Trial Outcomes & Findings for TBI Dose De-escalation for Fanconi Anemia (NCT NCT00352976)
NCT ID: NCT00352976
Last Updated: 2021-11-24
Results Overview
Number of participant with neutrophil recovery. Neutrophil recovery is defined as absolute neutrophil count ≥500/µL for three consecutive days
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
83 participants
Primary outcome timeframe
by day 42
Results posted on
2021-11-24
Participant Flow
Participant milestones
| Measure |
Treatment With TBI
Patients treated with total body irradiation 300 cGy, Fludarabine 35 mg/m\^2 (over 30 minutes daily for 4 days for a total dose of 140 mg/m\^2), Cyclophosphamide 10 mg/kg (2 hour infusion for 4 days for a total dose of 40 mg/kg), Bone Marrow Transplantation, Mycophenolate Mofetil 1 mg/kg(over 30 minutes every 12 hours for 5 days) , and Sirolimus.
|
|---|---|
|
Overall Study
STARTED
|
83
|
|
Overall Study
COMPLETED
|
83
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
TBI Dose De-escalation for Fanconi Anemia
Baseline characteristics by cohort
| Measure |
Treatment With TBI
n=83 Participants
Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
|
|---|---|
|
Age, Categorical
<=18 years
|
68 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
15 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
|
Sex: Female, Male
Female
|
36 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
47 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
82 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
8 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
|
6 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
66 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
3 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
80 participants
n=99 Participants
|
|
Region of Enrollment
Argentina
|
1 participants
n=99 Participants
|
|
Region of Enrollment
Canada
|
2 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: by day 42Population: 1 patient not evaluable since deceased at day 5 post transplant
Number of participant with neutrophil recovery. Neutrophil recovery is defined as absolute neutrophil count ≥500/µL for three consecutive days
Outcome measures
| Measure |
Treatment With TBI
n=82 Participants
Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
|
|---|---|
|
Number of Participant With Neutrophil Recovery
|
78 Participants
|
SECONDARY outcome
Timeframe: by day 100Regimen related toxicities (RRT) include: significant hemorrhagic cystitis, pulmonary hemorrhage, interstitial pneumonitis, GI hemorrhage, renal failure, erythroderma, and severe hepatic veno-occlusive disease
Outcome measures
| Measure |
Treatment With TBI
n=83 Participants
Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
|
|---|---|
|
Number of Participants Experiencing Grade ≥3 Regimen Related Toxicity
|
71 Participants
|
SECONDARY outcome
Timeframe: 100 daysSecondary Graft Rejection by day 100
Outcome measures
| Measure |
Treatment With TBI
n=83 Participants
Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
|
|---|---|
|
Number of Participants With Secondary Graft Failure at 100 Days
|
4 Participants
|
SECONDARY outcome
Timeframe: at 100 daysNumber of participants experiencing acute GVHD (all grades) by day 100
Outcome measures
| Measure |
Treatment With TBI
n=83 Participants
Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
|
|---|---|
|
Number of Participants Experiencing Acute Graft-versus-host Disease (GVHD)
|
15 Participants
|
SECONDARY outcome
Timeframe: at one yearNumber of participants experiencing chronic Graft Vs Host Disease by 1 year
Outcome measures
| Measure |
Treatment With TBI
n=83 Participants
Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
|
|---|---|
|
Number of Participants Experiencing Chronic GVHD
|
6 Participants
|
SECONDARY outcome
Timeframe: at one yearNumber of participants experiencing overall survival by 1 year
Outcome measures
| Measure |
Treatment With TBI
n=83 Participants
Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
|
|---|---|
|
Number of Participants Experiencing Overall Survival
|
70 Participants
|
SECONDARY outcome
Timeframe: by day 100Outcome measures
| Measure |
Treatment With TBI
n=83 Participants
Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
|
|---|---|
|
Number of Participants Experiencing Infections by Day 100
|
53 Participants
|
SECONDARY outcome
Timeframe: by day 180Outcome measures
| Measure |
Treatment With TBI
n=83 Participants
Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
|
|---|---|
|
Number of Participants Experiencing Infections by Day 180
|
55 Participants
|
SECONDARY outcome
Timeframe: by day 365Outcome measures
| Measure |
Treatment With TBI
n=83 Participants
Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
|
|---|---|
|
Number of Participants Experiencing Infections by Day 365
|
56 Participants
|
SECONDARY outcome
Timeframe: by 100 daysOutcome measures
| Measure |
Treatment With TBI
n=83 Participants
Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
|
|---|---|
|
Average Immunoglobulin G (IgG) Levels as a Measure of Immune Reconstitution After Transplant, by 100 Days
|
550.6 mg/dL
Standard Deviation 285.4
|
SECONDARY outcome
Timeframe: by 180 daysOutcome measures
| Measure |
