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Trial record 3 of 5 for:    GATA2 deficiency

Pilot and Feasibility Study of Reduced-Intensity Hematopoietic Stem Cell Transplant for MonoMAC

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ClinicalTrials.gov Identifier: NCT00923364
Recruitment Status : Completed
First Posted : June 18, 2009
Results First Posted : November 30, 2017
Last Update Posted : November 30, 2017
Sponsor:
Information provided by (Responsible Party):
Dennis Hickstein, M.D., National Institutes of Health Clinical Center (CC)

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions: MDS
Immunodeficiency
GATA2
Interventions: Drug: Cyclophosphamide (CTX, Cytoxan)
Drug: Fludarabine(Fludara,Berlex Laboratories)
Procedure: Total Body Irradiation (TBI)
Procedure: Allogeneic Hematopoietic Stem Cell (HSC)
Drug: Equine Anti-Thymocyte Globulin

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Recipients

Hematopoietic Stem Cell Transplant for MonoMAC: 10/10 Human Leukocyte Antigen (HLA) Matched Related Donor (MRD) or Unrelated Donor (URD) Transplant. 9/10 HLA Matched Related Donor or Unrelated Donor Transplant. Haploidentical Related Donor Transplant. Umbilical Cord Blood Transplant.

Fludarabine(Fludara,Berlex Laboratories): 40 mg/m(2) intravenous (IV) (in the vein) over 30 minutes (in the vein) once daily on Days -6, -5, -4, and -3 or 30 mg/m(2) IV over 30 minutes (in the vein) once daily on Days -6, -5, -4, -3, and -2

Total Body Irradiation (TBI): 200 centigray (cGy) on Day -1 or 300 cGy on Day -1 (for 9/10 URD and Haplo patients)

Allogeneic hematopoietic stem cell (HSC): stem cell transplant

Healthy Related Donors No text entered.

Participant Flow:   Overall Study
    Recipients   Healthy Related Donors
STARTED   14   5 
COMPLETED   10   5 
NOT COMPLETED   4   0 
Death                3                0 
Did not go to transplant                1                0 



  Baseline Characteristics

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.
Data were not collected separately for donors and recipients.

Reporting Groups
  Description
Recipients and Healthy Related Donors

Hematopoietic Stem Cell Transplant for MonoMAC: 10/10 Human Leukocyte Antigen (HLA) Matched Related Donor (MRD) or Unrelated Donor (URD) Transplant. 9/10 HLA Matched Related Donor or Unrelated Donor Transplant. Haploidentical Related Donor Transplant. Umbilical Cord Blood Transplant.

Fludarabine(Fludara,Berlex Laboratories): 40 mg/m(2) intravenous (IV) (in the vein) over 30 minutes (in the vein) once daily on Days -6, -5, -4, and -3 or 30 mg/m(2) IV over 30 minutes (in the vein) once daily on Days -6, -5, -4, -3, and -2

Total Body Irradiation (TBI): 200 centigray (cGy) on Day -1 or 300 cGy on Day -1 (for 9/10 URD and Haplo patients)

Allogeneic hematopoietic stem cell (HSC): stem cell transplant Healthy related donors =5; recipients = 14.


Baseline Measures
   Recipients and Healthy Related Donors 
Overall Participants Analyzed 
[Units: Participants]
 19 
Age 
[Units: Participants]
Count of Participants
 
<=18 years      1   5.3% 
Between 18 and 65 years      18  94.7% 
>=65 years      0   0.0% 
Age 
[Units: Years]
Mean (Standard Deviation)
 30.21  (7.61) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
 
Female      11  57.9% 
Male      8  42.1% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
 
Hispanic or Latino      3  15.8% 
Not Hispanic or Latino      16  84.2% 
Unknown or Not Reported      0   0.0% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
 
American Indian or Alaska Native      0   0.0% 
Asian      2  10.5% 
Native Hawaiian or Other Pacific Islander      0   0.0% 
Black or African American      2  10.5% 
White      15  78.9% 
More than one race      0   0.0% 
Unknown or Not Reported      0   0.0% 
Region of Enrollment 
[Units: Participants]
Count of Participants
 
United States   19 


  Outcome Measures

1.  Primary:   Days to Neutrophil Engraftment   [ Time Frame: 30 days ]

Measure Type Primary
Measure Title Days to Neutrophil Engraftment
Measure Description Neutrophil engraftment is defined as a neutrophil count of >0.5 x 10(9) cells/L for 3 consecutive days.
Time Frame 30 days  

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.
10/19 analyzed:5 pts were healthy related donors, 1 pt taken off study prior to transplant & 3 pts had early deaths (before outcome measurements could be evaluated)

Reporting Groups
  Description
Recipients Only

Hematopoietic Stem Cell Transplant for MonoMAC: 10/10 Human Leukocyte Antigen (HLA) Matched Related Donor (MRD) or Unrelated Donor (URD) Transplant. 9/10 HLA Matched Related Donor or Unrelated Donor Transplant. Haploidentical Related Donor Transplant. Umbilical Cord Blood Transplant.

