Trial Outcomes & Findings for Early Administration of ATG Followed by Cyclophosphamide, Busulfan and Fludarabine Before a Donor Stem Cell Transplant in Patients With Hematological Cancer (NCT NCT00787761)
NCT ID: NCT00787761
Last Updated: 2012-10-01
Results Overview
Chimerism analysis of peripheral blood mononuclear cells using PCR for STR/VNTR will be performed post transplant. On each occasion, the peripheral blood will be separated into the T-cell component (using e.g. CD3 selection) and the myeloid component (using e.g.CD14/15 selection) before assessment of chimerism.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
24 participants
Primary outcome timeframe
Day 30
Results posted on
2012-10-01
Participant Flow
24 patients were enrolled between 4/20/2007 and 5/3/2010. Patients who were undergoing transplant at Northside Hospital were potentially eligible.
29 patients signed consent for this study. 2 patients were initially screen failures but eventually were determined eligible \& were treated on study. 1 patient was considered a screen failure due to having an ineligible donor. One patient had progressive disease and one patient had compliance-related issues prohibiting them from particiapting.
Participant milestones
| Measure |
RIC Transplant Using ATG, Busulfan, Fludarabine and Cytoxan
All patients received ATG 1mg/kg Day-16 and then 3.5 mg/kg Day -15 Fludarabine 30mg/m2/day on days -7 to -3 Busulfan 130 mg/m2 on days -4 \& -3 Cyclophosphamide 1.5 g/m2 on day -2 Tacrolimus begins 0.03mg/kg bid on Day -1 Stem Cell transplant on Day 0 Methotrexate 5mg/m2 given D+1, +3 and +6
|
|---|---|
|
Overall Study
STARTED
|
24
|
|
Overall Study
COMPLETED
|
24
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Early Administration of ATG Followed by Cyclophosphamide, Busulfan and Fludarabine Before a Donor Stem Cell Transplant in Patients With Hematological Cancer
Baseline characteristics by cohort
| Measure |
RIC Transplant Using ATG, Busulfan, Fludarabine and Cytoxan
n=24 Participants
All patients received ATG 1mg/kg Day-16 and then 3.5 mg/kg Day -15 Fludarabine 30mg/m2/day on days -7 to -3 Busulfan 130 mg/m2 on days -4 \& -3 Cyclophosphamide 1.5 g/m2 on day -2 Tacrolimus begins 0.03mg/kg bid on Day -1 Stem Cell transplant on Day 0 Methotrexate 5mg/m2 given D+1, +3 and +6
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
20 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
4 Participants
n=5 Participants
|
|
Age Continuous
|
54.5 years
STANDARD_DEVIATION 11.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
24 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 30Population: only 15 of the patients treated on study had Day 30 chimerism results.
Chimerism analysis of peripheral blood mononuclear cells using PCR for STR/VNTR will be performed post transplant. On each occasion, the peripheral blood will be separated into the T-cell component (using e.g. CD3 selection) and the myeloid component (using e.g.CD14/15 selection) before assessment of chimerism.
Outcome measures
| Measure |
Transplant Recipients
n=15 Participants
patients receiving transplant using ATG/Bu/Flu/Cy per this protocol
|
|---|---|
|
Achievement of > 90% (Full) Donor Chimerism in the T-cell Lineage as Measured by PCR at Day 30 Post-transplantation
|
12 participants
|
SECONDARY outcome
Timeframe: Day 90Population: 20 of the patients treated on this study had Day 90 chimerism drawn.
Chimerism analysis of peripheral blood mononuclear cells using PCR for STR/VNTR will be performed post transplant. On each occasion, the peripheral blood will be separated into the T-cell component (using e.g. CD3 selection) and the myeloid component (using e.g.CD14/15 selection) before assessment of chimerism.
Outcome measures
| Measure |
Transplant Recipients
n=20 Participants
patients receiving transplant using ATG/Bu/Flu/Cy per this protocol
|
|---|---|
|
T-cell and Myeloid Chimerism at Days 90 Post-transplantation (>90% Chimerism)
|
17 participants
|
SECONDARY outcome
Timeframe: 180 daysPopulation: 20 of the patients treated on study had chimerism drawn on day 180.
Chimerism analysis of peripheral blood mononuclear cells using PCR for STR/VNTR will be performed post transplant. On each occasion, the peripheral blood will be separated into the T-cell component (using e.g. CD3 selection) and the myeloid component (using e.g.CD14/15 selection) before assessment of chimerism.
