HLA-Nonidentical Stem Cell and Natural Killer Cell Transplantation for Children Less the Two Years of Age With Hematologic Malignancies

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Assisi Foundation
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00145626
First received: September 1, 2005
Last updated: January 20, 2016
Last verified: January 2016
Results First Received: June 8, 2015  
Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Acute Myeloid Leukemia
Acute Lymphocytic Leukemia
Myelodysplasia
Chronic Myeloid Leukemia
Histiocytosis
Interventions: Drug: Chemotherapy and antibodies
Device: Miltenyi Biotec CliniMACS
Procedure: Allogeneic stem cell transplantation

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
19 participants and 21 stem cell donors were enrolled between October 2006 and June 2011. The study was temporarily closed to accrual in June 2011 due to unavailability of study drug. The study was formally closed March 2015 because of continued unavailability of study drug. The 21 donors are excluded from this report.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
19 stem cell recipients were enrolled, and 5 were excluded. Two participants did not have natural killer cell infusions due to donor was unable to donate enough CD34+ cells or CD56+ cells for infusion, 1 participant became ineligible because they turned 2 years old prior to start of therapy, 1 withdrew and 1 expired.

Reporting Groups
  Description
Study Participants

Study participants received a non-TBI based preparative regimen consisting of Cyclophosphamide, fludarabine, thiotepa, melphalan, and muromonab-CD3 (OKT3) followed by an infusion of a T-lymphocyte depleted haploidentical hematopoietic stem cell graft. Seven days post-transplant, participants received an infusion of additional donor derived cells called natural killer (NK) cells.

Stem cells were obtained from donors using the Miltenyi Biotec CliniMACS stem cell selection device.


Participant Flow:   Overall Study
    Study Participants  
STARTED     19  
COMPLETED     14  
NOT COMPLETED     5  
Did not have NK infusions                 2  
Turned 2 years old before treatment                 1  
Death                 1  
Withdrawal by Subject                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All evaluable participants are included.

Reporting Groups
  Description
Alive

Group of participants who survived to at least one year post HSCT.

Study participants received a non-TBI based preparative regimen consisting of Cyclophosphamide, fludarabine, thiotepa, melphalan, and muromonab-CD3 (OKT3) followed by an infusion of a T-lymphocyte depleted haploidentical hematopoietic stem cell graft. Seven days posttransplant, participants received an infusion of additional donor derived cells called natural killer (NK) cells.

Stem cells were obtained from donors using the Miltenyi Biotec CliniMACS stem cell selection device.

Expired

Those participants who did not survive to at least one year post HSCT.

Study participants received a non-TBI based preparative regimen consisting of Cyclophosphamide, fludarabine, thiotepa, melphalan, and muromonab-CD3 (OKT3) followed by an infusion of a T-lymphocyte depleted haploidentical hematopoietic stem cell graft. Seven days posttransplant, participants received an infusion of additional donor derived cells called natural killer (NK) cells.

Stem cells were obtained from donors using the Miltenyi Biotec CliniMACS stem cell selection device.

Total Total of all reporting groups

Baseline Measures
    Alive     Expired     Total  
Number of Participants  
[units: participants]
  7     7     14  
Age  
[units: years]
Mean (Standard Deviation)
  1.0  (0.34)     1.0  (0.52)     1.0  (0.42)  
Age  
[units: years]
Median (Full Range)
  1.0  
  (0.6 to 1.5)  
  0.8  
  (0.5 to 1.8)  
  0.9  
  (0.5 to 1.8)  
Gender  
[units: participants]
     
Female     3     3     6  
Male     4     4     8  
Race/Ethnicity, Customized  
[units: Participants]
     
Black     2     2     4  
Other     1     1     2  
White     4     4     8  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   One-year Survival   [ Time Frame: One year after transplant ]

2.  Secondary:   Number of Transplant-Related Adverse Outcomes: Regimen-Related Mortality   [ Time Frame: 100 days post-transplantation ]

3.  Secondary:   Number of Transplant-Related Adverse Outcomes: Engraftment Failure   [ Time Frame: 100 days post-transplantation ]

4.  Secondary:   Number of Transplant-Related Adverse Outcomes: Fatal Acute Graft-Versus Host Disease (GVHD)   [ Time Frame: 100 days post-transplantation ]

5.  Secondary:   Factors Affecting One-year Survival: Median Age of Donor at HSCT   [ Time Frame: Up to one year after transplant ]

6.  Secondary:   Factors Affecting One-year Survival: Median Dose of CD34   [ Time Frame: Up to one year after transplant ]

7.  Secondary:   Factors Affecting One-year Survival: Median Dose of NK Cells   [ Time Frame: Up to one year after transplant ]

8.  Secondary:   Factors Affecting One-year Survival: Disease Status at HSCT   [ Time Frame: Up to one year after transplant ]

9.  Secondary:   Factors Affecting One-year Survival: Donor Type   [ Time Frame: Up to one year after transplant ]

10.  Secondary:   Factors Affecting One-year Survival: Match N/6 HLA Loci   [ Time Frame: Up to one year after transplant ]

11.  Secondary:   Factors Affecting One-year Survival: Minimal Residual Disease (MRD)   [ Time Frame: Up to one year after transplant ]

12.  Secondary:   Number of Transplant-related Adverse Outcomes   [ Time Frame: 5 Years ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

13.  Secondary:   Number of Incidences of Chronic GVHD.   [ Time Frame: Up to 5 years after transplant ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   Yes

14.  Secondary:   The Kinetics of Lymphohematopoietic Reconstitution.   [ Time Frame: Up to 5 years after transplant ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

15.  Secondary:   The Incidence of and Risk Factors for Organ Dysfunction.   [ Time Frame: Up to 5 Years after transplant ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

16.  Secondary:   The Incidence of and Risk Factors for Long-term Neurocognitive Deficit.   [ Time Frame: Up to 5 Years after transplant ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

17.  Secondary:   The Frequency of and Clinical Relevance of Minimal Residual Disease (MRD) Before and After Transplantation   [ Time Frame: Baseline and up to 5 years after transplant ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The study was limited due to the unavailability of the study drug OKT3 beginning in June 2011. The study was temporarily closed to accrual. Because OKT3 is still unavailable, the study was formally closed to accrual in March 2015.


  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: Brandon Triplett, MD
Organization: St. Jude Children's Research Hospital
phone: 866-278-5833
e-mail: referralinfo@stjude.org



Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00145626     History of Changes
Other Study ID Numbers: INFT2
NCI-2011-03671 ( Registry Identifier: NCI Clinical Trial Registration Program )
Study First Received: September 1, 2005
Results First Received: June 8, 2015
Last Updated: January 20, 2016
Health Authority: United States: Food and Drug Administration