Trial Outcomes & Findings for Haploidentical Transplant for People With Chronic Granulomatous Disease Using Post Transplant Cyclophosphamide (NCT NCT02282904)
NCT ID: NCT02282904
Last Updated: 2020-05-12
Results Overview
Patient will have donor chimerism of greater than 20% and resolution of infection or autoimmunity at end of follow up
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
7 participants
Primary outcome timeframe
5 years
Results posted on
2020-05-12
Participant Flow
Participant milestones
| Measure |
CGD Recipient
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 Study
STARTED
|
7
|
|
Overall Study
COMPLETED
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Haploidentical Transplant for People With Chronic Granulomatous Disease Using Post Transplant Cyclophosphamide
Baseline characteristics by cohort
| Measure |
CGD Recipient
n=7 Participants
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
|
|---|---|
|
Age, Categorical
<=18 years
|
3 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
|
Age, Continuous
|
19.42 years
STANDARD_DEVIATION 4.8 • n=99 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
2 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
6 Participants
n=99 Participants
|
|
Region of Enrollment
India
|
1 Participants
n=99 Participants
|
|
Infection present
|
3 Participants
n=99 Participants
|
|
Autoimmunity present
|
4 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 5 yearsPatient will have donor chimerism of greater than 20% and resolution of infection or autoimmunity at end of follow up
Outcome measures
| Measure |
CGD Recipient
n=7 Participants
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
|
|---|---|
|
To Determine the Efficacy of This Allogeneic Transplant Approach in Reconstituting Normal Hematopoiesis and Reversing the Clinical Phenotype of CGD
Greater than 20% donor chimerism
|
7 Participants
|
|
To Determine the Efficacy of This Allogeneic Transplant Approach in Reconstituting Normal Hematopoiesis and Reversing the Clinical Phenotype of CGD
Resolution of inflammation or infection
|
7 Participants
|
SECONDARY outcome
Timeframe: 1 year post transplant1\. 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.
Outcome measures
| Measure |
CGD Recipient
n=7 Participants
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
|
|---|---|
|
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.
Number of patients with stable chimerism at 1 year
|
6 Participants
|
|
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.
Patients with normal DHR at 1 year
|
6 Participants
|
|
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.
Patients with Acute (Grade 3 or higher) GvHD
|
3 Participants
|
|
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.
Patients with Chronic GvHD
|
0 Participants
|
|
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.
Overall Survival
|
5 Participants
|
|
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.
Disease Free Survival
|
5 Participants
|
Adverse Events
CGD Recipient
Serious events: 3 serious events
Other events: 7 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
CGD Recipient
n=7 participants at risk
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
|
|---|---|
|
Immune system disorders
Severe Acute GvHD
|
42.9%
3/7 • Number of events 3 • Adverse Events were collected over 5 years (2015 to 2019)
|
|
Renal and urinary disorders
Hemorrhagic Cystitis
|
14.3%
1/7 • Number of events 1 • Adverse Events were collected over 5 years (2015 to 2019)
|
|
Blood and lymphatic system disorders
Post transplant lymphoproliferative disease
|
14.3%
1/7 • Number of events 1 • Adverse Events were collected over 5 years (2015 to 2019)
|
Other adverse events
| Measure |
CGD Recipient
n=7 participants at risk
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
|
|---|---|
|
Immune system disorders
Mild GvHD
|
100.0%
7/7 • Number of events 7 • Adverse Events were collected over 5 years (2015 to 2019)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place