Natural Killer (NK) Cell Transplantation for AML

• Sponsor: St. Jude Children's Research Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00187096
• Collaborator: (none)
• Enrollment: 49
• Location: 1
• Arms: 2
• Duration (Months): 90
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety and efficacy of infusing natural killer cells from a donor as treatment for patients with acute myeloid leukemia in remission or who have experienced relapse.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: Cyclophosphamide, Fludarabine, Clofarabine, Etoposide, Interleukin-2; Procedure: Natural Killer Cell Infusion; Device: CliniMACS System	N/A

Detailed Description

Natural killer (NK) cells extracted from a [parental] donor are infused intravenously. Most patients are given a multi-agent chemotherapeutic conditioning regimen prior to the infusion. The conditioning regimen may be omitted for patients who have previously received traditional stem cell transplant.

Details of Treatment Plan:

Stratum 1 (AML in complete remission)

Cyclophosphamide 60 mg/kg IV Day -7 Fludarabine 25 mg/m2/day IV Days -6 through -2 Donor pheresis Day -1 Start IL-2 on Day -1, then 3 times per week x 2 weeks NK Cell purification and infusion on Day 0

Stratum 2 (AML that is refractory or relapsed or AML with increasing minimal residual disease)

Clofarabine 40 mg/m2 IV, days -6 through -2 Etoposide 100 mg/m2 IV, days -6 through -2 Cyclophosphamide 400 mg/m2 IV, days -6 through 02 Donor pheresis Day -1 Start IL-2 Day -1, and then 3 times per week x 2 weeks NK Cell purification and infusion on Day 0.

For patients who have received prior SCT, the conditioning regimen may be omitted if the NK cells are obtained from the original SCT donor.

Cytokine regimen (stratum 1 and 2): 1 million units/m2 of IL-2 given subcutaneously three times per week for two weeks (6 doses) starting on the evening of day -1.

NK Cell Transplantation (stratum 1 and 2): NK cells from haplo-identical family donor will be infused on day 0.

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Study Of Haplo-Identical Natural Killer Cell Transplantation For Acute Myeloid Leukemia
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Stratum 1 Stratum 1 (AML in complete remission) Cyclophosphamide 60 mg/kg IV Day -7 Fludarabine 25 mg/m2/day IV Days -6 through -2 Donor pheresis Day -1 Start IL-2 on Day -1, then 3 times per week x 2 weeks NK Cell purification and infusion on Day 0	Drug: Cyclophosphamide, Fludarabine, Clofarabine, Etoposide, Interleukin-2; See Detailed Description section for additional details of treatment interventions.; Procedure: Natural Killer Cell Infusion; See Detailed Description section for additional details of treatment interventions.; Device: CliniMACS System; See Detailed Description section for additional details of treatment interventions.
Experimental: Stratum 2 Stratum 2 (AML that is refractory or relapsed or AML with increasing minimal residual disease) Clofarabine 40 mg/m2 IV, days -6 through -2 Etoposide 100 mg/m2 IV, days -6 through -2 Cyclophosphamide 400 mg/m2 IV, days -6 through 02 Donor pheresis Day -1 Start IL-2 Day -1, and then 3 times per week x 2 weeks NK Cell purification and infusion on Day 0.	Drug: Cyclophosphamide, Fludarabine, Clofarabine, Etoposide, Interleukin-2; See Detailed Description section for additional details of treatment interventions.; Procedure: Natural Killer Cell Infusion; See Detailed Description section for additional details of treatment interventions.; Device: CliniMACS System; See Detailed Description section for additional details of treatment interventions.

Outcome Measures

Primary Outcome Measures

1. Number of Patients Experiencing Grade 3 or 4 Toxicities During Conditioning and up to 100 Days Post-transplant [Beginning at 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.

2. Proportion of Patients Experiencing Grade 3 or 4 Toxicities During Conditioning and up to 100 Days Post-transplant [Beginning at 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.

Secondary Outcome Measures

1. Duration of Engraftment of Natural Killer (NK) Cells [Measured at days 2, 7, 14, 21 and 28 after NK cell transplantation, and up to 189 days post transplant as clinically indicated]

   NK cell engraftment defined as NK cell chimerism in recipients.

