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Sirolimus, Tacrolimus, and Antithymocyte Globulin in Preventing Graft-Versus-Host Disease in Patients With Hematologic Cancer Who Are Undergoing Donor Stem Cell Transplant

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ClinicalTrials.gov Identifier: NCT00691015
Recruitment Status : Completed
First Posted : June 5, 2008
Results First Posted : June 28, 2017
Last Update Posted : June 28, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Zaid Al-Kadhimi, Barbara Ann Karmanos Cancer Institute

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Supportive Care
Conditions Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Interventions Biological: rituximab
Drug: busulfan
Drug: carmustine
Drug: cyclophosphamide
Drug: cytarabine
Drug: etoposide
Drug: fludarabine phosphate
Drug: melphalan
Radiation: total body irradiation (TBI)
Drug: anti-thymocyte globulin IV
Enrollment 48
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Conditioning Regimen
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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.

Period Title: Overall Study
Started 48
Completed 47
Not Completed 1
Reason Not Completed
Refused further treatment             1
Arm/Group Title All Participants
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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.

Overall Number of Baseline Participants 47
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 47 participants
53
(20 to 70)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 47 participants
Female
17
  36.2%
Male
30
  63.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 47 participants
47
1.Primary Outcome
Title Incidence of Acute Graft-versus-host Disease (GVHD)
Hide Description [Not Specified]
Time Frame Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteria
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[Not Specified]
Arm/Group Title All Participants
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All regimens were analyzed together.
Overall Number of Participants Analyzed 47
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
44.7
(33.4 to 56.6)
2.Primary Outcome
Title Severity of Acute Graft-versus-host Disease (GVHD)
Hide Description [Not Specified]
Time Frame Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteria
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The patients that contracted sever acute graph versus host disease (aGVHD) from those who developed aGVHD
Arm/Group Title All Participants
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All regimens were analyzed together.
Overall Number of Participants Analyzed 21
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: % of participants with severe aGVHD
33.3
(19.2 to 51.3)
3.Primary Outcome
Title Safety, as Defined by Serious Adverse Events and Adverse Events Related to Study Treatment.
Hide Description [Not Specified]
Time Frame Within 6 months after PBSCT
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All participants
Arm/Group Title All Participants
Hide Arm/Group Description:
All regimens were analyzed together.
Overall Number of Participants Analyzed 47
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: % of participants with a reported SAE
93.62
(82.46 to 98.66)
4.Secondary Outcome
Title Incidence of Chronic GVHD.
Hide Description [Not Specified]
Time Frame Within 2 years after PBSCT
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All participants
Arm/Group Title All Participants
Hide Arm/Group Description:
All regimens were analyzed together.
Overall Number of Participants Analyzed 47
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
44.68
(30.17 to 59.88)
5.Secondary Outcome
Title Time to Engraftment (i.e., Absolute Neutrophil Recovery [ANC > 500/mm³] )
Hide Description [Not Specified]
Time Frame post transplant, up to 4 weeks
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All participants
Arm/Group Title All Participants
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All regimens were analyzed together.
Overall Number of Participants Analyzed 47
Median (Full Range)
Unit of Measure: Days
11
(9 to 15)
6.Secondary Outcome
Title Overall Survival.
Hide Description [Not Specified]
Time Frame At 2 years after PBSCT
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[Not Specified]
Arm/Group Title All Participants
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All regimens were analyzed together.
Overall Number of Participants Analyzed 47
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
57.4
(44.9 to 73.5)
7.Secondary Outcome
Title Incidence of Infections, Including Bacterial, Fungal, and Viral Infections (i.e., CMV and EBV Reactivation, Including Post-transplant Lymphoproliferative Disorders)
Hide Description [Not Specified]
Time Frame Within 6 months after PBSCT
Hide Outcome Measure Data
Hide Analysis Population Description
All participants
Arm/Group Title All Participants
Hide Arm/Group Description:
All regimens were analyzed together.
Overall Number of Participants Analyzed 47
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
80.85
(66.74 to 90.85)
8.Secondary Outcome
Title Karnofsky Performance Status Performance Status
Hide Description

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

Time Frame At 90 days after PBSCT
Hide Outcome Measure Data
Hide Analysis Population Description
All participants
Arm/Group Title All Participants
Hide Arm/Group Description:
All regimens were analyzed together.
Overall Number of Participants Analyzed 47
Median (Full Range)
Unit of Measure: units on a scale
80
(60 to 100)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Conditioning Regimen
Hide Arm/Group Description

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.

