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Trial record 20 of 939 for:    stem cells | Studies With Results

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00145626
Recruitment Status : Completed
First Posted : September 5, 2005
Results First Posted : December 14, 2015
Last Update Posted : June 19, 2017
Sponsor:
Collaborator:
Assisi Foundation
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (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
Enrollment 40
Recruitment Details 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 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.
Arm/Group Title Study Participants
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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.

Period Title: Overall Study
Started 19
Completed 14
Not Completed 5
Reason Not Completed
Did not have NK infusions             2
Turned 2 years old before treatment             1
Death             1
Withdrawal by Subject             1
Arm/Group Title Alive Expired Total
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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.

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 of all reporting groups
Overall Number of Baseline Participants 7 7 14
Hide Baseline Analysis Population Description
All evaluable participants are included.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 7 participants 7 participants 14 participants
1.0  (0.34) 1.0  (0.52) 1.0  (0.42)
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 7 participants 7 participants 14 participants
1.0
(0.6 to 1.5)
0.8
(0.5 to 1.8)
0.9
(0.5 to 1.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 7 participants 14 participants
Female
3
  42.9%
3
  42.9%
6
  42.9%
Male
4
  57.1%
4
  57.1%
8
  57.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 7 participants 7 participants 14 participants
Black 2 2 4
Other 1 1 2
White 4 4 8
1.Primary Outcome
Title One-year Survival
Hide Description

The one-year survival of infants with high-risk hematologic malignancies who receive a haploidentical transplant procedure using a total body irradiation (TBI)-excluding conditioning regimen followed by an HLA-nonidentical family donor hematopoietic stem cell (HSC) graft depleted of T cells ex vivo using the CliniMACS CD34+ selection system, with a subsequent infusion of donor NK cells purified ex vivo using the CliniMACS CD3+ depletion and CD56+ enrichment system.

The Kaplan-Meier estimate for one-year survival is reported.

Time Frame One year after transplant
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Study Participants
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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.

Overall Number of Participants Analyzed 14
Measure Type: Number
Unit of Measure: percentage of participants
50
2.Secondary Outcome
Title Number of Transplant-Related Adverse Outcomes: Regimen-Related Mortality
Hide Description The cumulative incidences of regimen-related mortality will be estimated using method of Kalbfleisch and Prentice.
Time Frame 100 days post-transplantation
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[Not Specified]
Arm/Group Title Study Participants
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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.

Overall Number of Participants Analyzed 14
Measure Type: Number
Unit of Measure: participants
3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Study Participants
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Cumulative Incidence
Estimated Value 0.214
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.114
Estimation Comments The cumulative incidence estimate and its standard error for occurrence of regimen-related mortality by the end of the first 100 days post-transplant was calculated.
3.Secondary Outcome
Title Number of Transplant-Related Adverse Outcomes: Engraftment Failure
Hide Description Engraftment failure is defined as <10% donor cell chimerism at any time point between 28 and 100 days after transplant with no evidence of disease relapse or requiring stem cell boost.
Time Frame 100 days post-transplantation
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Study Participants
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 14
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of engraftment failures
0.286
(0.084 to 0.581)
4.Secondary Outcome
Title Number of Transplant-Related Adverse Outcomes: Fatal Acute Graft-Versus Host Disease (GVHD)
Hide Description The cumulative incidence estimate for occurrence of fatal acute GVHD by the end of the first 100 days post-transplant was calculated using method of Kalbfleisch and Prentice.
Time Frame 100 days post-transplantation
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Study Participants
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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.