Fludarabine(Fludara,Berlex Laboratories): 40 mg/m(2) intravenous (IV) (in the vein) over 30 minutes (in the vein) once daily on Days -6, -5, -4, and -3 or 30 mg/m(2) IV over 30 minutes (in the vein) once daily on Days -6, -5, -4, -3, and -2 Total Body Irradiation (TBI): 200 centigray (cGy) on Day -1 or 300 cGy on Day -1 (for 9/10 URD and Haplo patients) Allogeneic hematopoietic stem cell (HSC): stem cell transplant


Measured Values
   Recipients Only 
Participants Analyzed   10 
Days to Neutrophil Engraftment 
[Units: Days]
Median (Full Range)
 12 
 (12 to 80) 

No statistical analysis provided for Days to Neutrophil Engraftment



2.  Primary:   Days to Platelet Engraftment   [ Time Frame: 30 days ]

Measure Type Primary
Measure Title Days to Platelet Engraftment
Measure Description Platelet engraftment is defined as a platelet count of >20 x 10(9) cells/L for 7 consecutive days without requiring a platelet transfusion.
Time Frame 30 days  

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.
10/19 analyzed:5 pts were healthy related donors, 1 pt taken off study prior to transplant & 3 pts had early deaths (before outcome measurements could be evaluated)

Reporting Groups
  Description
Recipients Only

Hematopoietic Stem Cell Transplant for MonoMAC: 10/10 Human Leukocyte Antigen (HLA) Matched Related Donor (MRD) or Unrelated Donor (URD) Transplant. 9/10 HLA Matched Related Donor or Unrelated Donor Transplant. Haploidentical Related Donor Transplant. Umbilical Cord Blood Transplant.

Fludarabine(Fludara,Berlex Laboratories): 40 mg/m(2) intravenous (IV) (in the vein) over 30 minutes (in the vein) once daily on Days -6, -5, -4, and -3 or 30 mg/m(2) IV over 30 minutes (in the vein) once daily on Days -6, -5, -4, -3, and -2 Total Body Irradiation (TBI): 200 centigray (cGy) on Day -1 or 300 cGy on Day -1 (for 9/10 URD and Haplo patients) Allogeneic hematopoietic stem cell (HSC): stem cell transplant


Measured Values
   Recipients Only 
Participants Analyzed   10 
Days to Platelet Engraftment 
[Units: Days]
Median (Full Range)
 30 
 (0 to 30) 

No statistical analysis provided for Days to Platelet Engraftment



3.  Secondary:   Percentage of Donor Cells at Last Follow Up in Patients With Mutations GATA Binding Protein 2 (GATA2)   [ Time Frame: 2 years ]

Measure Type Secondary
Measure Title Percentage of Donor Cells at Last Follow Up in Patients With Mutations GATA Binding Protein 2 (GATA2)
Measure Description Engraftment of donor cells was assessed using polymorphisms in regions known to contain short tandem repeats. Peripheral blood cluster of differentiation 14 (CD14+), cluster of differentiation 3 (CD3-)/cluster of differentiation 56 (CD56+), cluster of differentiation 19 (CD19+), and CD3+ subsets were isolated by flow cytometry and chimerism was assessed.
Time Frame 2 years  

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.
10/19 analyzed:5 pts were healthy related donors, 1 pt taken off study prior to transplant & 3 pts had early deaths (before outcome measurements could be evaluated)

Reporting Groups
  Description
Recipients Only

Hematopoietic Stem Cell Transplant for MonoMAC: 10/10 Human Leukocyte Antigen (HLA) Matched Related Donor (MRD) or Unrelated Donor (URD) Transplant. 9/10 HLA Matched Related Donor or Unrelated Donor Transplant. Haploidentical Related Donor Transplant. Umbilical Cord Blood Transplant.

