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Haploidentical Transplant for People With Chronic Granulomatous Disease Using Post Transplant Cyclophosphamide

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: NCT02282904
Recruitment Status : Terminated
First Posted : November 5, 2014
Results First Posted : May 1, 2020
Last Update Posted : May 12, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Chronic Granulomatous Disease
Interventions Drug: Sirolimus
Biological: Donor peripheral blood stem cells.
Drug: Cyclophosphamide post transplant
Radiation: Total body 200cGy
Drug: Cyclophosphamide
Drug: Fludarabine
Drug: Busulfan
Enrollment 7
Recruitment Details  
Pre-assignment Details  
Arm/Group Title CGD Recipient
Hide Arm/Group Description

CGD patients that will undergo haplo transplantation with post-transplant cyclophosphamide as described

Sirolimus: For pediatric patients: Begin sirolimus 1 mg/m2 PO q4h for 3 doses, then 1 mg/m2 once a day (QD). For adult patients, begin sirolimus 5 mg PO q4h for 3 doses, then 5 mg once a day (QD).

Doses may be adjusted to maintain trough levels between 8-14 ng/ml. Recipients will take sirolimus from Day +5 to at least Day 100 (minimum).

Donor peripheral blood stem cells.: Infuse donor graft.

Cyclophosphamide post transplant: 50 mg/kg/d IV infused over 90 minutes. Day +3 and +4

Total body 200cGy: Day -1

Cyclophosphamide: 14.5 mg/kg IV over one hour Day -6 and -5

Fludarabine: 30 mg/m2 over 30 minutes Day -6 through Day -2

Busulfan: Busulfan 3.2 mg/kg IV once daily over 2-3 hours Day -4,-3,-2

Period Title: Overall Study
Started 7
Completed 7 [1]
Not Completed 0
[1]
Patient accrual was stopped early, and the protocol closed after completing followup
Arm/Group Title CGD Recipient
Hide Arm/Group Description

CGD patients that will undergo haplo transplantation with post-transplant cyclophosphamide as described

Sirolimus: For pediatric patients: Begin sirolimus 1 mg/m2 PO q4h for 3 doses, then 1 mg/m2 once a day (QD). For adult patients, begin sirolimus 5 mg PO q4h for 3 doses, then 5 mg once a day (QD).

Doses may be adjusted to maintain trough levels between 8-14 ng/ml. Recipients will take sirolimus from Day +5 to at least Day 100 (minimum).

Donor peripheral blood stem cells.: Infuse donor graft.

Cyclophosphamide post transplant: 50 mg/kg/d IV infused over 90 minutes. Day +3 and +4

Total body 200cGy: Day -1

Cyclophosphamide: 14.5 mg/kg IV over one hour Day -6 and -5

Fludarabine: 30 mg/m2 over 30 minutes Day -6 through Day -2

Busulfan: Busulfan 3.2 mg/kg IV once daily over 2-3 hours Day -4,-3,-2

Overall Number of Baseline Participants 7
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants
<=18 years
3
  42.9%
Between 18 and 65 years
4
  57.1%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 7 participants
19.42  (4.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants
Female
2
  28.6%
Male
5
  71.4%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants
American Indian or Alaska Native
0
   0.0%
Asian
2
  28.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
2
  28.6%
More than one race
1
  14.3%
Unknown or Not Reported
2
  28.6%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants
United States
6
  85.7%
India
1
  14.3%
Infection present  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants
3
  42.9%
Autoimmunity present  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants
4
  57.1%
1.Primary Outcome
Title To Determine the Efficacy of This Allogeneic Transplant Approach in Reconstituting Normal Hematopoiesis and Reversing the Clinical Phenotype of CGD
Hide Description Patient will have donor chimerism of greater than 20% and resolution of infection or autoimmunity at end of follow up
Time Frame 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title CGD Recipient
Hide Arm/Group Description:

CGD patients that will undergo haplo transplantation with post-transplant cyclophosphamide as described

Sirolimus: For pediatric patients: Begin sirolimus 1 mg/m2 PO q4h for 3 doses, then 1 mg/m2 once a day (QD). For adult patients, begin sirolimus 5 mg PO q4h for 3 doses, then 5 mg once a day (QD).

Doses may be adjusted to maintain trough levels between 8-14 ng/ml. Recipients will take sirolimus from Day +5 to at least Day 100 (minimum).

Donor peripheral blood stem cells.: Infuse donor graft.

