Trial Outcomes & Findings for Natural Killer (NK) Cell Transplantation for AML (NCT NCT00187096)
NCT ID: NCT00187096
Last Updated: 2014-06-19
Results Overview
Document the number of patients experiencing grade 3 or 4 toxicities during conditioning and up to 100 days post-transplant. Toxicities were identified using Common Toxicity Criteria V 3.0 criteria.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
49 participants
Primary outcome timeframe
Beginning at on therapy through 100 days post-transplant
Results posted on
2014-06-19
Participant Flow
49 participants were recruited between October 2005 and October 2011.
49 participants were enrolled on the study. This report is based on results for 25 patients. 24 were donors and were excluded. All analyses are based on the intent-to-treat principle and therefore include all recipients with data available for the reported endpoint.
Participant milestones
| Measure |
Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine
Participants with AML in complete remission (stratum 1). AML in complete remission is defined as trilineage hematopoietic recovery with less than 5% blasts in the marrow. Arm 1 participants received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
|
Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD) (stratum 2). Participants enrolled prior to Amendment 2.0 received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
|
Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD) (stratum 2). Participants enrolled after protocol Amendment 2.0 received a novel conditioning regimen of clofarabine, etoposide and cyclophosphamide prior to NK cell transplantation.
|
|---|---|---|---|
|
Overall Study
STARTED
|
10
|
3
|
12
|
|
Overall Study
COMPLETED
|
10
|
3
|
11
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine
Participants with AML in complete remission (stratum 1). AML in complete remission is defined as trilineage hematopoietic recovery with less than 5% blasts in the marrow. Arm 1 participants received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
|
Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD) (stratum 2). Participants enrolled prior to Amendment 2.0 received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
|
Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD) (stratum 2). Participants enrolled after protocol Amendment 2.0 received a novel conditioning regimen of clofarabine, etoposide and cyclophosphamide prior to NK cell transplantation.
|
|---|---|---|---|
|
Overall Study
unacceptable toxicity
|
0
|
0
|
1
|
Baseline Characteristics
Natural Killer (NK) Cell Transplantation for AML
Baseline characteristics by cohort
| Measure |
Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine
n=10 Participants
AML in complete remission (stratum 1). AML in complete remission is defined as trilineage hematopoietic recovery with less than 5% blasts in the marrow. Arm 1 participants received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
|
Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine
n=3 Participants
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD) (stratum 2). Participants enrolled prior to Amendment 2.0 received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
|
Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
n=12 Participants
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD) (stratum 2). Participants enrolled after protocol Amendment 2.0 received a novel conditioning regimen of clofarabine, etoposide and cyclophosphamide prior to NK cell transplantation.
|
Total
n=25 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
7.26 years
STANDARD_DEVIATION 7.74 • n=93 Participants
|
6.05 years
STANDARD_DEVIATION 6.46 • n=4 Participants
|
10.11 years
STANDARD_DEVIATION 5.9 • n=27 Participants
|
8.48 years
STANDARD_DEVIATION 6.40 • n=483 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
9 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
8 Participants
n=27 Participants
|
16 Participants
n=483 Participants
|
PRIMARY outcome
Timeframe: Beginning at on therapy through 100 days post-transplantPopulation: Grade 3 and 4 toxicities were assessed using Common Toxicity Criteria V.3.0 The assessment period was from the date on therapy through 100 days post-transplant.
Document the number of patients experiencing grade 3 or 4 toxicities during conditioning and up to 100 days post-transplant. Toxicities were identified using Common Toxicity Criteria V 3.0 criteria.
Outcome measures
| Measure |
Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine
n=10 Participants
AML in complete remission (stratum 1). AML in complete remission is defined as trilineage hematopoietic recovery with less than 5% blasts in the marrow. Participants received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
|
Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine
n=3 Participants
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD). Participants enrolled prior to Amendment 2.0 received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
Refractory: ≥ 20% leukemic blasts in the bone marrow or no decrease in the percentage of blasts in the bone marrow (e.g., if a patient starts with 15% blasts and still has 15% blasts, he would have refractory disease).
Relapse: presence of ≥ 20% leukemic blasts in the bone marrow or the development of extramedullary disease after CR is achieved.