Treatment With TBI
n=83 Participants
Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
|
|---|---|
|
Average IgG Levels as a Measure of Immune Reconstitution After Transplant, by 180 Days
|
652.9 mg/dL
Standard Deviation 305.8
|
SECONDARY outcome
Timeframe: by 365 daysOutcome measures
| Measure |
Treatment With TBI
n=83 Participants
Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
|
|---|---|
|
Average IgG Levels as a Measure of Immune Reconstitution After Transplant by 365 Days
|
724.0 mg/dL
Standard Deviation 258.0
|
SECONDARY outcome
Timeframe: by 100 daysOutcome measures
| Measure |
Treatment With TBI
n=83 Participants
Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
|
|---|---|
|
Average IgA Levels as a Measure of Immune Reconstitution After Transplant by 100 Days
|
88.0 mg/dL
Standard Deviation 59.9
|
SECONDARY outcome
Timeframe: by 180 daysOutcome measures
| Measure |
Treatment With TBI
n=83 Participants
Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
|
|---|---|
|
Average IgA Levels as a Measure of Immune Reconstitution After Transplant by 180 Days
|
98.7 mg/dL
Standard Deviation 48.8
|
SECONDARY outcome
Timeframe: by 365 daysOutcome measures
| Measure |
Treatment With TBI
n=83 Participants
Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
|
|---|---|
|
Average IgA Levels as a Measure of Immune Reconstitution After Transplant by 365 Days
|
107.2 mg/dL
Standard Deviation 57.0
|
SECONDARY outcome
Timeframe: by 100 daysOutcome measures
| Measure |
Treatment With TBI
n=83 Participants
Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
|
|---|---|
|
Average IgM Levels as a Measure of Immune Reconstitution After Transplant by 100 Days
|
71.1 mg/dL
Standard Deviation 84.2
|
SECONDARY outcome
Timeframe: by 180 daysOutcome measures
| Measure |
Treatment With TBI
n=83 Participants
Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
|
|---|---|
|
Average IgM Levels as a Measure of Immune Reconstitution After Transplant by 180 Days
|
77.0 mg/dL
Standard Deviation 60.3
|
SECONDARY outcome
Timeframe: by 365 daysOutcome measures
| Measure |
Treatment With TBI
n=83 Participants
Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
|
|---|---|
|
Average IgM Levels as a Measure of Immune Reconstitution After Transplant by 365 Days
|
82.8 mg/dL
Standard Deviation 57.9
|
Adverse Events
Treatment With TBI
Serious events: 4 serious events
Other events: 75 other events
Deaths: 13 deaths
Serious adverse events
| Measure |
Treatment With TBI
n=83 participants at risk
Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
|
|---|---|
|
Blood and lymphatic system disorders
Progressive Disease
|
1.2%
1/83 • Number of events 3 • Through after transplant by 365 Days
|
|
Blood and lymphatic system disorders
Relapsed
|
1.2%
1/83 • Number of events 2 • Through after transplant by 365 Days
|
|
Infections and infestations
Infection
|
2.4%
2/83 • Number of events 2 • Through after transplant by 365 Days
|
|
Blood and lymphatic system disorders
Blood/Bone Marrow GVHD
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Injury, poisoning and procedural complications
Graft failure
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
Other adverse events
| Measure |
Treatment With TBI
n=83 participants at risk
Patients treated with total body irradiation, Fludarabine, Cyclophosphamide, Bone Marrow Transplantation, Mycophenolate Mofetil, and Sirolimus.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Blood and lymphatic system disorders
Injury, poisoning and procedural complications, other
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Blood and lymphatic system disorders
Investigations, other
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Blood and lymphatic system disorders
Thrombosis
|
3.6%
3/83 • Number of events 5 • Through after transplant by 365 Days
|
|
Blood and lymphatic system disorders
Thrombotic thrombocytopenic purpura
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Blood and lymphatic system disorders
hemolysis
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Blood and lymphatic system disorders
hypoatremia
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Blood and lymphatic system disorders
neurotoxicity
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Cardiac disorders
cardiomegaly
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Ear and labyrinth disorders
myringotomy
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Gastrointestinal disorders
Hemorrhage
|
1.2%
1/83 • Number of events 3 • Through after transplant by 365 Days
|
|
Gastrointestinal disorders
Ileum obstruction
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Gastrointestinal disorders
Mucositis
|
4.8%
4/83 • Number of events 4 • Through after transplant by 365 Days
|
|
Gastrointestinal disorders
cholecystectomy
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Gastrointestinal disorders
hepatic steatosis
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Gastrointestinal disorders
hernia
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Gastrointestinal disorders
ischemic hepatitis
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Gastrointestinal disorders
pancreatic inflammation