2. Percent of Peak NK Cell Chimerism [Days 2, 7, 14, 21 and 28 after NK cell transplantation]

   The maximum percent of donor NK cell in recipients during a four-week period after NK cell infusion.

3. Percent of Detectable Donor NK Cells at Day 28 [At 28 days]

   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.

4. Day That Maximum NK Cell Engraftment Was Reached [Day 0 through Day 28 post NK cell transplantation]

   The time elapsed after transplantation in days until peak KIR-mismatched donor NK cell expansion was reached in recipients

5. Number of KIR-mismatched NK Cells [Day 2 and day 14 post NK cell transplantation]

   Number of KIR-mismatched donor NK cells in recipients' blood at day 2 and day 14 post NK cell infusion.

6. Number of Participants With Evidence of NK Cells Lysing a Target Cell Line (K562) [Days 2, 7, 14, 21, and 28 after NK cell transplantation]

   NK cells in recipient achieving ability to lyse target cell line (K562) within normal range established by donor NK cells.

7. Relapse-free Survival [Up to 2 years post NK cell transplantation]

   For 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.

8. Overall Survival [Up to 2 years post NK cell transplantation]

   Overall 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants with AML that is in complete remission, is relapsed or refractory, or with increasing minimal residual disease.

• Participants in complete remission must have recovered from toxicity of previous therapy and have evidence of bone marrow recovery

• Participants who had prior stem cell transplant (SCT) must have no evidence of GVHD and 60 or more days have elapsed since the SCT.

Exclusion Criteria:

• Participants who are pregnant

• Participants with inadequate renal, liver, or pulmonary functions

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105

Sponsors and Collaborators

• St. Jude Children's Research Hospital

Investigators

• Principal Investigator: Jeffrey E. Rubnitz, M.D., St. Jude Children's Research Hospital

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• St. Jude Children's Research Hospital

Publications

None provided.

• Responsible Party: St. Jude Children's Research Hospital
• ClinicalTrials.gov Identifier: NCT00187096
• Other Study ID Numbers: NKAML
• First Posted: Sep 16, 2005
• Last Update Posted: Jun 19, 2014
• Last Verified: Oct 1, 2013

• Keywords provided by St. Jude Children's Research Hospital: Leukemia; Myeloid; Acute
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Cyclophosphamide; Fludarabine; Etoposide; Interleukin-2; Clofarabine

Study Results

Participant Flow

Recruitment Details	49 participants were recruited between October 2005 and October 2011.
Pre-assignment Detail	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.

Arm/Group Title	Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine	Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine	Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
Arm/Group Description	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.	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.	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.
Period Title: Overall Study
STARTED	10	3	12
COMPLETED	10	3	11
NOT COMPLETED	0	0	1

Baseline Characteristics

Arm/Group Title	Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine	Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine	Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide	Total
Arm/Group Description	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.	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.	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 of all reporting groups
Overall Participants	10	3	12	25
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	7.26 (7.74)	6.05 (6.46)	10.11 (5.9)	8.48 (6.40)
Sex: Female, Male (Count of Participants)
Female	5 50%	0 0%	4 33.3%	9 36%
Male	5 50%	3 100%	8 66.7%	16 64%

Outcome Measures

1. Primary Outcome

Title	Number of Patients Experiencing Grade 3 or 4 Toxicities During Conditioning and up to 100 Days Post-transplant
Description	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.
Time Frame	Beginning at on therapy through 100 days post-transplant

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine	Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine	Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
Arm/Group Description	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.	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.	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.
Measure Participants	10	3	12
Number [participants]	2 20%	3 100%	11 91.7%

2. Primary Outcome

Title	Proportion of Patients Experiencing Grade 3 or 4 Toxicities During Conditioning and up to 100 Days Post-transplant
Description	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.
Time Frame	Beginning at on therapy through 100 days post-transplant

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine	Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine	Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
Arm/Group Description	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.	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.	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.
Measure Participants	10	3	12
Number [proportion of patients]	0.20	1.00	0.917

3. Secondary Outcome

Title	Duration of Engraftment of Natural Killer (NK) Cells
Description	NK cell engraftment defined as NK cell chimerism in recipients.
Time Frame	Measured at days 2, 7, 14, 21 and 28 after NK cell transplantation, and up to 189 days post transplant as clinically indicated

Outcome Measure Data

Analysis Population Description

Arm 2 participants were not analyzed for this outcome as many of these patients proceeded to allogeneic stem cell transplantation following NK cell transplantation.