Increasing Minimal Residual Disease (MRD) indicates higher MRD levels.
|
Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
n=12 Participants
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD) (stratum 2). Participants enrolled after protocol Amendment 2 received a novel conditioning regimen of clofarabine, etoposide and cyclophosphamide prior to NK cell transplantation.
|
|---|---|---|---|
|
Number of Patients Experiencing Grade 3 or 4 Toxicities During Conditioning and up to 100 Days Post-transplant
|
2 participants
|
3 participants
|
11 participants
|
PRIMARY outcome
Timeframe: Beginning at on therapy through 100 days post-transplantPopulation: Grade 3 and 4 toxicities were assessed using Common Toxicity Criteria V.3.0 The assessment period was from the date on therapy through 100 days post-transplant.
Document the proportion of patients experiencing grade 3 or 4 toxicities during conditioning and up to 100 days post-transplant. Toxicities were identified using Common Toxicity Criteria V 3.0 criteria.
Outcome measures
| Measure |
Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine
n=10 Participants
AML in complete remission (stratum 1). AML in complete remission is defined as trilineage hematopoietic recovery with less than 5% blasts in the marrow. Participants received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
|
Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine
n=3 Participants
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD). Participants enrolled prior to Amendment 2.0 received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
Refractory: ≥ 20% leukemic blasts in the bone marrow or no decrease in the percentage of blasts in the bone marrow (e.g., if a patient starts with 15% blasts and still has 15% blasts, he would have refractory disease).
Relapse: presence of ≥ 20% leukemic blasts in the bone marrow or the development of extramedullary disease after CR is achieved.
Increasing Minimal Residual Disease (MRD) indicates higher MRD levels.
|
Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
n=12 Participants
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD) (stratum 2). Participants enrolled after protocol Amendment 2 received a novel conditioning regimen of clofarabine, etoposide and cyclophosphamide prior to NK cell transplantation.
|
|---|---|---|---|
|
Proportion of Patients Experiencing Grade 3 or 4 Toxicities During Conditioning and up to 100 Days Post-transplant
|
0.20 proportion of patients
|
1.00 proportion of patients
|
0.917 proportion of patients
|
SECONDARY outcome
Timeframe: Measured at days 2, 7, 14, 21 and 28 after NK cell transplantation, and up to 189 days post transplant as clinically indicatedPopulation: Arm 2 participants were not analyzed for this outcome as many of these patients proceeded to allogeneic stem cell transplantation following NK cell transplantation.
NK cell engraftment defined as NK cell chimerism in recipients.
Outcome measures
| Measure |
Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine
n=10 Participants
AML in complete remission (stratum 1). AML in complete remission is defined as trilineage hematopoietic recovery with less than 5% blasts in the marrow. Participants received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
|
Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD). Participants enrolled prior to Amendment 2.0 received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
Refractory: ≥ 20% leukemic blasts in the bone marrow or no decrease in the percentage of blasts in the bone marrow (e.g., if a patient starts with 15% blasts and still has 15% blasts, he would have refractory disease).
Relapse: presence of ≥ 20% leukemic blasts in the bone marrow or the development of extramedullary disease after CR is achieved.
Increasing Minimal Residual Disease (MRD) indicates higher MRD levels.
|
Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD) (stratum 2). Participants enrolled after protocol Amendment 2 received a novel conditioning regimen of clofarabine, etoposide and cyclophosphamide prior to NK cell transplantation.
|
|---|---|---|---|
|
Duration of Engraftment of Natural Killer (NK) Cells
|
10 Days
Interval 2.0 to 189.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 2, 7, 14, 21 and 28 after NK cell transplantationPopulation: Arm 2 participants were not analyzed for this outcome as many of these patients proceeded to allogeneic stem cell transplantation following NK cell transplantation.
The maximum percent of donor NK cell in recipients during a four-week period after NK cell infusion.
Outcome measures
| Measure |
Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine
n=10 Participants
AML in complete remission (stratum 1). AML in complete remission is defined as trilineage hematopoietic recovery with less than 5% blasts in the marrow. Participants received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
|
Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD). Participants enrolled prior to Amendment 2.0 received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
Refractory: ≥ 20% leukemic blasts in the bone marrow or no decrease in the percentage of blasts in the bone marrow (e.g., if a patient starts with 15% blasts and still has 15% blasts, he would have refractory disease).
Relapse: presence of ≥ 20% leukemic blasts in the bone marrow or the development of extramedullary disease after CR is achieved.