Overall Number of Participants Analyzed 14
Measure Type: Number
Unit of Measure: Number of Deaths
0
5.Secondary Outcome
Title Number of Incidences of Chronic GVHD.
Hide Description

Chronic GVHD was graded according to Seattle Criteria: limited or extensive. Limited is defined as localized skin and/or hepatic dysfunction. Extensive is defined as one or more of the following:

  • generalized skin involvement
  • liver histology showing chronic aggressive hepatitis, bridging necrosis or cirrhosis
  • eye dryness with Schirmer's test <5 mm wetting
  • oral: involvement of salivary glands or oral mucosa
  • other: another target organ involvement
Time Frame Up to 5 years after transplant
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Study Participants
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 14
Measure Type: Count of Participants
Unit of Measure: Participants
Extensive chronic GVHD
0
   0.0%
Limited chronic GVHD
1
   7.1%
No chronic GHVHD
13
  92.9%
6.Secondary Outcome
Title Factors Affecting One-year Survival: Median Age of Donor at HSCT
Hide Description Due to small sample size (n=14) and total number of events (n=7), the analysis to check the various factors that affect the one-year survival was not performed (using logistic and cox model).
Time Frame Up to one year after transplant
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Alive Expired Study Participants
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Group of participants who survived to at least one year post HSCT.
Those participants who did not survive to at least one year post HSCT.

Fourteen study participants were evaluable for the outcome measures. 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.

Overall Number of Participants Analyzed 7 7 14
Median (Full Range)
Unit of Measure: Years
21.5
(20.1 to 36.3)
27.2
(19.4 to 34.9)
25.73
(19.4 to 36.3)
7.Secondary Outcome
Title Factors Affecting One-year Survival: Median Dose of CD34
Hide Description Due to small sample size (n=14) and total number of events (n=7), the analysis to check the various factors that affect the one-year survival was not performed (using logistic and cox model).
Time Frame Up to one year after transplant
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Alive Expired Study Participants
Hide Arm/Group Description:
Group of participants who survived to at least one year post HSCT.
Those participants who did not survive to at least one year post HSCT.

Fourteen study participants were evaluable for the outcome measures. 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.

Overall Number of Participants Analyzed 7 7 14
Median (Full Range)
Unit of Measure: CD34 X 10^6/kg
35.2
(16.2 to 49.8)
38.3
(16.1 to 49.6)
37.8
(16.1 to 49.8)
8.Secondary Outcome
Title Factors Affecting One-year Survival: Median Dose of NK Cells
Hide Description Due to small sample size (n=14) and total number of events (n=7), the analysis to check the various factors that affect the one-year survival was not performed (using logistic and cox model).
Time Frame Up to one year after transplant
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Alive Expired Study Participants
Hide Arm/Group Description:
Group of participants who survived to at least one year post HSCT.
Those participants who did not survive to at least one year post HSCT.

Fourteen study participants were evaluable for the outcome measures. 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.

Overall Number of Participants Analyzed 7 7 14
Median (Full Range)
Unit of Measure: NKcells X 10^6/kg
40.2
(10.4 to 102.5)
37.6
(9.8 to 74.1)
38.9
(9.8 to 102.5)
9.Secondary Outcome
Title Factors Affecting One-year Survival: Disease Status at HSCT
Hide Description Due to small sample size (n=14) and total number of events (n=7), the analysis to check the various factors that affect the one-year survival was not performed (using logistic and cox model).
Time Frame Up to one year after transplant
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Alive Expired Study Participants
Hide Arm/Group Description:
Group of participants who survived to at least one year post HSCT.
Those participants who did not survive to at least one year post HSCT.

Fourteen study participants were evaluable for the outcome measures. 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.

Overall Number of Participants Analyzed 7 7 14
Measure Type: Number
Unit of Measure: participants
Active Disease 0 1 1
Complete Remission-1 6 2 8
Complete Remission-2 0 1 1
Progressive Disease 1 0 1
Relapse 0 3 3
10.Secondary Outcome
Title Factors Affecting One-year Survival: Donor Type
Hide Description Due to small sample size (n=14) and total number of events (n=7), the analysis to check the various factors that affect the one-year survival was not performed (using logistic and cox model).
Time Frame Up to one year after transplant
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Alive Expired Study Participants
Hide Arm/Group Description:
Group of participants who survived to at least one year post HSCT.
Those participants who did not survive to at least one year post HSCT.

Fourteen study participants were evaluable for the outcome measures. 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.