Arm/Group Title	Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine	Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine	Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
Arm/Group Description	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.	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.	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.
Measure Participants	10	0	0
Median (Full Range) [Days]	10

4. Secondary Outcome

Title	Percent of Peak NK Cell Chimerism
Description	The maximum percent of donor NK cell in recipients during a four-week period after NK cell infusion.
Time Frame	Days 2, 7, 14, 21 and 28 after NK cell transplantation

Outcome Measure Data

Analysis Population Description

Arm 2 participants were not analyzed for this outcome as many of these patients proceeded to allogeneic stem cell transplantation following NK cell transplantation.

Arm/Group Title	Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine	Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine	Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
Arm/Group Description	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.	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.	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.
Measure Participants	10	0	0
Median (Full Range) [percent of NK cells]	7

5. Secondary Outcome

Title	Percent of Detectable Donor NK Cells at Day 28
Description	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.
Time Frame	At 28 days

Outcome Measure Data

Analysis Population Description

Three of 10 participants continued to have detectable donor NK cells at week 4.

Arm/Group Title	Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine	Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine	Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
Arm/Group Description	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.	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.	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.
Measure Participants	3	0	0
Median (Full Range) [percent of donor NK cells]	29

6. Secondary Outcome

Title	Day That Maximum NK Cell Engraftment Was Reached
Description	The time elapsed after transplantation in days until peak KIR-mismatched donor NK cell expansion was reached in recipients
Time Frame	Day 0 through Day 28 post NK cell transplantation

Outcome Measure Data

Analysis Population Description

Nine of the 10 participants in Arm 1 received KIR-mismatched NK donor cells.

Arm/Group Title	Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine	Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine	Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
Arm/Group Description	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.	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.	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.
Measure Participants	9	0	0
Median (Full Range) [number of days]	14

7. Secondary Outcome

Title	Number of KIR-mismatched NK Cells
Description	Number of KIR-mismatched donor NK cells in recipients' blood at day 2 and day 14 post NK cell infusion.
Time Frame	Day 2 and day 14 post NK cell transplantation

Outcome Measure Data

Analysis Population Description

Nine of the 10 participants in Arm 1 received KIR-mismatched NK donor cells.

Arm/Group Title	Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine	Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine	Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
Arm/Group Description	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.	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.	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.
Measure Participants	9	0	0
Day 2	210
Day 14	5,800

8. Secondary Outcome

Title	Number of Participants With Evidence of NK Cells Lysing a Target Cell Line (K562)
Description	NK cells in recipient achieving ability to lyse target cell line (K562) within normal range established by donor NK cells.
Time Frame	Days 2, 7, 14, 21, and 28 after NK cell transplantation

Outcome Measure Data

Analysis Population Description

All 10 participants received NK donor cells; 9 of the 10 participants received KIR-mismatched NK donor cells.

Arm/Group Title	Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine	Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine	Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
Arm/Group Description	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.	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.	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.
Measure Participants	10	0	0
Lysed within normal range	10 100%
Did not Lyse within normal range	0 0%

9. Secondary Outcome

Title	Relapse-free Survival
Description	For 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.
Time Frame	Up to 2 years post NK cell transplantation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine	Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine	Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
Arm/Group Description	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.	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.	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.
Measure Participants	10	0	0
Number (95% Confidence Interval) [Percent probability]	100 (0)

10. Secondary Outcome

Title	Overall Survival
Description	Overall 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.
Time Frame	Up to 2 years post NK cell transplantation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine	Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine	Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
Arm/Group Description	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.	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.	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.
Measure Participants	10	3	12
Number (95% Confidence Interval) [Percent probability]	100 (0)	0 (0)	45.0 (13.6)

