Trial Outcomes & Findings for Sirolimus, Tacrolimus, and Antithymocyte Globulin in Preventing Graft-Versus-Host Disease in Patients With Hematologic Cancer Who Are Undergoing Donor Stem Cell Transplant (NCT NCT00691015)
NCT ID: NCT00691015
Last Updated: 2017-06-28
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
48 participants
Primary outcome timeframe
Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteria
Results posted on
2017-06-28
Participant Flow
Participant milestones
| Measure |
Conditioning Regimen
Chemotherapy or chemotherapy + total body irradiation
Standard of care (SOC) chemotherapy or ( SOC) chemotherapy + total body irradiation (TBI) of one of the following regimens:
Regimen I: Patients receive fludarabine phosphate IV and busulfan IV.
Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV.
Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV.
Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV.
Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV.
Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI.
|
|---|---|
|
Overall Study
STARTED
|
48
|
|
Overall Study
COMPLETED
|
47
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Conditioning Regimen
Chemotherapy or chemotherapy + total body irradiation
Standard of care (SOC) chemotherapy or ( SOC) chemotherapy + total body irradiation (TBI) of one of the following regimens:
Regimen I: Patients receive fludarabine phosphate IV and busulfan IV.
Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV.
Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV.
Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV.
Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV.
Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI.
|
|---|---|
|
Overall Study
Refused further treatment
|
1
|
Baseline Characteristics
Sirolimus, Tacrolimus, and Antithymocyte Globulin in Preventing Graft-Versus-Host Disease in Patients With Hematologic Cancer Who Are Undergoing Donor Stem Cell Transplant
Baseline characteristics by cohort
| Measure |
All Participants
n=47 Participants
All regimens were analyzed together.
Standard of Care (SOC) Chemotherapy or Standard of Care (SOC) Chemotherapy + total body irradiation
SOC chemotherapy or SOC chemotherapy + total body irradiation (TBI) of one of the following regimens:
Regimen I: Patients receive fludarabine phosphate IV and busulfan IV.
Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV.
Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV.
Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV.
Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV.
Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI.
|
|---|---|
|
Age, Continuous
|
53 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
47 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteriaOutcome measures
| Measure |
All Participants
n=47 Participants
All regimens were analyzed together.
|
|---|---|
|
Incidence of Acute Graft-versus-host Disease (GVHD)
|
44.7 percentage of participants
Interval 33.4 to 56.6
|
PRIMARY outcome
Timeframe: Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteriaPopulation: The patients that contracted sever acute graph versus host disease (aGVHD) from those who developed aGVHD
Outcome measures
| Measure |
All Participants
n=21 Participants
All regimens were analyzed together.
|
|---|---|
|
Severity of Acute Graft-versus-host Disease (GVHD)
|
33.3 % of participants with severe aGVHD
Interval 19.2 to 51.3
|
PRIMARY outcome
Timeframe: Within 6 months after PBSCTPopulation: All participants
Outcome measures
| Measure |
All Participants
n=47 Participants
All regimens were analyzed together.
|
|---|---|
|
Safety, as Defined by Serious Adverse Events and Adverse Events Related to Study Treatment.
|
93.62 % of participants with a reported SAE
Interval 82.46 to 98.66
|
SECONDARY outcome
Timeframe: Within 2 years after PBSCTPopulation: All participants
Outcome measures
| Measure |
All Participants
n=47 Participants
All regimens were analyzed together.
|
|---|---|
|
Incidence of Chronic GVHD.
|
44.68 percentage of participants
Interval 30.17 to 59.88
|
SECONDARY outcome
Timeframe: post transplant, up to 4 weeksPopulation: All participants
Outcome measures
| Measure |
All Participants
n=47 Participants
All regimens were analyzed together.
|
|---|---|
|
Time to Engraftment (i.e., Absolute Neutrophil Recovery [ANC > 500/mm³] )
|
11 Days
Interval 9.0 to 15.0
|
SECONDARY outcome
Timeframe: At 2 years after PBSCTOutcome measures
| Measure |
All Participants
n=47 Participants
All regimens were analyzed together.
|
|---|---|
|
Overall Survival.
|
57.4 percentage of participants
Interval 44.9 to 73.5
|
SECONDARY outcome
Timeframe: Within 6 months after PBSCTPopulation: All participants
Outcome measures
| Measure |
All Participants
n=47 Participants
All regimens were analyzed together.