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Gastrointestinal disorders
proximal obstruction
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
General disorders
multi-system failure
|
3.6%
3/83 • Number of events 3 • Through after transplant by 365 Days
|
|
Hepatobiliary disorders
Hemmorhage
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Hepatobiliary disorders
Veno-Occlusive Disease
|
3.6%
3/83 • Number of events 4 • Through after transplant by 365 Days
|
|
Immune system disorders
allergic reaction
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Infections and infestations
Herpes
|
6.0%
5/83 • Number of events 6 • Through after transplant by 365 Days
|
|
Infections and infestations
Infection
|
50.6%
42/83 • Number of events 122 • Through after transplant by 365 Days
|
|
Infections and infestations
Sepsis
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Infections and infestations
Septic shock
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Injury, poisoning and procedural complications
Engraftment Syndrome
|
10.8%
9/83 • Number of events 9 • Through after transplant by 365 Days
|
|
Injury, poisoning and procedural complications
GI bleed
|
15.7%
13/83 • Number of events 15 • Through after transplant by 365 Days
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications, other
|
2.4%
2/83 • Number of events 2 • Through after transplant by 365 Days
|
|
Investigations
Investigations, other
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Metabolism and nutrition disorders
Anorexia
|
2.4%
2/83 • Number of events 2 • Through after transplant by 365 Days
|
|
Metabolism and nutrition disorders
Type 2 Diabetes
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Metabolism and nutrition disorders
hyperglycemia
|
7.2%
6/83 • Number of events 6 • Through after transplant by 365 Days
|
|
Nervous system disorders
altered mental status
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Nervous system disorders
intracranial hemorrhage
|
2.4%
2/83 • Number of events 2 • Through after transplant by 365 Days
|
|
Nervous system disorders
neurotoxicity
|
2.4%
2/83 • Number of events 3 • Through after transplant by 365 Days
|
|
Nervous system disorders
vision impairment
|
3.6%
3/83 • Number of events 3 • Through after transplant by 365 Days
|
|
Renal and urinary disorders
Acute kidney injury
|
2.4%
2/83 • Number of events 2 • Through after transplant by 365 Days
|
|
Renal and urinary disorders
Cystitis
|
31.3%
26/83 • Number of events 30 • Through after transplant by 365 Days
|
|
Renal and urinary disorders
Dialysis
|
7.2%
6/83 • Number of events 7 • Through after transplant by 365 Days
|
|
Renal and urinary disorders
Injury, poisoning and procedural complications, other
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Respiratory, thoracic and mediastinal disorders
Drug Toxicity
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Respiratory, thoracic and mediastinal disorders
Intubation
|
13.3%
11/83 • Number of events 14 • Through after transplant by 365 Days
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
37.3%
31/83 • Number of events 74 • Through after transplant by 365 Days
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Hemorrhage
|
8.4%
7/83 • Number of events 7 • Through after transplant by 365 Days
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Respiratory, thoracic and mediastinal disorders
Respirtory distress syndrome
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Respiratory, thoracic and mediastinal disorders
Sinusitis
|
8.4%
7/83 • Number of events 9 • Through after transplant by 365 Days
|
|
Respiratory, thoracic and mediastinal disorders
bilateral interstitial lung disease
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Respiratory, thoracic and mediastinal disorders
epistaxis
|
1.2%
1/83 • Number of events 2 • Through after transplant by 365 Days
|
|
Respiratory, thoracic and mediastinal disorders
pnuemothorax
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Respiratory, thoracic and mediastinal disorders
pulmonary cytolytic thrombi
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Skin and subcutaneous tissue disorders
Drug Toxicity
|
3.6%
3/83 • Number of events 3 • Through after transplant by 365 Days
|
|
Vascular disorders
Hypertension
|
28.9%
24/83 • Number of events 26 • Through after transplant by 365 Days
|
|
Vascular disorders
Neuropathy
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Vascular disorders
hypotension
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Cardiac disorders
Hemorrhage
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Cardiac disorders
Pericardial Effusion
|
13.3%
11/83 • Number of events 13 • Through after transplant by 365 Days
|
|
Cardiac disorders
atrial fibrilation
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Cardiac disorders
cardiac arrest
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Cardiac disorders
cardiomyopathy
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
|
Cardiac disorders
edema
|
1.2%
1/83 • Number of events 1 • Through after transplant by 365 Days
|
Additional Information
Margaret L. MacMillan, M.D.
Masonic Cancer Center, University of Minnesota
Phone: 612-626-2961
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place