Overall Number of Participants Analyzed 7 7 14
Measure Type: Number
Unit of Measure: participants
Father 2 4 6
Mother 5 2 7
Uncle 0 1 1
11.Secondary Outcome
Title Factors Affecting One-year Survival: Match N/6 HLA Loci
Hide Description HLA typing determined the degree of match by looking at 6 different HLA loci. The results indicate the number of the 6 loci that matched for each participant. Due to small sample size (n=14) and total number of events (n=7), the analysis to check the various factors that affect the one-year survival was not performed (using logistic and cox model).
Time Frame Up to one year after transplant
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Alive Expired Study Participants
Hide Arm/Group Description:
Group of participants who survived to at least one year post HSCT.
Those participants who did not survive to at least one year post HSCT.

Fourteen study participants were evaluable for the outcome measures. 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.

Overall Number of Participants Analyzed 7 7 14
Measure Type: Number
Unit of Measure: participants
3/6 HLA Loci 6 3 9
4/6 HLA Loci 1 4 5
12.Secondary Outcome
Title Factors Affecting One-year Survival: Minimal Residual Disease (MRD)
Hide Description Detection of leukemia blasts in bone marrow by flow cytometry
Time Frame Up to one year after transplant
Hide Outcome Measure Data
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Only four of the 14 participants had MRD measured at the one-year time point.
Arm/Group Title Alive Expired Study Participants
Hide Arm/Group Description:
Group of participants who survived to at least one year post HSCT.
Those participants who did not survive to at least one year post HSCT.

MRD data were collected on four 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 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.