Cyclophosphamide post transplant: 50 mg/kg/d IV infused over 90 minutes. Day +3 and +4

Total body 200cGy: Day -1

Cyclophosphamide: 14.5 mg/kg IV over one hour Day -6 and -5

Fludarabine: 30 mg/m2 over 30 minutes Day -6 through Day -2

Busulfan: Busulfan 3.2 mg/kg IV once daily over 2-3 hours Day -4,-3,-2

Overall Number of Participants Analyzed 7
Measure Type: Count of Participants
Unit of Measure: Participants
Greater than 20% donor chimerism
7
 100.0%
Resolution of inflammation or infection
7
 100.0%
2.Secondary Outcome
Title To Determine the Safety of This Allogeneic HSCT Approach in Patients With CGD Including Transplant Related Toxicity, the Incidence of Acute and Chronic Graft-versus-host Disease, Immune Reconstitution, Overalland Disease-free Survival.
Hide Description 1. Stable chimerism as indicated by 30-50% myeloid engraftment and 50% lymphoid engraftment as assessed by 1 year post transplant. 2. Immune reconstitution levels with DHR as a marker of normal neutrophil function by 1 year post transplant. 3. GvHD grades of less than 3.
Time Frame 1 year post transplant
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title CGD Recipient
Hide Arm/Group Description:

CGD patients that will undergo haplo transplantation with post-transplant cyclophosphamide as described

Sirolimus: For pediatric patients: Begin sirolimus 1 mg/m2 PO q4h for 3 doses, then 1 mg/m2 once a day (QD). For adult patients, begin sirolimus 5 mg PO q4h for 3 doses, then 5 mg once a day (QD).

Doses may be adjusted to maintain trough levels between 8-14 ng/ml. Recipients will take sirolimus from Day +5 to at least Day 100 (minimum).

Donor peripheral blood stem cells.: Infuse donor graft.

Cyclophosphamide post transplant: 50 mg/kg/d IV infused over 90 minutes. Day +3 and +4

Total body 200cGy: Day -1

Cyclophosphamide: 14.5 mg/kg IV over one hour Day -6 and -5

Fludarabine: 30 mg/m2 over 30 minutes Day -6 through Day -2

Busulfan: Busulfan 3.2 mg/kg IV once daily over 2-3 hours Day -4,-3,-2

Overall Number of Participants Analyzed 7
Measure Type: Count of Participants
Unit of Measure: Participants
Number of patients with stable chimerism at 1 year
6
  85.7%
Patients with normal DHR at 1 year
6
  85.7%
Patients with Acute (Grade 3 or higher) GvHD
3
  42.9%
Patients with Chronic GvHD
0
   0.0%
Overall Survival
5
  71.4%
Disease Free Survival
5
  71.4%
Time Frame Adverse Events were collected over 5 years (2015 to 2019)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title CGD Recipient
Hide Arm/Group Description

CGD patients that will undergo haplo transplantation with post-transplant cyclophosphamide as described

Sirolimus: For pediatric patients: Begin sirolimus 1 mg/m2 PO q4h for 3 doses, then 1 mg/m2 once a day (QD). For adult patients, begin sirolimus 5 mg PO q4h for 3 doses, then 5 mg once a day (QD).

Doses may be adjusted to maintain trough levels between 8-14 ng/ml. Recipients will take sirolimus from Day +5 to at least Day 100 (minimum).

Donor peripheral blood stem cells.: Infuse donor graft.

Cyclophosphamide post transplant: 50 mg/kg/d IV infused over 90 minutes. Day +3 and +4

Total body 200cGy: Day -1

Cyclophosphamide: 14.5 mg/kg IV over one hour Day -6 and -5

Fludarabine: 30 mg/m2 over 30 minutes Day -6 through Day -2

Busulfan: Busulfan 3.2 mg/kg IV once daily over 2-3 hours Day -4,-3,-2

All-Cause Mortality
CGD Recipient
Affected / at Risk (%)
Total   2/7 (28.57%)    
Hide Serious Adverse Events
CGD Recipient
Affected / at Risk (%) # Events
Total   3/7 (42.86%)    
Blood and lymphatic system disorders   
Post transplant lymphoproliferative disease  [1]  1/7 (14.29%)  1
Immune system disorders   
Severe Acute GvHD   3/7 (42.86%)  3
Renal and urinary disorders   
Hemorrhagic Cystitis  [2]  1/7 (14.29%)  1
Indicates events were collected by systematic assessment
[1]
Development of a clonal outgrowth of cells due to suppression of the immune system
[2]
Development of irritation and bleeding from the bladder due to infection and/or chemotherapy
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
CGD Recipient
Affected / at Risk (%) # Events
Total   7/7 (100.00%)    
Immune system disorders   
Mild GvHD   7/7 (100.00%)  7
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Elizabeth Kang
Organization: NIAID
Phone: 3014027567
EMail: ekang@niaid.nih.gov
Layout table for additonal information
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier: NCT02282904    
Other Study ID Numbers: 150007
15-I-0007 ( Other Identifier: NIH )
First Submitted: November 4, 2014
First Posted: November 5, 2014
Results First Submitted: April 13, 2020
Results First Posted: May 1, 2020
Last Update Posted: May 12, 2020