|
|---|---|
|
Incidence of Infections, Including Bacterial, Fungal, and Viral Infections (i.e., CMV and EBV Reactivation, Including Post-transplant Lymphoproliferative Disorders)
|
80.85 percentage of participants
Interval 66.74 to 90.85
|
SECONDARY outcome
Timeframe: At 90 days after PBSCTPopulation: All participants
100 - Normal; no complaints; no evidence of disease. 90 - Able to carry on normal activity; minor signs or symptoms of disease. 80 - Normal activity with effort; some signs or symptoms of disease. 70 - Cares for self; unable to carry on normal activity or to do active work. 60 - Requires occasional assistance, but is able to care for most of their personal needs. 50 - Requires considerable assistance and frequent medical care. 40 - Disabled; requires special care and assistance. 30 - Severely disabled; hospital admission is indicated although death not imminent. 20 - Very sick; hospital admission necessary; active supportive treatment necessary. 10 - Moribund; fatal processes progressing rapidly. 0 - Dead
Outcome measures
| Measure |
All Participants
n=47 Participants
All regimens were analyzed together.
|
|---|---|
|
Karnofsky Performance Status Performance Status
|
80 units on a scale
Interval 60.0 to 100.0
|
Adverse Events
Conditioning Regimen
Serious events: 44 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Conditioning Regimen
n=47 participants at risk
Chemotherapy or chemotherapy + total body irradiation
Standard of care (SOC) chemotherapy or ( SOC) chemotherapy + total body irradiation (TBI) of one of the following regimens:
Regimen I: Patients receive fludarabine phosphate IV and busulfan IV.
Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV.
Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV.
Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV.
Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV.
Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI.
|
|---|---|
|
Investigations
alanine aminotransferase (ALT) increased
|
12.8%
6/47 • Number of events 6
|
|
Investigations
alanine aminotransferase (ALT), SGPT
|
4.3%
2/47 • Number of events 2
|
|
Investigations
aspartate aminotransferase (AST) increased
|
14.9%
7/47 • Number of events 7
|
|
Investigations
aspartate aminotransferase (AST) increased, SGOT
|
4.3%
2/47 • Number of events 2
|
|
Metabolism and nutrition disorders
Acidosis
|
8.5%
4/47 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory distress
|
4.3%
2/47 • Number of events 2
|
|
Investigations
Alkaline Phosphatase increased
|
4.3%
2/47 • Number of events 2
|
|
Metabolism and nutrition disorders
Anorexia
|
12.8%
6/47 • Number of events 6
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
2.1%
1/47 • Number of events 1
|
|
Gastrointestinal disorders
Ascites
|
8.5%
4/47 • Number of events 4
|
|
Investigations
Bilirubin increased
|
19.1%
9/47 • Number of events 9
|
|
Blood and lymphatic system disorders
Blood/Bone Marrow
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
CNS cerebrovascular ischemia
|
2.1%
1/47 • Number of events 1
|
|
Metabolism and nutrition disorders
Calcium serum - low
|
12.8%
6/47 • Number of events 6
|
|
Cardiac disorders
Cardiac ischemia/infarction
|
6.4%
3/47 • Number of events 3
|
|
Investigations
Cardiac troponin I increased
|
6.4%
3/47 • Number of events 3
|
|
Cardiac disorders
Cardiopulmonary arrest
|
4.3%
2/47 • Number of events 2
|
|
Gastrointestinal disorders
Colitis
|
14.9%
7/47 • Number of events 7
|
|
Psychiatric disorders
Confusion
|
10.6%
5/47 • Number of events 5
|
|
Investigations
Creatinine increased
|
14.9%
7/47 • Number of events 7
|
|
Immune system disorders
Cytokine release syndrome
|
2.1%
1/47 • Number of events 1
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
2.1%
1/47 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin - palmar erythema
|
2.1%
1/47 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhea
|
12.8%
6/47 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
8.5%
4/47 • Number of events 4
|
|
Nervous system disorders
Encephalopathy
|