Outcome measures
| Measure |
Transplant Recipients
n=20 Participants
patients receiving transplant using ATG/Bu/Flu/Cy per this protocol
|
|---|---|
|
T-cell and Myeloid Chimerism at Days 180 Post-transplantation (>90%)
|
19 participants
|
SECONDARY outcome
Timeframe: Day 100Population: 23 patients were able to be analyzed for severe gvhd
number of patients who experienced post-transplant complication (GVHD) as seen by clinical evidence including but not limited to skin rash, elevated liver function tests, nausea/vomiting/diarrhea.
Outcome measures
| Measure |
Transplant Recipients
n=23 Participants
patients receiving transplant using ATG/Bu/Flu/Cy per this protocol
|
|---|---|
|
Number of Patients Who Experience Severe (Grade 3 or 4) Acute Graft-versus-host Disease
|
2 participants
Interval 0.0 to 20.0
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: 23 patients were able to be analyzed for severe gvhd
Patients who had post-transplant complication (GVHD) as seen by clinical evidence including but not limited to skin rash, elevated liver function tests, nausea/vomiting/diarrhea.
Outcome measures
| Measure |
Transplant Recipients
n=23 Participants
patients receiving transplant using ATG/Bu/Flu/Cy per this protocol
|
|---|---|
|
Number of Patients Experiencing Extensive Chronic Graft Versus Host Disease (GVHD)
|
13 participants
|
SECONDARY outcome
Timeframe: Day 180Population: 23 patients were able to be analyzed for NRM at 180 days
non-relapse mortality refers to the death of a patient for causes other than relapsed disease.
Outcome measures
| Measure |
Transplant Recipients
n=23 Participants
patients receiving transplant using ATG/Bu/Flu/Cy per this protocol
|
|---|---|
|
Non-relapse Mortality (NRM) at Day 180 Post-transplantation
|
0 participants
|
SECONDARY outcome
Timeframe: 24 monthsPopulation: 23 patients were able to be analyzed for DFS at 24 months
Disease Free survival is measured by the amount of time a patient spends in a disease free state after being transplanted.
Outcome measures
| Measure |
Transplant Recipients
n=23 Participants
patients receiving transplant using ATG/Bu/Flu/Cy per this protocol
|
|---|---|
|
Disease-free Survival (DFS) at 24 Months
|
13 participants
Interval 31.0 to 72.0
|
SECONDARY outcome
Timeframe: 24 monthsPopulation: 23 patients were able to be analyzed for OS at 24 months
Overall survival refers to the length of time a patient is alive after transplant regardless of whether they have progressive or relapsed disease.
Outcome measures
| Measure |
Transplant Recipients
n=23 Participants
patients receiving transplant using ATG/Bu/Flu/Cy per this protocol
|
|---|---|
|
Overall Survival (OS) at 24 Months
|
16 participants
Interval 43.0 to 83.0
|
Adverse Events
RIC Transplant Using ATG, Busulfan, Fludarabine and Cytoxan
Serious events: 13 serious events
Other events: 24 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
RIC Transplant Using ATG, Busulfan, Fludarabine and Cytoxan
n=24 participants at risk
All patients received ATG 1mg/kg Day-16 and then 3.5 mg/kg Day -15 Fludarabine 30mg/m2/day on days -7 to -3 Busulfan 130 mg/m2 on days -4 \& -3 Cyclophosphamide 1.5 g/m2 on day -2 Tacrolimus begins 0.03mg/kg bid on Day -1 Stem Cell transplant on Day 0 Methotrexate 5mg/m2 given D+1, +3 and +6
|
|---|---|
|
Gastrointestinal disorders
Abdominal Abcess
|
4.2%
1/24 • Number of events 1
|
|
Cardiac disorders
Cardiac Tamponade
|
4.2%
1/24 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
4.2%
1/24 • Number of events 1
|
|
General disorders
Fever
|
12.5%
3/24 • Number of events 3
|
|
General disorders
Chemotherapy reaction
|
4.2%
1/24 • Number of events 1
|
|
