Natural Killer (NK) Cell Transplantation for AML

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00187096
First received: September 12, 2005
Last updated: June 18, 2014
Last verified: October 2013
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study Of Haplo-Identical Natural Killer Cell Transplantation For Acute Myeloid Leukemia

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • Number of Patients Experiencing Grade 3 or 4 Toxicities During Conditioning and up to 100 Days Post-transplant [ Time Frame: Beginning at on therapy through 100 days post-transplant ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Beginning at on therapy through 100 days post-transplant ] [ Designated as safety issue: Yes ]
    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:
  • Duration of Engraftment of Natural Killer (NK) Cells [ 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 ] [ Designated as safety issue: No ]
    NK cell engraftment defined as NK cell chimerism in recipients.

  • Percent of Peak NK Cell Chimerism [ Time Frame: Days 2, 7, 14, 21 and 28 after NK cell transplantation ] [ Designated as safety issue: No ]
    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 [ Time Frame: At 28 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 0 through Day 28 post NK cell transplantation ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 2 and day 14 post NK cell transplantation ] [ Designated as safety issue: No ]
    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) [ Time Frame: Days 2, 7, 14, 21, and 28 after NK cell transplantation ] [ Designated as safety issue: No ]
    NK cells in recipient achieving ability to lyse target cell line (K562) within normal range established by donor NK cells.

  • Relapse-free Survival [ Time Frame: Up to 2 years post NK cell transplantation ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 2 years post NK cell transplantation ] [ Designated as safety issue: No ]

    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.



Enrollment: 49
Study Start Date: September 2005
Study Completion Date: March 2013
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00187096

Locations
United States, Tennessee
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
  More Information

Additional Information:
Publications:
Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00187096     History of Changes
Other Study ID Numbers: NKAML
Study First Received: September 12, 2005
Results First Received: October 10, 2012
Last Updated: June 18, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by St. Jude Children's Research Hospital:
Leukemia
Myeloid
Acute

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia
Neoplasms by Histologic Type
Neoplasms
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Clofarabine
Etoposide
Interleukin-2
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Analgesics, Non-Narcotic
Analgesics

ClinicalTrials.gov processed this record on September 18, 2014