2.1%
1/47 • Number of events 1
|
|
General disorders
Fatigue
|
2.1%
1/47 • Number of events 1
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
2.1%
1/47 • Number of events 1
|
|
General disorders
Fever
|
2.1%
1/47 • Number of events 1
|
|
Injury, poisoning and procedural complications
Fracture
|
2.1%
1/47 • Number of events 1
|
|
Gastrointestinal disorders
Gastritis
|
4.3%
2/47 • Number of events 2
|
|
Metabolism and nutrition disorders
Glucose
|
2.1%
1/47 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
25.5%
12/47 • Number of events 12
|
|
Investigations
Hemoglobin
|
23.4%
11/47 • Number of events 11
|
|
General disorders
Hemorrhage, GI
|
8.5%
4/47 • Number of events 4
|
|
Gastrointestinal disorders
Hemorrhage, GI-Liver
|
2.1%
1/47 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Hemorrhage, pulmonary/upper respiratory
|
4.3%
2/47 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Hemorrhage, pulmonary/upper respiratory/lung
|
6.4%
3/47 • Number of events 3
|
|
Injury, poisoning and procedural complications
Hemorrhage/bleeding associated with surgery, intra-operative or postoperative
|
2.1%
1/47 • Number of events 1
|
|
Hepatobiliary disorders
Hepatobiliary/Pancreas - Other (VOD/SOS)
|
6.4%
3/47 • Number of events 3
|
|
Vascular disorders
Hypertension
|
8.5%
4/47 • Number of events 4
|
|
Vascular disorders
Hypotension
|
6.4%
3/47 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
23.4%
11/47 • Number of events 11
|
|
Gastrointestinal disorders
Ileus
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Infection
|
51.1%
24/47 • Number of events 24
|
|
Infections and infestations
Infection BK
|
12.8%
6/47 • Number of events 6
|
|
Infections and infestations
Infection CMV
|
12.8%
6/47 • Number of events 6
|
|
Infections and infestations
Infection EBV
|
8.5%
4/47 • Number of events 4
|
|
Infections and infestations
Infection HSV
|
4.3%
2/47 • Number of events 2
|
|
Infections and infestations
Infection VZV in CSF
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Infections aspergillus
|
4.3%
2/47 • Number of events 2
|
|
Infections and infestations
Infection Pulmonary
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
infection, with normal ANC
|
23.4%
11/47 • Number of events 11
|
|
Infections and infestations
Infection-Pulmonary/Upper Resp.
|
4.3%
2/47 • Number of events 2
|
|
Metabolism and nutrition disorders
Iron Overload
|
12.8%
6/47 • Number of events 6
|
|
Cardiac disorders
Left Ventricular diastolic dysfunction
|
2.1%
1/47 • Number of events 1
|
|
Cardiac disorders
Left Ventricular systolic dysfunction
|
2.1%
1/47 • Number of events 1
|
|
Blood and lymphatic system disorders
Leukocytes
|
25.5%
12/47 • Number of events 12
|
|
Investigations
Lipase
|
4.3%
2/47 • Number of events 2
|
|
Hepatobiliary disorders
Liver Dysfunction/Failure
|
2.1%
1/47 • Number of events 1
|
|
Investigations
Lymphocytes
|
6.4%
3/47 • Number of events 3
|
|
Blood and lymphatic system disorders
Lymphopenia
|
23.4%
11/47 • Number of events 11
|
|
Metabolism and nutrition disorders
Magnesium, Serum high
|
4.3%
2/47 • Number of events 2
|
|
Metabolism and nutrition disorders
Magnesium, Serum low
|
2.1%
1/47 • Number of events 1
|
|
Psychiatric disorders
mood alteration
|
2.1%
1/47 • Number of events 1
|
|
Gastrointestinal disorders
Mucositis/stomatis-large bowel
|
4.3%
2/47 • Number of events 2
|
|
Gastrointestinal disorders
Mucositis/stomatis-Small bowel
|
2.1%
1/47 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
14.9%
7/47 • Number of events 7
|
|
Investigations
Neutrophils
|
23.4%
11/47 • Number of events 11
|
|
Nervous system disorders
Other-Right side facial droop
|
2.1%
1/47 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pain Pulmonary/Respiratroy-throat/pharynx/larynx
|
2.1%
1/47 • Number of events 1
|
|
Gastrointestinal disorders
Pain-Gastrointestinal-Abdominal NOS
|
2.1%
1/47 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain-mid/back, hip
|
2.1%
1/47 • Number of events 1
|
|
Cardiac disorders
Pain-Cardiovascular-cardiac/heart
|
2.1%
