Natural Killer (NK) Cell Transplantation for AML

Not Applicable

Completed

• Conditions: Acute Myeloid Leukemia
• Interventions: Drug: Cyclophosphamide, Fludarabine, Clofarabine, Etoposide, Interleukin-2; Procedure: Natural Killer Cell Infusion; Device: CliniMACS System

• Registration Number: NCT00187096
• Lead Sponsor: St. Jude Children's Research Hospital

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.

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 Timeline

• Study Start: 2005-09
• Study First Submitted: 2005-09-12
• Study First Submitted QC: 2005-09-12
• Study First Posted: 2005-09-16
• Primary Completion: 2012-02
• Results First Submitted: 2012-10-10
• Results First Submitted QC: 2012-10-10
• Results First Posted: 2012-11-09
• Study Completion: 2013-03
• Status Verified: 2013-10
• Last Update Submitted: 2014-06-18
• Last Update Posted: 2014-06-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 49

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.

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Exclusion Criteria

• Participants who are pregnant
• Participants with inadequate renal, liver, or pulmonary functions

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Stratum 1	Cyclophosphamide, Fludarabine, Clofarabine, Etoposide, Interleukin-2	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 1	Natural Killer Cell Infusion	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 1	CliniMACS System	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	Natural Killer Cell Infusion	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.
Stratum 2	CliniMACS System	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.
Stratum 2	Cyclophosphamide, Fludarabine, Clofarabine, Etoposide, Interleukin-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.

Primary Outcome Measures

Name	Time	Method
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.
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

Name	Time	Method
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.
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.
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.
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
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.
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.
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.
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.

Trial Locations

Locations (1)

St. Jude Children's Research Hospital; 🇺🇸 Memphis, Tennessee, United States