Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplasia, Chronic Myeloid Leukemia
Conditions
Brief summary
The purpose of this study is to determine if haplotype-mismatched HSCT is associated with an improvement in treatment-related mortality (TRM) rate at 6 months.
Interventions
RADIATIONTotal Body Irradiation
8 Gy on Day -9
DRUGThiotepa
5 mg/kg/d on Day -8 to -7
DRUGFludarabine
40 mg/m2/d on Day -6 to -3
BIOLOGICALRabbit ATG
2.5 mg/kg/d on Day -5 to -2
DRUGPalifermin
60 ug/kg (actual body weight) on Day -9 to -7 and Day 0 to +2
Sponsors
Sherif S. Farag
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients must have histologically documented AML, ALL, MDS, CML, Acute myeloid leukemia (AML) with one or more of the following criteria * CR 1 with poor risk features * CR 2, or higher order CR * Acute lymphoblastic leukemia (ALL) with one of the following criteria * CR 1 with poor risk features * CR 2, or higher order CR * Myelodysplasia, RAEB I * Donor has been identified * Age ≤ 65 years. * Performance Status 0-1.
Exclusion criteria
* Patients relapsing \<6 months after autologous SCT are not eligible. * Patients with active infections requiring oral or intravenous antibiotics are not eligible for enrollment until resolution of infection. * Non-pregnant and non-nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-related Mortality (TRM) Rate at 6 Months After Transplantation | thru 6 months after transplant | To determine if haplotype-mismatched HSCT is associated with a ≤40% treatment-related mortality (TRM) rate at 6 months after transplantation; a TRM ≥60% being considered unacceptable. The percent of patients with the exact 95% confidence interval who had treatment-related mortality within 6 months of their transplant is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Neutrophil Engraftment | Transplant (Day 0) up to 1 year | Time to neutrophil engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of neutrophil is defined as the time from transplant until absolute neutrophil count (ANC) \> 500 uL for 3 consecutive days. The median and 95% confidence intervals will be provided. |
| Chronic Graft vs. Host Disease (GvHD) | Up to 1 year | Number of unique patients who had chronic Graft vs. Host Disease (GvHD) diagnosed while on the study. |
| Regimen-related Toxicity | Up to 1 year | The number of unique patients who had adverse events that were possibly/probably/definitely related to treatment/regimen. |
| Acute Graft vs. Host Disease (GvHD) | Up to 1 year | Number of unique patients who had acute Graft vs. Host Disease (GvHD) diagnosed while on the study. |
| Frequency of Infection | Day 0 through 1 year post transplantation | Number of unique patients with bacterial and/or viral infections reported. |
| Time to Platelet Engraftment | Transplant (Day 0) up to 1 year | Time to platelet engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of platelets is defined as the time from day 0 to the first of seven consecutive days after transplantation during which the platelet count is at least 20 x109/l without transfusion support. Only patients who achieved engraftment of platelets will be included in the analysis. The median and 95% confidence intervals will be provided. |
Countries
United States
Participant flow
Recruitment details
This protocol had 9 enrolled patients, but one patient never received a transplant nor was randomized. There had been no efficacy or safety data entered for this patient, and they are excluded from the results.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Without Paliferim Total body Irradiation; Thiotepa; Fludarabine; Rabbit ATG;
Total Body Irradiation: 8 Gy on Day -9
Thiotepa: 5 mg/kg/d on Day -8 to -7
Fludarabine: 40 mg/m2/d on Day -6 to -3
Rabbit ATG: 2.5 mg/kg/d on Day -5 to -2 | 3 |
| Treatment With Palifermin Palifermin; Total Body Irradiation; Thiotepa; Fludarabine; Rabbit ATG
Total Body Irradiation: 8 Gy on Day -9
Thiotepa: 5 mg/kg/d on Day -8 to -7
Fludarabine: 40 mg/m2/d on Day -6 to -3
Rabbit ATG: 2.5 mg/kg/d on Day -5 to -2
Palifermin: 60 ug/kg (actual body weight) on Day -9 to -7 and Day 0 to +2 | 5 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 2 |
| Overall Study | Disease Progression | 1 | 2 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Treatment Without Paliferim | Treatment With Palifermin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 5 Participants | 8 Participants |
| Age, Continuous | 42.6 years STANDARD_DEVIATION 13.73 | 45.9 years STANDARD_DEVIATION 12.21 | 44.6 years STANDARD_DEVIATION 11.91 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 5 Participants | 8 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 5 / 5 |
| serious Total, serious adverse events | 0 / 3 | 1 / 5 |
Outcome results
Primary
Treatment-related Mortality (TRM) Rate at 6 Months After Transplantation
To determine if haplotype-mismatched HSCT is associated with a ≤40% treatment-related mortality (TRM) rate at 6 months after transplantation; a TRM ≥60% being considered unacceptable. The percent of patients with the exact 95% confidence interval who had treatment-related mortality within 6 months of their transplant is presented.