Overall Number of Participants Analyzed 3 1 4
Measure Type: Number
Unit of Measure: participants
Negative for MRD 2 1 3
Positive for MRD 1 0 1
13.Secondary Outcome
Title Incidence of and Risk Factors for Organ Dysfunction.
Hide Description The organ dysfunction will be summarized using summary statistics and assessed in a longitudinal manner and analyzed accordingly.
Time Frame Up to 5 Years after transplant
Hide Outcome Measure Data
Hide Analysis Population Description
There was not enough data available after 1 year post-transplant to evaluate long term outcomes on this study.
Arm/Group Title Study Participants
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
14.Secondary Outcome
Title Incidence of and Risk Factors for Long-term Neurocognitive Deficit.
Hide Description The long-term neurocognitive deficit will be summarized using summary statistics and assessed in a longitudinal manner and analyzed accordingly.
Time Frame Up to 5 Years after transplant
Hide Outcome Measure Data
Hide Analysis Population Description
There was not enough data available after 1 year post-transplant to evaluate long term outcomes on this study.
Arm/Group Title Study Participants
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
15.Secondary Outcome
Title Frequency of and Clinical Relevance of Minimal Residual Disease (MRD) Before and After Transplantation
Hide Description The presence or absence of MRD before and after the bone marrow transplant (BMT) and its frequency distribution will be obtained for each time point separately.
Time Frame Baseline before HSCT, 1 year post HSCT, and up to 5 years post HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
MRD data was collected on only four participants during at least one time point.
Arm/Group Title Study Participants: Before HSCT Study Participants: 1 Year Post HSCT Study Participants: 5 Years Post HSCT
Hide Arm/Group Description:
All study participants as previously described.
All study participants as previously described.
All study participants as previously described.
Overall Number of Participants Analyzed 4 4 4
Measure Type: Count of Participants
Unit of Measure: Participants
Patient 1 Number Analyzed 1 participants 1 participants 1 participants
Negative MRD 1 1 1
Positive MRD 0 0 0
Data Not Collected 0 0 0
Patient 2 Number Analyzed 1 participants 1 participants 1 participants
Negative MRD 0 0 1
Positive MRD 0 0 0
Data Not Collected 1 1 0
Patient 3 Number Analyzed 1 participants 1 participants 1 participants
Negative MRD 1 0 0
Positive MRD 0 0 0
Data Not Collected 0 1 1
Patient 4 Number Analyzed 1 participants 1 participants 1 participants
Negative MRD 0 0 0
Positive MRD 1 0 0
Data Not Collected 0 1 1
16.Secondary Outcome
Title Kinetics of Lymphohematopoietic Reconstitution
Hide Description The lymphohematopoietic reconstitution will be summarized using summary statistics and assessed in a longitudinal manner and analyzed accordingly.
Time Frame From 0-3 months after HSCT through 4-5 years after HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
Data was not available for analysis for all patients at all time points.
Arm/Group Title 0-3 Months After HSCT 3-6 Months After HSCT 6-9 Months After HSCT 9-12 Months After HSCT 1-2 Years After HSCT 2-3 Years After HSCT 3-4 Years After HSCT 4-5 Years After HSCT
Hide Arm/Group Description:
Study participants as previously described.
Study participants as previously described.
Study participants as previously described.
Study participants as previously described.
Study participants as previously described.
Study participants as previously described.
Study participants as previously described.
Study participants as previously described.
Overall Number of Participants Analyzed 14 14 14 14 14 14 14 14
Median (Full Range)
Unit of Measure: cells *10^3/µl
CD3 Lymphocyte Number Analyzed 10 participants 6 participants 6 participants 5 participants 4 participants 2 participants 4 participants 3 participants
0.22
(0.00 to 1.41)
0.57
(0.34 to 0.86)
1.15
(0.92 to 1.50)
2.24
(0.34 to 2.50)
1.65
(1.41 to 3.98)
2.88
(2.00 to 3.76)
2.65
(1.73 to 4.02)
1.87
(1.75 to 3.02)
CD3 Gamma Delta Number Analyzed 3 participants 1 participants 1 participants 1 participants 2 participants 2 participants 3 participants 3 participants
0.00
(0.00 to 0.04)
0.04
(0.04 to 0.04)
0.08
(0.08 to 0.08)
0.09
(0.09 to 0.09)
0.70
(0.30 to 1.11)
0.24
(0.11 to 0.36)
0.21
(0.11 to 0.48)
0.38
(0.14 to 0.43)
CD4 Lymphocyte Number Analyzed 10 participants 6 participants 6 participants 5 participants 4 participants 2 participants 4 participants 3 participants
0.13
(0.00 to 0.80)
0.42
(0.27 to 0.53)
0.92
(0.36 to 1.11)
1.37
(0.17 to 2.17)
0.96
(0.66 to 3.16)
1.56
(0.78 to 2.33)
1.33
(0.74 to 2.42)
1.94
(0.77 to 77.00)
CD8 Lymphocyte Number Analyzed 10 participants 6 participants 6 participants 5 participants 4 participants 2 participants 4 participants 3 participants
0.01
(0.00 to 0.57)
0.09
(0.01 to 0.43)
0.29
(0.05 to 0.45)
0.36
(0.08 to 0.86)
0.61
(0.45 to 0.71)
1.05
(0.83 to 1.28)
1.10
(0.55 to 1.38)
0.70
(0.58 to 1.04)
CD19 Lymphocyte Number Analyzed 10 participants 6 participants 6 participants 5 participants 4 participants 2 participants 4 participants 3 participants
0.26
(0.00 to 0.76)
0.48
(0.04 to 0.66)
0.61
(0.02 to 4.60)
0.52
(0.00 to 1.06)
0.45
(0.33 to 0.97)
0.56
(0.39 to 0.73)
0.56
(0.42 to 0.99)
0.43
(0.34 to 0.77)
CD56 Lymphocyte Number Analyzed 10 participants 6 participants 6 participants 5 participants 4 participants 2 participants 4 participants 3 participants
0.36
(0.00 to 1.91)
0.33
(0.09 to 0.82)
0.20
(0.14 to 0.38)
0.19
(0.08 to 2.75)
0.22
(0.07 to 0.98)
0.32
(0.21 to 0.43)
0.34
(0.13 to 0.89)
0.19
(0.17 to 0.72)
CD4/CD8 Ratio Number Analyzed 10 participants 6 participants 6 participants 5 participants 4 participants 2 participants 4 participants 3 participants
2.60
(0.00 to 34.00)
5.53
(0.63 to 71.50)
3.36
(0.80 to 28.28)
1.90
(1.90 to 8.10)
1.88
(0.82 to 4.40)
1.38
(0.90 to 1.85)
1.30
(1.20 to 1.80)
1.30
(1.10 to 1.90)
Absolute Lymphocyte Value Number Analyzed 10 participants 6 participants 6 participants 5 participants 4 participants 2 participants 4 participants 3 participants
0.88
(0.00 to 4.10)
1.29
(0.40 to 2.37)
1.95
(1.32 to 2.58)
2.90
(0.53 to 6.05)
2.59
(1.80 to 5.10)
3.76
(2.60 to 4.93)
3.65
(2.40 to 5.50)
2.40
(2.40 to 4.50)
Time Frame Adverse events are reported from the on-study date through April 2015 (up to one year post-transplant). All 16 patients who were enrolled and proceeded to transplant are included.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Study Participants
Hide Arm/Group Description

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.

