10\^9/L
Time frame: Up to 100 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bulk Stem Cell Transplantation/SCT | Median Time to Engraftment of Neutrophils | 11 days |
| Fractionated Stem Cell Transplantation/SCT | Median Time to Engraftment of Neutrophils | 11 days |
Secondary
Hematopoietic Function on Day 180
Determine the difference of CD4+ lymphocyte recovery between the two arms on day 180
Time frame: 180 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bulk Stem Cell Transplantation/SCT | Hematopoietic Function on Day 180 | 179 cells/mm^3 |
| Fractionated Stem Cell Transplantation/SCT | Hematopoietic Function on Day 180 | 111 cells/mm^3 |
Secondary
Hematopoietic Function on Day 30
Determine the difference of CD4+ lymphocyte recovery between the two arms on day 30
Time frame: 30 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bulk Stem Cell Transplantation/SCT | Hematopoietic Function on Day 30 | 0 cells/mm^3 |
| Fractionated Stem Cell Transplantation/SCT | Hematopoietic Function on Day 30 | 6 cells/mm^3 |
Secondary
Hematopoietic Function on Day 360
Determine the difference of CD4+ lymphocyte recovery between the two arms on day 360
Time frame: 360 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bulk Stem Cell Transplantation/SCT | Hematopoietic Function on Day 360 | 294 cells/mm^3 |
| Fractionated Stem Cell Transplantation/SCT | Hematopoietic Function on Day 360 | 280 cells/mm^3 |
Secondary
Median Time to Platelet Engraftment
The area under the hematopoietic recovery curve for the factors: ALC, CD4, CD8, and platelet count. The area under the curve will be computed based on recordings at days 30, 60, 100, 180, 365. Determine days to platelet engraftment by platelet count.
Time frame: Up to 365 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bulk Stem Cell Transplantation/SCT | Median Time to Platelet Engraftment | 18 days |
| Fractionated Stem Cell Transplantation/SCT | Median Time to Platelet Engraftment | 18 days |
Secondary
Number of Participants Assessed for Toxicities
Participants will be assessed for toxicities with the NCI-Common Terminology for Adverse Events (CTCAE), version 4.0.
Time frame: 2 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Bulk Stem Cell Transplantation/SCT | Number of Participants Assessed for Toxicities | Participants who experienced toxicities | 38 Participants |
| Bulk Stem Cell Transplantation/SCT | Number of Participants Assessed for Toxicities | Participants who did not experience toxicities | 23 Participants |
| Fractionated Stem Cell Transplantation/SCT | Number of Participants Assessed for Toxicities | Participants who experienced toxicities | 36 Participants |
| Fractionated Stem Cell Transplantation/SCT | Number of Participants Assessed for Toxicities | Participants who did not experience toxicities | 19 Participants |
Secondary
Overall Survival
Percentage of participants alive at 24 months
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bulk Stem Cell Transplantation/SCT | Overall Survival | 60 % of participants alive |
| Fractionated Stem Cell Transplantation/SCT | Overall Survival | 62 % of participants alive |