Time frame: thru 6 months after transplant
Population: Patients who received a transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Without Paliferim | Treatment-related Mortality (TRM) Rate at 6 Months After Transplantation | 33 percentage of patients |
| Treatment With Palifermin | Treatment-related Mortality (TRM) Rate at 6 Months After Transplantation | 0 percentage of patients |
Secondary
Acute Graft vs. Host Disease (GvHD)
Number of unique patients who had acute Graft vs. Host Disease (GvHD) diagnosed while on the study.
Time frame: Up to 1 year
Population: Patients who received a transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Without Paliferim | Acute Graft vs. Host Disease (GvHD) | 0 Participants |
| Treatment With Palifermin | Acute Graft vs. Host Disease (GvHD) | 0 Participants |
Secondary
Chronic Graft vs. Host Disease (GvHD)
Number of unique patients who had chronic Graft vs. Host Disease (GvHD) diagnosed while on the study.
Time frame: Up to 1 year
Population: Patients who received a transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Without Paliferim | Chronic Graft vs. Host Disease (GvHD) | 0 Participants |
| Treatment With Palifermin | Chronic Graft vs. Host Disease (GvHD) | 0 Participants |
Secondary
Frequency of Infection
Number of unique patients with bacterial and/or viral infections reported.
Time frame: Day 0 through 1 year post transplantation
Population: Patients who received a transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Without Paliferim | Frequency of Infection | 2 Participants |
| Treatment With Palifermin | Frequency of Infection | 5 Participants |
Secondary
Regimen-related Toxicity
The number of unique patients who had adverse events that were possibly/probably/definitely related to treatment/regimen.
Time frame: Up to 1 year
Population: Patients who received a transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Without Paliferim | Regimen-related Toxicity | 0 Participants |
| Treatment With Palifermin | Regimen-related Toxicity | 0 Participants |
Secondary
Time to Neutrophil Engraftment
Time to neutrophil engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of neutrophil is defined as the time from transplant until absolute neutrophil count (ANC) \> 500 uL for 3 consecutive days. The median and 95% confidence intervals will be provided.
Time frame: Transplant (Day 0) up to 1 year
Population: Patients who received a transplant
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Without Paliferim | Time to Neutrophil Engraftment | 15 days |
| Treatment With Palifermin | Time to Neutrophil Engraftment | 14 days |
Secondary
Time to Platelet Engraftment
Time to platelet engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of platelets is defined as the time from day 0 to the first of seven consecutive days after transplantation during which the platelet count is at least 20 x109/l without transfusion support. Only patients who achieved engraftment of platelets will be included in the analysis. The median and 95% confidence intervals will be provided.
Time frame: Transplant (Day 0) up to 1 year
Population: Patients who received a transplant and who achieved platelet recovery/engraftment of platelets
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Without Paliferim | Time to Platelet Engraftment | 22.5 days |
| Treatment With Palifermin | Time to Platelet Engraftment | 20 days |