All-Cause Mortality
Study Participants
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Study Participants
Affected / at Risk (%) # Events
Total   15/16 (93.75%)    
Blood and lymphatic system disorders   
Graft Failure * 1 [1]  1/16 (6.25%)  1
Graft Rejection * 1 [1]  3/16 (18.75%)  3
Leukocytosis * 1  1/16 (6.25%)  1
Post-Transplant Lymphoproliferative Disease * 1  1/16 (6.25%)  1
Cardiac disorders   
Cardiac Tamponade * 1  1/16 (6.25%)  1
Gastrointestinal disorders   
Colitis * 1  1/16 (6.25%)  1
Gastrointestinal Perforation * 1  1/16 (6.25%)  1
General disorders   
Fever without Neutropenia * 1 [2]  9/16 (56.25%)  21
Hepatobiliary disorders   
Hyperbilirubinemia * 1  1/16 (6.25%)  1
Veno-Occlusive Disease, Hepatic * 1  1/16 (6.25%)  1
Infections and infestations   
Febrile Neutropenia * 1  1/16 (6.25%)  1
Fever Without Neutropenia * 1  1/16 (6.25%)  1
Infection, Aspergillus, Central Nervous System * 1  1/16 (6.25%)  1
Infection, Methicillin Resistant Staphylococcus Aureus * 1  1/16 (6.25%)  1
Infection, RSV, Pneumonitis * 1  1/16 (6.25%)  1
Infection, Staphylococcus Aureus, Blood * 1  2/16 (12.50%)  2
Infection, Staphylococcus Epidermidis, Blood * 1  1/16 (6.25%)  2
Infection, Stenotrophomonas, Blood * 1  1/16 (6.25%)  1
Metabolism and nutrition disorders   
Hypernatremia * 1  1/16 (6.25%)  1
Nervous system disorders   
Seizure * 1  2/16 (12.50%)  3
Renal and urinary disorders   
Failure, Renal * 1  1/16 (6.25%)  1
Respiratory, thoracic and mediastinal disorders   
Hypoxia * 1  3/16 (18.75%)  4
Respiratory Distress * 1  1/16 (6.25%)  1
Vascular disorders   
Hemorrhage, Brain * 1  1/16 (6.25%)  1
Engraftment Syndrome * 1  2/16 (12.50%)  2
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (2.0)
[1]
Bone Marrow Transplantation Complex/Multicomponent Event
[2]
Constitutional Symptoms
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Study Participants
Affected / at Risk (%) # Events
Total   16/16 (100.00%)    
Blood and lymphatic system disorders   
Eosinophilia * 1  1/16 (6.25%)  1
Coagulopathy * 1  1/16 (6.25%)  1
Coagulopathy, Elevated Bleeding Times * 1  1/16 (6.25%)  1
Splenic Infarction * 1  1/16 (6.25%)  1
Cardiac disorders   
Prolonged QTc * 1  1/16 (6.25%)  1
Heart block (incomplete right bundle branch block) * 1  1/16 (6.25%)  1
Tachycardia * 1  2/16 (12.50%)  2
Edema of hand * 1  1/16 (6.25%)  1
Edema, Anasarca * 1  3/16 (18.75%)  3
Edema, Facial * 1  1/16 (6.25%)  1
Edema, Feet * 1  1/16 (6.25%)  1
Edema, Generalized * 1  1/16 (6.25%)  1
Edema, Lower Extremity * 1  1/16 (6.25%)  1
Hypertension * 1  3/16 (18.75%)  3
Hypotension * 1  3/16 (18.75%)  3
Murmur * 1  1/16 (6.25%)  1
Pulmonary Edema * 1  1/16 (6.25%)  1
Eye disorders   