Increasing Minimal Residual Disease (MRD) indicates higher MRD levels.
|
Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD) (stratum 2). Participants enrolled after protocol Amendment 2 received a novel conditioning regimen of clofarabine, etoposide and cyclophosphamide prior to NK cell transplantation.
|
|---|---|---|---|
|
Percent of Peak NK Cell Chimerism
|
7 percent of NK cells
Interval 1.0 to 30.0
|
—
|
—
|
SECONDARY outcome
Timeframe: At 28 daysPopulation: Three of 10 participants continued to have detectable donor NK cells at week 4.
The percent of detectable donor NK cells in recipients at 28 days after NK cell infusion. Three of 10 participants had detectable donor cells at week 4. The results report the percent of detectable cells in the 3 participants.
Outcome measures
| Measure |
Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine
n=3 Participants
AML in complete remission (stratum 1). AML in complete remission is defined as trilineage hematopoietic recovery with less than 5% blasts in the marrow. Participants received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
|
Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD). Participants enrolled prior to Amendment 2.0 received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
Refractory: ≥ 20% leukemic blasts in the bone marrow or no decrease in the percentage of blasts in the bone marrow (e.g., if a patient starts with 15% blasts and still has 15% blasts, he would have refractory disease).
Relapse: presence of ≥ 20% leukemic blasts in the bone marrow or the development of extramedullary disease after CR is achieved.
Increasing Minimal Residual Disease (MRD) indicates higher MRD levels.
|
Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD) (stratum 2). Participants enrolled after protocol Amendment 2 received a novel conditioning regimen of clofarabine, etoposide and cyclophosphamide prior to NK cell transplantation.
|
|---|---|---|---|
|
Percent of Detectable Donor NK Cells at Day 28
|
29 percent of donor NK cells
Interval 7.0 to 30.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 0 through Day 28 post NK cell transplantationPopulation: Nine of the 10 participants in Arm 1 received KIR-mismatched NK donor cells.
The time elapsed after transplantation in days until peak KIR-mismatched donor NK cell expansion was reached in recipients
Outcome measures
| Measure |
Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine
n=9 Participants
AML in complete remission (stratum 1). AML in complete remission is defined as trilineage hematopoietic recovery with less than 5% blasts in the marrow. Participants received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
|
Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD). Participants enrolled prior to Amendment 2.0 received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
Refractory: ≥ 20% leukemic blasts in the bone marrow or no decrease in the percentage of blasts in the bone marrow (e.g., if a patient starts with 15% blasts and still has 15% blasts, he would have refractory disease).
Relapse: presence of ≥ 20% leukemic blasts in the bone marrow or the development of extramedullary disease after CR is achieved.
Increasing Minimal Residual Disease (MRD) indicates higher MRD levels.
|
Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD) (stratum 2). Participants enrolled after protocol Amendment 2 received a novel conditioning regimen of clofarabine, etoposide and cyclophosphamide prior to NK cell transplantation.
|
|---|---|---|---|
|
Day That Maximum NK Cell Engraftment Was Reached
|
14 number of days
Interval 7.0 to 28.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 2 and day 14 post NK cell transplantationPopulation: Nine of the 10 participants in Arm 1 received KIR-mismatched NK donor cells.
Number of KIR-mismatched donor NK cells in recipients' blood at day 2 and day 14 post NK cell infusion.
Outcome measures
| Measure |
Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine
n=9 Participants
AML in complete remission (stratum 1). AML in complete remission is defined as trilineage hematopoietic recovery with less than 5% blasts in the marrow. Participants received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
|
Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD). Participants enrolled prior to Amendment 2.0 received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
Refractory: ≥ 20% leukemic blasts in the bone marrow or no decrease in the percentage of blasts in the bone marrow (e.g., if a patient starts with 15% blasts and still has 15% blasts, he would have refractory disease).
Relapse: presence of ≥ 20% leukemic blasts in the bone marrow or the development of extramedullary disease after CR is achieved.
Increasing Minimal Residual Disease (MRD) indicates higher MRD levels.
|
Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD) (stratum 2). Participants enrolled after protocol Amendment 2 received a novel conditioning regimen of clofarabine, etoposide and cyclophosphamide prior to NK cell transplantation.
|
|---|---|---|---|
|
Number of KIR-mismatched NK Cells
Day 2
|
210 cells/µl
Interval 0.0 to 740.0
|
—
|
—
|
|
Number of KIR-mismatched NK Cells
Day 14
|
5,800 cells/µl
Interval 220.0 to
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 2, 7, 14, 21, and 28 after NK cell transplantationPopulation: All 10 participants received NK donor cells; 9 of the 10 participants received KIR-mismatched NK donor cells.