General disorders
Death
|
16.7%
4/24 • Number of events 4
|
|
Renal and urinary disorders
Acute Renal Failure
|
4.2%
1/24 • Number of events 1
|
|
Hepatobiliary disorders
Cholecystitis
|
4.2%
1/24 • Number of events 1
|
|
Gastrointestinal disorders
GI Bleeding
|
4.2%
1/24 • Number of events 1
|
|
General disorders
hospitalization for high dose steroid management
|
4.2%
1/24 • Number of events 1
|
|
Nervous system disorders
Altered Mental Status
|
4.2%
1/24 • Number of events 1
|
Other adverse events
| Measure |
RIC Transplant Using ATG, Busulfan, Fludarabine and Cytoxan
n=24 participants at risk
All patients received ATG 1mg/kg Day-16 and then 3.5 mg/kg Day -15 Fludarabine 30mg/m2/day on days -7 to -3 Busulfan 130 mg/m2 on days -4 \& -3 Cyclophosphamide 1.5 g/m2 on day -2 Tacrolimus begins 0.03mg/kg bid on Day -1 Stem Cell transplant on Day 0 Methotrexate 5mg/m2 given D+1, +3 and +6
|
|---|---|
|
Gastrointestinal disorders
abdominal cramping
|
29.2%
7/24 • Number of events 7
|
|
Gastrointestinal disorders
abdominal distension
|
20.8%
5/24 • Number of events 5
|
|
Gastrointestinal disorders
abdominal pain
|
45.8%
11/24 • Number of events 11
|
|
Social circumstances
agitation
|
16.7%
4/24 • Number of events 4
|
|
Metabolism and nutrition disorders
Alk Phos
|
75.0%
18/24 • Number of events 18
|
|
Metabolism and nutrition disorders
ALT
|
70.8%
17/24 • Number of events 17
|
|
Nervous system disorders
altered mental status
|
8.3%
2/24 • Number of events 2
|
|
Blood and lymphatic system disorders
ANC
|
91.7%
22/24 • Number of events 22
|
|
Blood and lymphatic system disorders
anemia
|
87.5%
21/24 • Number of events 21
|
|
Gastrointestinal disorders
anorexia/decreased appetite
|
70.8%
17/24 • Number of events 17
|
|
Social circumstances
anxiety
|
79.2%
19/24 • Number of events 19
|
|
Musculoskeletal and connective tissue disorders
arthralgia
|
12.5%
3/24 • Number of events 3
|
|
Metabolism and nutrition disorders
AST
|
75.0%
18/24 • Number of events 18
|
|
Musculoskeletal and connective tissue disorders
back pain
|
41.7%
10/24 • Number of events 10
|
|
Infections and infestations
BK virus
|
12.5%
3/24 • Number of events 3
|
|
Blood and lymphatic system disorders
blood in stool
|
12.5%
3/24 • Number of events 3
|
|
Eye disorders
blurred vision
|
20.8%
5/24 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
bone pain
|
20.8%
5/24 • Number of events 5
|
|
Infections and infestations
Clostridium difficile
|
8.3%
2/24 • Number of events 2
|
|
Cardiac disorders
Chest discomfort
|
8.3%
2/24 • Number of events 2
|
|
Cardiac disorders
chest tightness
|
16.7%
4/24 • Number of events 4
|
|
Cardiac disorders
chest wall pain
|
16.7%
4/24 • Number of events 4
|
|
General disorders
chills
|
70.8%
17/24 • Number of events 17
|
|
Infections and infestations
CMV
|
16.7%
4/24 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
coarse breath sounds
|
8.3%
2/24 • Number of events 2
|
|
Nervous system disorders
confusion
|
16.7%
4/24 • Number of events 4
|
|
Gastrointestinal disorders
constipation
|
37.5%
9/24 • Number of events 9
|
|
Respiratory, thoracic and mediastinal disorders
cough
|
66.7%
16/24 • Number of events 16
|
|
Renal and urinary disorders
creatinine
|
50.0%
12/24 • Number of events 12
|
|
Surgical and medical procedures
Central venous catheter (CVC) discomfort
|
33.3%
8/24 • Number of events 8
|
|
Skin and subcutaneous tissue disorders
CVC erythema
|
8.3%
2/24 • Number of events 2
|
|
Metabolism and nutrition disorders
dehydration
|
12.5%
3/24 • Number of events 3
|
|
Nervous system disorders
depression
|
45.8%
11/24 • Number of events 11
|
|
Nervous system disorders
diaphoresis
|
8.3%
2/24 • Number of events 2