Exposure Keratitis * 1  1/16 (6.25%)  1
Glaucoma, Right Eye * 1  1/16 (6.25%)  1
Hyphema, Right Eye * 1  1/16 (6.25%)  1
Gastrointestinal disorders   
Colitis * 1  1/16 (6.25%)  1
Diarrhea * 1  3/16 (18.75%)  4
Hemorrhage, Gastrointestinal, Oral * 1  1/16 (6.25%)  1
Loss of Appetite * 1  3/16 (18.75%)  3
Mucositis * 1  2/16 (12.50%)  2
Nausea * 1  2/16 (12.50%)  2
Stomatitis * 1  1/16 (6.25%)  1
Vomiting * 1  2/16 (12.50%)  2
General disorders   
Fever Without Neutrophenia * 1  6/16 (37.50%)  8
Weight Loss * 1  1/16 (6.25%)  1
Pain, Abdominal * 1  1/16 (6.25%)  1
Pain, Generalized, Multiple Sites * 1  1/16 (6.25%)  1
Pain, Gums * 1  1/16 (6.25%)  1
Pain, Throat * 1  1/16 (6.25%)  1
Cytokine Release Syndrome, Rituximab * 1  1/16 (6.25%)  1
Hepatobiliary disorders   
Failure, Hepatic * 1  1/16 (6.25%)  1
Hepatomegaly * 1  3/16 (18.75%)  3
Hypoalbuminemia * 1  1/16 (6.25%)  1
Splenomegaly * 1  1/16 (6.25%)  1
Veno-Occlusive Disease, Hepatic * 1  2/16 (12.50%)  2
Immune system disorders   
Allergic Drug Reaction, Defibrotide * 1  2/16 (12.50%)  2
Allergic Drug Reaction, OKT3 * 1  3/16 (18.75%)  3
Allergic Drug Reaction, Thiotepa * 1  1/16 (6.25%)  1
Allergic Reaction, Pure Red Blood Cells * 1  1/16 (6.25%)  1
Allergic Reaction, Platelet Transfusion * 1  1/16 (6.25%)  1
Rash, Generalized * 1  1/16 (6.25%)  1
Infections and infestations   
Febrile Neutropenia * 1  10/16 (62.50%)  12
Fever Without Neutropenia * 1  1/16 (6.25%)  1
Infection With Neutropenia, Klebsiella and Escherichia Coli, Blood * 1  1/16 (6.25%)  1
Infection Without Neutropenia, Enterococcus Faecalis, Blood * 1  2/16 (12.50%)  2
Infection With Neutropenia, Gamma Hemolytic Streptococcus, Skin * 1  1/16 (6.25%)  1
Infection, Adenovirus, Stool * 1  1/16 (6.25%)  1
Infection, Aspergillus Terreus, Lungs * 1  1/16 (6.25%)  1
Infection, Aspergillus, Retina * 1  1/16 (6.25%)  1
Infection, Candida, Diaper Area with Rash * 1  1/16 (6.25%)  1
Infection, Candidiasis, Mouth * 1  1/16 (6.25%)  1
Infection, Coagulase Negative Staph, Blood * 1  2/16 (12.50%)  2
Infection, Coagulase Negative Staphylococcus, Wrist * 1  1/16 (6.25%)  1
Infection, Influenza Virus A * 1  1/16 (6.25%)  1
Infection, Klebsiella Pneumoniae, Hickman Line * 1  1/16 (6.25%)  1
Infection, Legionella, Mucous * 1  1/16 (6.25%)  1
Infection, Pantoea Species, Blood * 1  1/16 (6.25%)  1
Infection, Parainfluenza Virus 3 * 1  1/16 (6.25%)  1
Infection, Pseudomonas Aeruginosa, Blood * 1  1/16 (6.25%)  1
Infection, Staphylococcus Aureus, Skin * 1  1/16 (6.25%)  1
Infection, Stomatococcus Mucilaginosus, Blood * 1  1/16 (6.25%)  1
Infection, Stool, Vancomycin Resistant Enterococci * 1  1/16 (6.25%)  1
Infection, Streptococcus Mitis, Hickman Line * 1  1/16 (6.25%)  1
