Clinical trial NCT00187096: Natural Killer (NK) Cell Transplantation for AML
Official title: Pilot Study Of Haplo-Identical Natural Killer Cell Transplantation For Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Myeloid Leukemia
Keywords: Leukemia
Myeloid
Acute
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
First posted: 2005-09-16
Enrollment: 49
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Patients Experiencing Grade 3 or 4 Toxicities During Conditioning and up to 100 Days Post-transplant
timeFrame: Beginning at on therapy through 100 days post-transplant
measure: Proportion of Patients Experiencing Grade 3 or 4 Toxicities During Conditioning and up to 100 Days Post-transplant
timeFrame: Beginning at on therapy through 100 days post-transplant
Secondary outcomes:
measure: Duration of Engraftment of Natural Killer (NK) Cells
timeFrame: Measured at days 2, 7, 14, 21 and 28 after NK cell transplantation, and up to 189 days post transplant as clinically indicated
measure: Percent of Peak NK Cell Chimerism
timeFrame: Days 2, 7, 14, 21 and 28 after NK cell transplantation
measure: Percent of Detectable Donor NK Cells at Day 28
timeFrame: At 28 days
measure: Day That Maximum NK Cell Engraftment Was Reached
timeFrame: Day 0 through Day 28 post NK cell transplantation
measure: Number of KIR-mismatched NK Cells
timeFrame: Day 2 and day 14 post NK cell transplantation
measure: Number of Participants With Evidence of NK Cells Lysing a Target Cell Line (K562)
timeFrame: Days 2, 7, 14, 21, and 28 after NK cell transplantation
measure: Relapse-free Survival
timeFrame: Up to 2 years post NK cell transplantation
measure: Overall Survival
timeFrame: Up to 2 years post NK cell transplantation
Other outcomes:
Locations:
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Jeffrey E. Rubnitz, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rubnitz JE, Inaba H, Ribeiro RC, Pounds S, Rooney B, Bell T, Pui CH, Leung W. NKAML: a pilot study to determine the safety and feasibility of haploidentical natural killer cell transplantation in childhood acute myeloid leukemia. J Clin Oncol. 2010 Feb 20;28(6):955-9. doi: 10.1200/JCO.2009.24.4590. Epub 2010 Jan 19.