1/47 • Number of events 1
|
|
Gastrointestinal disorders
Pain-Gastrointestinal-oral cavity
|
8.5%
4/47 • Number of events 4
|
|
Gastrointestinal disorders
Pain-gastrointestinal-stomach
|
2.1%
1/47 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain-Musculoskeletal-Back
|
2.1%
1/47 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain-Musculoskeletal-Bone
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Pain-Neurology-head/headache
|
4.3%
2/47 • Number of events 2
|
|
Nervous system disorders
Pain-Neurology-headache
|
2.1%
1/47 • Number of events 1
|
|
Renal and urinary disorders
pain-renal/genitourinary
|
2.1%
1/47 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
pain-chest wall
|
2.1%
1/47 • Number of events 1
|
|
Cardiac disorders
Pericardial effusion
|
2.1%
1/47 • Number of events 1
|
|
Investigations
Platelets
|
25.5%
12/47 • Number of events 12
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
4.3%
2/47 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis/pulmonary infiltrates
|
17.0%
8/47 • Number of events 8
|
|
Metabolism and nutrition disorders
Potassium, Serum high
|
14.9%
7/47 • Number of events 7
|
|
Metabolism and nutrition disorders
Potassium, serum low
|
8.5%
4/47 • Number of events 4
|
|
Investigations
prolonged intubation
|
6.4%
3/47 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Edema
|
4.3%
2/47 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Hypertension
|
4.3%
2/47 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.1%
1/47 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash/Desquamation
|
21.3%
10/47 • Number of events 10
|
|
Renal and urinary disorders
Renal-other-Acute Renal Failure
|
10.6%
5/47 • Number of events 5
|
|
General disorders
Rigors/chills
|
4.3%
2/47 • Number of events 2
|
|
Metabolism and nutrition disorders
Sodium, Serum-low
|
8.5%
4/47 • Number of events 4
|
|
Nervous system disorders
Somnolence/depressed level of consciousness
|
8.5%
4/47 • Number of events 4
|
|
Cardiac disorders
Supraventricular and nodal arrhythmia
|
4.3%
2/47 • Number of events 2
|
|
Cardiac disorders
Tachycardia
|
2.1%
1/47 • Number of events 1
|
|
Vascular disorders
Thrombosis/embolism (vascular access-related)
|
4.3%
2/47 • Number of events 2
|
|
Vascular disorders
Thrombosis/embolism/thrombus
|
2.1%
1/47 • Number of events 1
|
|
Vascular disorders
Thrombosis/embolism (left lower extremity)
|
2.1%
1/47 • Number of events 1
|
|
Vascular disorders
Thrombosis/embolism (pulmonary)
|
2.1%
1/47 • Number of events 1
|
|
Vascular disorders
Thrombotic microangiopathy
|
8.5%
4/47 • Number of events 4
|
|
Cardiac disorders
Ventricular arrhythmia-ventricular tachycardia
|
2.1%
1/47 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
6.4%
3/47 • Number of events 3
|
|
General disorders
Death-disease progression
|
4.3%
2/47 • Number of events 2
|
|
General disorders
Death-disease progression NOS
|
2.1%
1/47 • Number of events 1
|
|
General disorders
Death-GVHD
|
2.1%
1/47 • Number of events 1
|
|
General disorders
Death SOS
|
2.1%
1/47 • Number of events 1
|
|
General disorders
Death-cGVHD
|
6.4%
3/47 • Number of events 3
|
|
General disorders
Death-aGVHD/infection
|
2.1%
1/47 • Number of events 1
|
|
General disorders
Death-Multi organ failure
|
4.3%
2/47 • Number of events 2
|
|
General disorders
Death-Multi organ failure/SOS
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Death-Multi organ failure/Sepsis
|
4.3%
2/47 • Number of events 2
|
|
General disorders
Death-pancytopenia possible bleed
|
2.1%
1/47 • Number of events 1
|
|
General disorders
Death-Disease progression (from 2nd BMT not associated with this protocol)
|
2.1%
1/47 • Number of events 1
|
|
General disorders
Death-aGVHD
|
2.1%
1/47 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Death-intersititial pneumonia
|
2.1%
1/47 • Number of events 1
|
Other adverse events
Adverse event data not reported
Additional Information
Zaid Al-Kadhimi, M. D.
Barbara Ann Karmanos Institute
Phone: (404) 778-1900
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place