NK cells in recipient achieving ability to lyse target cell line (K562) within normal range established by donor NK cells.
Outcome measures
| Measure |
Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine
n=10 Participants
AML in complete remission (stratum 1). AML in complete remission is defined as trilineage hematopoietic recovery with less than 5% blasts in the marrow. Participants received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
|
Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD). Participants enrolled prior to Amendment 2.0 received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
Refractory: ≥ 20% leukemic blasts in the bone marrow or no decrease in the percentage of blasts in the bone marrow (e.g., if a patient starts with 15% blasts and still has 15% blasts, he would have refractory disease).
Relapse: presence of ≥ 20% leukemic blasts in the bone marrow or the development of extramedullary disease after CR is achieved.
Increasing Minimal Residual Disease (MRD) indicates higher MRD levels.
|
Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD) (stratum 2). Participants enrolled after protocol Amendment 2 received a novel conditioning regimen of clofarabine, etoposide and cyclophosphamide prior to NK cell transplantation.
|
|---|---|---|---|
|
Number of Participants With Evidence of NK Cells Lysing a Target Cell Line (K562)
Lysed within normal range
|
10 participants
|
—
|
—
|
|
Number of Participants With Evidence of NK Cells Lysing a Target Cell Line (K562)
Did not Lyse within normal range
|
0 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 2 years post NK cell transplantationFor Arm 1, the efficacy of NK cell transplantation will be reported as the proportion of participants who achieve complete or partial remission. Kaplan-Meier estimates of relapse-free survival and confidence interval was determined by binomial distribution because no events were observed. The binomial interval is based on the number of patients at risk.
Outcome measures
| Measure |
Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine
n=10 Participants
AML in complete remission (stratum 1). AML in complete remission is defined as trilineage hematopoietic recovery with less than 5% blasts in the marrow. Participants received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
|
Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD). Participants enrolled prior to Amendment 2.0 received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
Refractory: ≥ 20% leukemic blasts in the bone marrow or no decrease in the percentage of blasts in the bone marrow (e.g., if a patient starts with 15% blasts and still has 15% blasts, he would have refractory disease).
Relapse: presence of ≥ 20% leukemic blasts in the bone marrow or the development of extramedullary disease after CR is achieved.
Increasing Minimal Residual Disease (MRD) indicates higher MRD levels.
|
Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD) (stratum 2). Participants enrolled after protocol Amendment 2 received a novel conditioning regimen of clofarabine, etoposide and cyclophosphamide prior to NK cell transplantation.
|
|---|---|---|---|
|
Relapse-free Survival
|
100 Percent probability
95% Confidence Interval 0 • Interval 65.5 to 100.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 2 years post NK cell transplantationOverall survival is defined as the time relapse from on study date to death with those alive at last follow up date censored. The Kaplan-Meier method was used to compute survival probability estimates and confidence interval was determined by binomial distribution (for no events or all events) or by log hazard method. The binomial interval is based on the number of patients at risk. The confidence intervals for Arm 1 and Arm 2a were determined by binomial distribution. The confidence interval for Arm 2b was determined by log hazard method.
Outcome measures
| Measure |
Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine
n=10 Participants
AML in complete remission (stratum 1). AML in complete remission is defined as trilineage hematopoietic recovery with less than 5% blasts in the marrow. Participants received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
|
Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine
n=3 Participants
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD). Participants enrolled prior to Amendment 2.0 received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
Refractory: ≥ 20% leukemic blasts in the bone marrow or no decrease in the percentage of blasts in the bone marrow (e.g., if a patient starts with 15% blasts and still has 15% blasts, he would have refractory disease).
Relapse: presence of ≥ 20% leukemic blasts in the bone marrow or the development of extramedullary disease after CR is achieved.