|
|
Gastrointestinal disorders
diarrhea
|
87.5%
21/24 • Number of events 21
|
|
Respiratory, thoracic and mediastinal disorders
diminished breath sounds
|
8.3%
2/24 • Number of events 2
|
|
General disorders
dizziness
|
37.5%
9/24 • Number of events 9
|
|
General disorders
drowsy
|
29.2%
7/24 • Number of events 7
|
|
Eye disorders
dry eye
|
12.5%
3/24 • Number of events 3
|
|
Gastrointestinal disorders
dry mouth
|
12.5%
3/24 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
dry skin
|
29.2%
7/24 • Number of events 7
|
|
Gastrointestinal disorders
dysphagia
|
25.0%
6/24 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
dyspnea
|
70.8%
17/24 • Number of events 17
|
|
Renal and urinary disorders
dysuria
|
29.2%
7/24 • Number of events 7
|
|
Blood and lymphatic system disorders
edema
|
66.7%
16/24 • Number of events 16
|
|
Skin and subcutaneous tissue disorders
erythema
|
29.2%
7/24 • Number of events 7
|
|
Eye disorders
eye irritation
|
8.3%
2/24 • Number of events 2
|
|
Eye disorders
eye redness
|
8.3%
2/24 • Number of events 2
|
|
General disorders
Facial flushing
|
25.0%
6/24 • Number of events 6
|
|
Musculoskeletal and connective tissue disorders
fall
|
8.3%
2/24 • Number of events 2
|
|
General disorders
fatigue
|
79.2%
19/24 • Number of events 19
|
|
General disorders
fever
|
83.3%
20/24 • Number of events 20
|
|
Nervous system disorders
flat affect
|
12.5%
3/24 • Number of events 3
|
|
Gastrointestinal disorders
flatulence
|
12.5%
3/24 • Number of events 3
|
|
Infections and infestations
folliculitis
|
12.5%
3/24 • Number of events 3
|
|
General disorders
generalized pain
|
29.2%
7/24 • Number of events 7
|
|
Gastrointestinal disorders
Gastroesophogeal Reflux disease (GERD)
|
83.3%
20/24 • Number of events 20
|
|
General disorders
headache
|
87.5%
21/24 • Number of events 21
|
|
Renal and urinary disorders
hematuria
|
8.3%
2/24 • Number of events 2
|
|
Gastrointestinal disorders
hemorrhoids
|
8.3%
2/24 • Number of events 2
|
|
General disorders
hiccups
|
8.3%
2/24 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
hip pain
|
8.3%
2/24 • Number of events 2
|
|
Hepatobiliary disorders
hyperbilirubinemia
|
41.7%
10/24 • Number of events 10
|
|
General disorders
hyperglycemia
|
83.3%
20/24 • Number of events 20
|
|
Metabolism and nutrition disorders
hyperkalemia
|
75.0%
18/24 • Number of events 18
|
|
Metabolism and nutrition disorders
hypermagnesemia
|
83.3%
20/24 • Number of events 20
|
|
Metabolism and nutrition disorders
hypernatremia
|
20.8%
5/24 • Number of events 5
|
|
Metabolism and nutrition disorders
hyperphosphatemia
|
8.3%
2/24 • Number of events 2
|
|
Cardiac disorders
hypertension
|
41.7%
10/24 • Number of events 10
|
|
Metabolism and nutrition disorders
hypoalbuminemia
|
95.8%
23/24 • Number of events 23
|
|
Metabolism and nutrition disorders
hypocalcemia
|
79.2%
19/24 • Number of events 19
|
|
Metabolism and nutrition disorders
hypoglycemia
|
20.8%
5/24 • Number of events 5
|
|
Metabolism and nutrition disorders
hypokalemia
|
75.0%
18/24 • Number of events 18
|
|
Metabolism and nutrition disorders
hypomagnesemia
|
83.3%
20/24 • Number of events 20
|
|
Metabolism and nutrition disorders
hyponatremia
|
75.0%
18/24 • Number of events 18
|
|
Metabolism and nutrition disorders
hypophosphatemia
|
16.7%
4/24 • Number of events 4
|
|
Cardiac disorders
hypotension
|
16.7%
4/24 • Number of events 4
|
|
Endocrine disorders
hypothyroidism
|
8.3%
2/24 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
hypoxia
|
8.3%
2/24 • Number of events 2
|
|
General disorders
insomnia
|
41.7%
10/24 • Number of events 10
|
|
Musculoskeletal and connective tissue disorders
joint pain