Fludarabine(Fludara,Berlex Laboratories): 40 mg/m(2) intravenous (IV) (in the vein) over 30 minutes (in the vein) once daily on Days -6, -5, -4, and -3 or 30 mg/m(2) IV over 30 minutes (in the vein) once daily on Days -6, -5, -4, -3, and -2 Total Body Irradiation (TBI): 200 centigray (cGy) on Day -1 or 300 cGy on Day -1 (for 9/10 URD and Haplo patients) Allogeneic hematopoietic stem cell (HSC): stem cell transplant


Measured Values
   Recipients Only 
Participants Analyzed   10 
Percentage of Donor Cells at Last Follow Up in Patients With Mutations GATA Binding Protein 2 (GATA2) 
[Units: Percentage of donor cells]
Mean (Full Range)
 
Donor CD14+ cells, %   99.8 
 (99 to 100) 
Donor CD19+ cells, %   100 
 (100 to 100) 
Donor CD3-/CD56+ cells, %   99.8 
 (99 to 100) 
Donor CD3+ cells, %   97.6 
 (91 to 100) 

No statistical analysis provided for Percentage of Donor Cells at Last Follow Up in Patients With Mutations GATA Binding Protein 2 (GATA2)



4.  Secondary:   Incidence of Acute and Chronic Graft-versus-host Disease (GVHD)   [ Time Frame: 2 years ]

Measure Type Secondary
Measure Title Incidence of Acute and Chronic Graft-versus-host Disease (GVHD)
Measure Description Acute GVHD is assessed according to the 1994 Consensus Conference Grading Criteria. Chronic GVHD is assessed by the 2005 Chronic GVHD Consensus Project. GVHD can affect performance status and attack multiple organ systems such as the skin, liver, gut, mouth, eyes, joints, lung, etc. that can lead to a rash, diarrhea, metabolic changes, infection and/or death. The clinical grading of acute GVHD is grade 0 (none) to 4 (severe). Chronic GVHD is a delayed form of GVHD that may occur after day 100 post transplant.
Time Frame 2 years  

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.
10/19 analyzed:5 pts were healthy related donors, 1 pt taken off study prior to transplant & 3 pts had early deaths (before outcome measurements could be evaluated)

Reporting Groups
  Description
Recipients Only

Hematopoietic Stem Cell Transplant for MonoMAC: 10/10 Human Leukocyte Antigen (HLA) Matched Related Donor (MRD) or Unrelated Donor (URD) Transplant. 9/10 HLA Matched Related Donor or Unrelated Donor Transplant. Haploidentical Related Donor Transplant. Umbilical Cord Blood Transplant.

Fludarabine(Fludara,Berlex Laboratories): 40 mg/m(2) intravenous (IV) (in the vein) over 30 minutes (in the vein) once daily on Days -6, -5, -4, and -3 or 30 mg/m(2) IV over 30 minutes (in the vein) once daily on Days -6, -5, -4, -3, and -2 Total Body Irradiation (TBI): 200 centigray (cGy) on Day -1 or 300 cGy on Day -1 (for 9/10 URD and Haplo patients) Allogeneic hematopoietic stem cell (HSC): stem cell transplant


Measured Values
   Recipients Only 
Participants Analyzed   10 
Incidence of Acute and Chronic Graft-versus-host Disease (GVHD) 
[Units: Participants]
 
Acute   2 
Chronic   3 

No statistical analysis provided for Incidence of Acute and Chronic Graft-versus-host Disease (GVHD)



5.  Secondary:   Overall Survival   [ Time Frame: 2 years ]

Measure Type Secondary
Measure Title Overall Survival
Measure Description Overall survival is defined as date of on-study to date of death from any cause or last follow up.
Time Frame 2 years  

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.
10/19 analyzed:5 pts were healthy related donors, 1 pt taken off study prior to transplant & 3 pts had early deaths (before outcome measurements could be evaluated)

Reporting Groups
  Description
Recipients Only

Hematopoietic Stem Cell Transplant for MonoMAC: 10/10 Human Leukocyte Antigen (HLA) Matched Related Donor (MRD) or Unrelated Donor (URD) Transplant. 9/10 HLA Matched Related Donor or Unrelated Donor Transplant. Haploidentical Related Donor Transplant. Umbilical Cord Blood Transplant.