Adverse Events

Time Frame	Beginning at on therapy through 100 days post-transplant
Arm/Group Title	Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine		Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine		Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
Arm/Group Description	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.		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.		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.
All Cause Mortality
	Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine		Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine		Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine		Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine		Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/10 (10%)		0/3 (0%)		2/12 (16.7%)
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)	1/10 (10%)	1	0/3 (0%)	0	0/12 (0%)	0
Cardiac disorders
Hypotension	0/10 (0%)	0	0/3 (0%)	0	1/12 (8.3%)	1
Hepatobiliary disorders
Hepatobiliary/Pancreas - Other	0/10 (0%)	0	0/3 (0%)	0	1/12 (8.3%)	1
Infections and infestations
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils, blood	0/10 (0%)	0	0/3 (0%)	0	1/12 (8.3%)	2
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils, Rectum	0/10 (0%)	0	0/3 (0%)	0	1/12 (8.3%)	1
Other (Not Including Serious) Adverse Events
	Arm 1: Conditioning Regimen: Cyclophosphamide/Fludarabine		Arm 2a: Conditioning Regimen: Cyclophosphamide/Fludarabine		Arm 2b: Conditioning: Clofarabine/Etoposide/Cyclophosphamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/10 (10%)		3/3 (100%)		11/12 (91.7%)
Blood and lymphatic system disorders
Hemoglobin	0/10 (0%)	0	1/3 (33.3%)	1	0/12 (0%)	0
Gastrointestinal disorders
Anorexia	0/10 (0%)	0	1/3 (33.3%)	1	0/12 (0%)	0
Colitis	0/10 (0%)	0	1/3 (33.3%)	1	0/12 (0%)	0
Nausea	0/10 (0%)	0	0/3 (0%)	0	1/12 (8.3%)	1
Typhlitis (cecal inflammation)	0/10 (0%)	0	1/3 (33.3%)	1	0/12 (0%)	0
Vomiting	0/10 (0%)	0	0/3 (0%)	0	1/12 (8.3%)	1
General disorders
Hemorrhage, GI, Oral cavity	0/10 (0%)	0	1/3 (33.3%)	1	0/12 (0%)	0
Hemorrhage, pulmonary/upper respiratory, Nose	0/10 (0%)	0	1/3 (33.3%)	1	0/12 (0%)	0
Hemorrhage/Bleeding - Other (Specify, __)	0/10 (0%)	0	1/3 (33.3%)	1	0/12 (0%)	0
Infections and infestations
Febrile neutropenia-fever of unknown origin without clinically or microbiologically documented infe	1/10 (10%)	1	1/3 (33.3%)	1	5/12 (41.7%)	9
Infection - Other (Specify, __)	0/10 (0%)	0	1/3 (33.3%)	1	0/12 (0%)	0
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils, Blood	0/10 (0%)	0	0/3 (0%)	0	4/12 (33.3%)	4
Infection with normal ANC or Grade 1 or 2 neutrophils, Blood	0/10 (0%)	0	1/3 (33.3%)	1	0/12 (0%)	0
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils, Lip/perioral	0/10 (0%)	0	0/3 (0%)	0	1/12 (8.3%)	1
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils, Rectum	0/10 (0%)	0	0/3 (0%)	0	1/12 (8.3%)	1
Metabolism and nutrition disorders
ALT, SGPT (serum glutamic pyruvic transaminase)	0/10 (0%)	0	0/3 (0%)	0	1/12 (8.3%)	1
Bilirubin (hyperbilirubinemia)	0/10 (0%)	0	0/3 (0%)	0	1/12 (8.3%)	2
Phosphate, serum-low (hypophosphatemia)	0/10 (0%)	0	0/3 (0%)	0	2/12 (16.7%)	2
Renal and urinary disorders
Cystitis	0/10 (0%)	0	1/3 (33.3%)	1	0/12 (0%)	0
Phosphate, serum-low (hypokalemia)	0/10 (0%)	0	0/3 (0%)	0	2/12 (16.7%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.