|
12.5%
3/24 • Number of events 3
|
|
General disorders
lethargy
|
16.7%
4/24 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
lip lesion
|
8.3%
2/24 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
lower extremity pain
|
25.0%
6/24 • Number of events 6
|
|
Infections and infestations
MRSE
|
16.7%
4/24 • Number of events 4
|
|
Gastrointestinal disorders
mucositis
|
45.8%
11/24 • Number of events 11
|
|
Musculoskeletal and connective tissue disorders
myalgia
|
16.7%
4/24 • Number of events 4
|
|
Gastrointestinal disorders
nausea
|
91.7%
22/24 • Number of events 22
|
|
Musculoskeletal and connective tissue disorders
neck pain
|
12.5%
3/24 • Number of events 3
|
|
General disorders
night sweats
|
20.8%
5/24 • Number of events 5
|
|
Renal and urinary disorders
nocturia
|
12.5%
3/24 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
numbness
|
16.7%
4/24 • Number of events 4
|
|
Gastrointestinal disorders
oral sensitivity
|
29.2%
7/24 • Number of events 7
|
|
Skin and subcutaneous tissue disorders
Peeling of skin
|
8.3%
2/24 • Number of events 2
|
|
Blood and lymphatic system disorders
petechiae
|
12.5%
3/24 • Number of events 3
|
|
Infections and infestations
pneumonia
|
8.3%
2/24 • Number of events 2
|
|
Gastrointestinal disorders
poor appetite
|
12.5%
3/24 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
post-nasal drip
|
16.7%
4/24 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
prurutis
|
45.8%
11/24 • Number of events 11
|
|
Skin and subcutaneous tissue disorders
rash
|
45.8%
11/24 • Number of events 11
|
|
General disorders
restless
|
8.3%
2/24 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
rhinorrhea
|
16.7%
4/24 • Number of events 4
|
|
General disorders
rigors
|
66.7%
16/24 • Number of events 16
|
|
Respiratory, thoracic and mediastinal disorders
seasonal allergies
|
12.5%
3/24 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
shoulder pain
|
8.3%
2/24 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
sinus congestion
|
33.3%
8/24 • Number of events 8
|
|
Skin and subcutaneous tissue disorders
skin tenderness
|
8.3%
2/24 • Number of events 2
|
|
Blood and lymphatic system disorders
swelling (hands and fingers)
|
8.3%
2/24 • Number of events 2
|
|
Cardiac disorders
tachycradia
|
37.5%
9/24 • Number of events 9
|
|
Gastrointestinal disorders
taste alteration
|
12.5%
3/24 • Number of events 3
|
|
Gastrointestinal disorders
throat pain
|
20.8%
5/24 • Number of events 5
|
|
Blood and lymphatic system disorders
thrombocytopenia
|
95.8%
23/24 • Number of events 23
|
|
Infections and infestations
thrush
|
12.5%
3/24 • Number of events 3
|
|
Nervous system disorders
tremors
|
20.8%
5/24 • Number of events 5
|
|
Nervous system disorders
unsteadiness
|
12.5%
3/24 • Number of events 3
|
|
Renal and urinary disorders
urinary frequency
|
33.3%
8/24 • Number of events 8
|
|
Renal and urinary disorders
urinary hesitancy
|
12.5%
3/24 • Number of events 3
|
|
Renal and urinary disorders
urinary incontinence
|
12.5%
3/24 • Number of events 3
|
|
Renal and urinary disorders
urinary urgency
|
12.5%
3/24 • Number of events 3
|
|
Gastrointestinal disorders
vomiting
|
83.3%
20/24 • Number of events 20
|
|
Blood and lymphatic system disorders
WBC (leukocytes)
|
95.8%
23/24 • Number of events 23
|
|
General disorders
weakness
|
29.2%
7/24 • Number of events 7
|
|
General disorders
weight gain
|
8.3%
2/24 • Number of events 2
|
|
General disorders
weight loss
|
25.0%
6/24 • Number of events 6
|
Additional Information
Asad Bashey, MD, PhD, Principal Investigator
Blood and Marrow Transplant Group of Georgia
Phone: 404-255-1930
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60