Increasing Minimal Residual Disease (MRD) indicates higher MRD levels.
|
Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
n=12 Participants
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD) (stratum 2). Participants enrolled after protocol Amendment 2 received a novel conditioning regimen of clofarabine, etoposide and cyclophosphamide prior to NK cell transplantation.
|
|---|---|---|---|
|
Overall Survival
|
100 Percent probability
95% Confidence Interval 0 • Interval 65.5 to 100.0
|
0 Percent probability
95% Confidence Interval 0 • Interval 0.0 to 69.0
|
45.0 Percent probability
95% Confidence Interval 13.6 • Interval 15.5 to 71.0
|
Adverse Events
Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
Serious events: 2 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine
n=10 participants at risk
AML in complete remission (stratum 1). AML in complete remission is defined as trilineage hematopoietic recovery with less than 5% blasts in the marrow. Participants received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
|
Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine
n=3 participants at risk
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD). Participants enrolled prior to Amendment 2.0 received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
Refractory: ≥ 20% leukemic blasts in the bone marrow or no decrease in the percentage of blasts in the bone marrow (e.g., if a patient starts with 15% blasts and still has 15% blasts, he would have refractory disease).
Relapse: presence of ≥ 20% leukemic blasts in the bone marrow or the development of extramedullary disease after CR is achieved.
Increasing Minimal Residual Disease (MRD) indicates higher MRD levels.
|
Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
n=12 participants at risk
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD) (stratum 2). Participants enrolled after protocol Amendment 2 received a novel conditioning regimen of clofarabine, etoposide and cyclophosphamide prior to NK cell transplantation.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
|
10.0%
1/10 • Number of events 1 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/3 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/12 • Beginning at on therapy through 100 days post-transplant
|
|
Cardiac disorders
Hypotension
|
0.00%
0/10 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/3 • Beginning at on therapy through 100 days post-transplant
|
8.3%
1/12 • Number of events 1 • Beginning at on therapy through 100 days post-transplant
|
|
Hepatobiliary disorders
Hepatobiliary/Pancreas - Other
|
0.00%
0/10 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/3 • Beginning at on therapy through 100 days post-transplant
|
8.3%
1/12 • Number of events 1 • Beginning at on therapy through 100 days post-transplant
|
|
Infections and infestations
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils, blood
|
0.00%
0/10 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/3 • Beginning at on therapy through 100 days post-transplant
|
8.3%
1/12 • Number of events 2 • Beginning at on therapy through 100 days post-transplant
|
|
Infections and infestations
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils, Rectum
|
0.00%
0/10 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/3 • Beginning at on therapy through 100 days post-transplant
|
8.3%
1/12 • Number of events 1 • Beginning at on therapy through 100 days post-transplant
|
Other adverse events
| Measure |
Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine
n=10 participants at risk
AML in complete remission (stratum 1). AML in complete remission is defined as trilineage hematopoietic recovery with less than 5% blasts in the marrow. Participants received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
|
Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine
n=3 participants at risk
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD). Participants enrolled prior to Amendment 2.0 received a traditional conditioning regimen of cyclophosphamide and fludarabine prior to NK cell transplantation.
Refractory: ≥ 20% leukemic blasts in the bone marrow or no decrease in the percentage of blasts in the bone marrow (e.g., if a patient starts with 15% blasts and still has 15% blasts, he would have refractory disease).
Relapse: presence of ≥ 20% leukemic blasts in the bone marrow or the development of extramedullary disease after CR is achieved.
Increasing Minimal Residual Disease (MRD) indicates higher MRD levels.