Metabolism and nutrition disorders   
Hypernatremia * 1  1/16 (6.25%)  1
Hyperuricemia * 1  1/16 (6.25%)  1
Hypophosphatemia * 1  1/16 (6.25%)  1
Nervous system disorders   
Meningoencephalitis * 1  1/16 (6.25%)  1
Mood Alteration - Anxiety/Agitation * 1  1/16 (6.25%)  1
Renal and urinary disorders   
Renal Disease * 1  1/16 (6.25%)  1
Renal Failure * 1  1/16 (6.25%)  1
Respiratory, thoracic and mediastinal disorders   
Atelectasis * 1  1/16 (6.25%)  1
Cough * 1  2/16 (12.50%)  2
Hemorrhage, Pulmonary * 1  1/16 (6.25%)  1
Interstitial Lung Disease * 1  1/16 (6.25%)  1
Nodule, Pulmonary * 1  1/16 (6.25%)  1
Pulmonary Airspace Disease, Diffuse, Bilateral * 1  1/16 (6.25%)  1
Respiratory Distress * 1  1/16 (6.25%)  1
Respiratory Failure * 1  1/16 (6.25%)  1
Tachypnea * 1  1/16 (6.25%)  1
Skin and subcutaneous tissue disorders   
Abscess, Longissimus Colli, left * 1  1/16 (6.25%)  1
Erythema, Face * 1  1/16 (6.25%)  1
Erythema, Genitourinary * 1  1/16 (6.25%)  1
Erythema, Labia, Perianal Region * 1  1/16 (6.25%)  1
Erythema, Neck * 1  1/16 (6.25%)  1
Erythema, Perianal * 1  2/16 (12.50%)  2
Hyperpigmentation, Peri-Rectal * 1  1/16 (6.25%)  1
Petechiae, Eyes * 1  1/16 (6.25%)  1
Rash * 1  2/16 (12.50%)  2
Rash, Diaper * 1  1/16 (6.25%)  1
Rash, Face * 1  1/16 (6.25%)  1
Rash, Generalized * 1  1/16 (6.25%)  1
Rash, Labia * 1  1/16 (6.25%)  1
Rash, Lower Left Leg * 1  1/16 (6.25%)  1
Rash, Palms and Feet * 1  1/16 (6.25%)  1
Rash, Perineum * 1  1/16 (6.25%)  1
Rash, Scaly, Non-Erythematous * 1  1/16 (6.25%)  1
Rash, Thorax * 1  1/16 (6.25%)  1
Skin Lesion * 1  1/16 (6.25%)  1
Toxic Epidermal Necrolysis * 1  1/16 (6.25%)  1
Vascular disorders   
Bilateral Subdural hematomas * 1  1/16 (6.25%)  1
Epistaxis * 1  2/16 (12.50%)  2
Gastrointestinal Hemorrhage * 1  1/16 (6.25%)  1
Hematemesis * 1  2/16 (12.50%)  2
Hematoma, Scalp * 1  1/16 (6.25%)  1
Hematuria * 1  1/16 (6.25%)  1
Hemorrhage, Biopsy Site * 1  1/16 (6.25%)  1
Hemorrhage, Secretions from Endotracheal Tube, Respiratory Tract * 1  1/16 (6.25%)  1
Hemorrhage, Vasocath Site * 1  1/16 (6.25%)  1
Petechiae, Lower Extremity * 1  1/16 (6.25%)  1
Capillary Leak Syndrome * 1  1/16 (6.25%)  1
Engraftment Syndrome * 1  2/16 (12.50%)  2
Abdominal Compartment Syndrome * 1  1/16 (6.25%)  1
Systemic Inflammatory Response Syndrome * 1  1/16 (6.25%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (2.0)
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.
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
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 )
First Submitted: September 1, 2005
First Posted: September 5, 2005
Results First Submitted: June 8, 2015
Results First Posted: December 14, 2015
Last Update Posted: June 19, 2017