Fludarabine(Fludara,Berlex Laboratories): 40 mg/m(2) intravenous (IV) (in the vein) over 30 minutes (in the vein) once daily on Days -6, -5, -4, and -3 or 30 mg/m(2) IV over 30 minutes (in the vein) once daily on Days -6, -5, -4, -3, and -2 Total Body Irradiation (TBI): 200 centigray (cGy) on Day -1 or 300 cGy on Day -1 (for 9/10 URD and Haplo patients) Allogeneic hematopoietic stem cell (HSC): stem cell transplant


Measured Values
   Recipients Only 
Participants Analyzed   10 
Overall Survival 
[Units: Months]
Median (Full Range)
 76 
 (18 to 95) 

No statistical analysis provided for Overall Survival



6.  Secondary:   Number of Participants With Disease Free Survival   [ Time Frame: 2 years ]

Measure Type Secondary
Measure Title Number of Participants With Disease Free Survival
Measure Description Number of participants with documented evidence of disease progression following start of treatment.
Time Frame 2 years  

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.
10/19 analyzed:5pts were healthy related donors, 1 pt taken off study prior to transplant & 3 pts had early deaths (before outcome measurements could be evaluated)

Reporting Groups
  Description
Recipients Only

Hematopoietic Stem Cell Transplant for MonoMAC: 10/10 Human Leukocyte Antigen (HLA) Matched Related Donor (MRD) or Unrelated Donor (URD) Transplant. 9/10 HLA Matched Related Donor or Unrelated Donor Transplant. Haploidentical Related Donor Transplant. Umbilical Cord Blood Transplant.

Fludarabine(Fludara,Berlex Laboratories): 40 mg/m(2) intravenous (IV) (in the vein) over 30 minutes (in the vein) once daily on Days -6, -5, -4, and -3 or 30 mg/m(2) IV over 30 minutes (in the vein) once daily on Days -6, -5, -4, -3, and -2 Total Body Irradiation (TBI): 200 centigray (cGy) on Day -1 or 300 cGy on Day -1 (for 9/10 URD and Haplo patients) Allogeneic hematopoietic stem cell (HSC): stem cell transplant


Measured Values
   Recipients Only 
Participants Analyzed   10 
Number of Participants With Disease Free Survival 
[Units: Participants]
Count of Participants
 8 

No statistical analysis provided for Number of Participants With Disease Free Survival



7.  Secondary:   Number of Participants With Serious and Non-serious Adverse Events   [ Time Frame: 91 months ]

Measure Type Secondary
Measure Title Number of Participants With Serious and Non-serious Adverse Events
Measure Description Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events v3.0. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time Frame 91 months  

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.
Data were not collected separately for donors and recipients.

Reporting Groups
  Description
Recipients and Healthy Related Donors

Hematopoietic Stem Cell Transplant for MonoMAC: 10/10 Human Leukocyte Antigen (HLA) Matched Related Donor (MRD) or Unrelated Donor (URD) Transplant. 9/10 HLA Matched Related Donor or Unrelated Donor Transplant. Haploidentical Related Donor Transplant. Umbilical Cord Blood Transplant.

Fludarabine(Fludara,Berlex Laboratories): 40 mg/m(2) intravenous (IV) (in the vein) over 30 minutes (in the vein) once daily on Days -6, -5, -4, and -3 or 30 mg/m(2) IV over 30 minutes (in the vein) once daily on Days -6, -5, -4, -3, and -2 Total Body Irradiation (TBI): 200 centigray (cGy) on Day -1 or 300 cGy on Day -1 (for 9/10 URD and Haplo patients) Allogeneic hematopoietic stem cell (HSC): stem cell transplant Healthy related donors =5; recipients = 14.


Measured Values
   Recipients and Healthy Related Donors 
Participants Analyzed   19 
Number of Participants With Serious and Non-serious Adverse Events 
[Units: Participants]
Count of Participants
 16 

No statistical analysis provided for Number of Participants With Serious and Non-serious Adverse Events




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

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
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Dr. Dennis Hickstein
Organization: National Cancer Institute
phone: 301-594-1718
e-mail: hicksted@mail.nih.gov


Publications of Results:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Dennis Hickstein, M.D., National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00923364     History of Changes
Obsolete Identifiers: NCT00884923
Other Study ID Numbers: 090096
09-C-0096
First Submitted: June 17, 2009
First Posted: June 18, 2009
Results First Submitted: May 3, 2017
Results First Posted: November 30, 2017
Last Update Posted: November 30, 2017