|
Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
n=12 participants at risk
AML that is refractory or relapsed or AML with increasing minimal residual disease (MRD) (stratum 2). Participants enrolled after protocol Amendment 2 received a novel conditioning regimen of clofarabine, etoposide and cyclophosphamide prior to NK cell transplantation.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Hemoglobin
|
0.00%
0/10 • Beginning at on therapy through 100 days post-transplant
|
33.3%
1/3 • Number of events 1 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/12 • Beginning at on therapy through 100 days post-transplant
|
|
Gastrointestinal disorders
Anorexia
|
0.00%
0/10 • Beginning at on therapy through 100 days post-transplant
|
33.3%
1/3 • Number of events 1 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/12 • Beginning at on therapy through 100 days post-transplant
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/10 • Beginning at on therapy through 100 days post-transplant
|
33.3%
1/3 • Number of events 1 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/12 • Beginning at on therapy through 100 days post-transplant
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/10 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/3 • Beginning at on therapy through 100 days post-transplant
|
8.3%
1/12 • Number of events 1 • Beginning at on therapy through 100 days post-transplant
|
|
Gastrointestinal disorders
Typhlitis (cecal inflammation)
|
0.00%
0/10 • Beginning at on therapy through 100 days post-transplant
|
33.3%
1/3 • Number of events 1 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/12 • Beginning at on therapy through 100 days post-transplant
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/10 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/3 • Beginning at on therapy through 100 days post-transplant
|
8.3%
1/12 • Number of events 1 • Beginning at on therapy through 100 days post-transplant
|
|
General disorders
Hemorrhage, GI, Oral cavity
|
0.00%
0/10 • Beginning at on therapy through 100 days post-transplant
|
33.3%
1/3 • Number of events 1 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/12 • Beginning at on therapy through 100 days post-transplant
|
|
General disorders
Hemorrhage, pulmonary/upper respiratory, Nose
|
0.00%
0/10 • Beginning at on therapy through 100 days post-transplant
|
33.3%
1/3 • Number of events 1 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/12 • Beginning at on therapy through 100 days post-transplant
|
|
General disorders
Hemorrhage/Bleeding - Other (Specify, __)
|
0.00%
0/10 • Beginning at on therapy through 100 days post-transplant
|
33.3%
1/3 • Number of events 1 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/12 • Beginning at on therapy through 100 days post-transplant
|
|
Infections and infestations
Febrile neutropenia-fever of unknown origin without clinically or microbiologically documented infe
|
10.0%
1/10 • Number of events 1 • Beginning at on therapy through 100 days post-transplant
|
33.3%
1/3 • Number of events 1 • Beginning at on therapy through 100 days post-transplant
|
41.7%
5/12 • Number of events 9 • Beginning at on therapy through 100 days post-transplant
|
|
Infections and infestations
Infection - Other (Specify, __)
|
0.00%
0/10 • Beginning at on therapy through 100 days post-transplant
|
33.3%
1/3 • Number of events 1 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/12 • Beginning at on therapy through 100 days post-transplant
|
|
Infections and infestations
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils, Blood
|
0.00%
0/10 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/3 • Beginning at on therapy through 100 days post-transplant
|
33.3%
4/12 • Number of events 4 • Beginning at on therapy through 100 days post-transplant
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils, Blood
|
0.00%
0/10 • Beginning at on therapy through 100 days post-transplant
|
33.3%
1/3 • Number of events 1 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/12 • Beginning at on therapy through 100 days post-transplant
|
|
Metabolism and nutrition disorders
ALT, SGPT (serum glutamic pyruvic transaminase)
|
0.00%
0/10 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/3 • Beginning at on therapy through 100 days post-transplant
|
8.3%
1/12 • Number of events 1 • Beginning at on therapy through 100 days post-transplant
|
|
Metabolism and nutrition disorders
Bilirubin (hyperbilirubinemia)
|
0.00%
0/10 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/3 • Beginning at on therapy through 100 days post-transplant
|
8.3%
1/12 • Number of events 2 • Beginning at on therapy through 100 days post-transplant
|
|
Metabolism and nutrition disorders
Phosphate, serum-low (hypophosphatemia)
|
0.00%
0/10 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/3 • Beginning at on therapy through 100 days post-transplant
|
16.7%
2/12 • Number of events 2 • Beginning at on therapy through 100 days post-transplant
|
|
Renal and urinary disorders
Cystitis
|
0.00%
0/10 • Beginning at on therapy through 100 days post-transplant
|
33.3%
1/3 • Number of events 1 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/12 • Beginning at on therapy through 100 days post-transplant
|
|
Renal and urinary disorders
Phosphate, serum-low (hypokalemia)
|
0.00%
0/10 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/3 • Beginning at on therapy through 100 days post-transplant
|
16.7%
2/12 • Number of events 3 • Beginning at on therapy through 100 days post-transplant
|
|
Infections and infestations
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils, Lip/perioral
|
0.00%
0/10 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/3 • Beginning at on therapy through 100 days post-transplant
|
8.3%
1/12 • Number of events 1 • Beginning at on therapy through 100 days post-transplant
|
|
Infections and infestations
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils, Rectum
|
0.00%
0/10 • Beginning at on therapy through 100 days post-transplant
|
0.00%
0/3 • Beginning at on therapy through 100 days post-transplant
|
8.3%
1/12 • Number of events 1 • Beginning at on therapy through 100 days post-transplant
|
Additional Information
Jeffrey Rubnitz, MD
St. Jude Children's Research Hospital
Phone: 1-866-278-5833
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place