All-Cause Mortality
Conditioning Regimen
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Conditioning Regimen
Affected / at Risk (%) # Events
Total   44/47 (93.62%)    
Blood and lymphatic system disorders   
Blood/Bone Marrow  1  1/47 (2.13%)  1
Disseminated intravascular coagulation  1  1/47 (2.13%)  1
Febrile neutropenia  1  1/47 (2.13%)  1
Leukocytes  1  12/47 (25.53%)  12
Lymphopenia  1  11/47 (23.40%)  11
Cardiac disorders   
Cardiac ischemia/infarction  1  3/47 (6.38%)  3
Cardiopulmonary arrest  1  2/47 (4.26%)  2
Left Ventricular diastolic dysfunction  1  1/47 (2.13%)  1
Left Ventricular systolic dysfunction  1  1/47 (2.13%)  1
Pain-Cardiovascular-cardiac/heart  1  1/47 (2.13%)  1
Pericardial effusion  1  1/47 (2.13%)  1
Supraventricular and nodal arrhythmia  1  2/47 (4.26%)  2
Tachycardia  1  1/47 (2.13%)  1
Ventricular arrhythmia-ventricular tachycardia  1  1/47 (2.13%)  1
Gastrointestinal disorders   
Ascites  1  4/47 (8.51%)  4
Colitis  1  7/47 (14.89%)  7
Diarrhea  1  6/47 (12.77%)  6
Gastritis  1  2/47 (4.26%)  2
Hemorrhage, GI-Liver  1  1/47 (2.13%)  1
Ileus  1  1/47 (2.13%)  1
Mucositis/stomatis-large bowel  1  2/47 (4.26%)  2
Mucositis/stomatis-Small bowel  1  1/47 (2.13%)  1
Nausea  1  7/47 (14.89%)  7
Pain-Gastrointestinal-Abdominal NOS  1  1/47 (2.13%)  1
Pain-Gastrointestinal-oral cavity  1  4/47 (8.51%)  4
Pain-gastrointestinal-stomach  1  1/47 (2.13%)  1
Vomiting  1  3/47 (6.38%)  3
General disorders   
Fatigue  1  1/47 (2.13%)  1
Fever  1  1/47 (2.13%)  1
Hemorrhage, GI  1  4/47 (8.51%)  4
Rigors/chills  1  2/47 (4.26%)  2
Death-disease progression  1  2/47 (4.26%)  2
Death-disease progression NOS  1  1/47 (2.13%)  1
Death-GVHD  1  1/47 (2.13%)  1
Death SOS  1  1/47 (2.13%)  1
Death-cGVHD  1  3/47 (6.38%)  3
Death-aGVHD/infection  1  1/47 (2.13%)  1
Death-Multi organ failure  1  2/47 (4.26%)  2
Death-Multi organ failure/SOS  1  1/47 (2.13%)  1
Death-pancytopenia possible bleed  1  1/47 (2.13%)  1
Death-Disease progression (from 2nd BMT not associated with this protocol)  1  1/47 (2.13%)  1
Death-aGVHD  1  1/47 (2.13%)  1
Hepatobiliary disorders   
Hepatobiliary/Pancreas - Other (VOD/SOS)  1  3/47 (6.38%)  3
Liver Dysfunction/Failure  1  1/47 (2.13%)  1
Immune system disorders   
Cytokine release syndrome  1  1/47 (2.13%)  1
Infections and infestations   
Infection  1  24/47 (51.06%)  24
Infection BK  1  6/47 (12.77%)  6
Infection CMV  1  6/47 (12.77%)  6
Infection EBV  1  4/47 (8.51%)  4
Infection HSV  1  2/47 (4.26%)  2
Infection VZV in CSF  1  1/47 (2.13%)  1
Infections aspergillus  1  2/47 (4.26%)  2
Infection Pulmonary  1  1/47 (2.13%)  1
infection, with normal ANC  1  11/47 (23.40%)  11
Infection-Pulmonary/Upper Resp.  1  2/47 (4.26%)  2
Death-Multi organ failure/Sepsis  1  2/47 (4.26%)  2
Injury, poisoning and procedural complications   
Fracture  1  1/47 (2.13%)  1
Hemorrhage/bleeding associated with surgery, intra-operative or postoperative  1  1/47 (2.13%)  1
Investigations   
alanine aminotransferase (ALT) increased  1  6/47 (12.77%)  6
alanine aminotransferase (ALT), SGPT  1  2/47 (4.26%)  2
aspartate aminotransferase (AST) increased  1  7/47 (14.89%)  7
aspartate aminotransferase (AST) increased, SGOT  1  2/47 (4.26%)  2
Alkaline Phosphatase increased  1  2/47 (4.26%)  2
Bilirubin increased  1  9/47 (19.15%)  9
Cardiac troponin I increased  1  3/47 (6.38%)  3
Creatinine increased  1  7/47 (14.89%)  7
Hemoglobin  1  11/47 (23.40%)  11
Lipase  1  2/47 (4.26%)  2
Lymphocytes  1  3/47 (6.38%)  3
Neutrophils  1  11/47 (23.40%)  11
Platelets  1  12/47 (25.53%)  12
prolonged intubation  1  3/47 (6.38%)  3
Metabolism and nutrition disorders   
Acidosis  1  4/47 (8.51%)  4
Anorexia  1  6/47 (12.77%)  6
Calcium serum - low  1  6/47 (12.77%)  6
Glucose  1  1/47 (2.13%)  1
Hyperglycemia  1  12/47 (25.53%)  12
Iron Overload  1  6/47 (12.77%)  6
Magnesium, Serum high  1  2/47 (4.26%)  2
Magnesium, Serum low  1  1/47 (2.13%)  1
Potassium, Serum high  1  7/47 (14.89%)  7
Potassium, serum low  1  4/47 (8.51%)  4
Sodium, Serum-low  1  4/47 (8.51%)  4
Musculoskeletal and connective tissue disorders   
Arthritis  1  1/47 (2.13%)  1
Pain-mid/back, hip  1  1/47 (2.13%)  1
Pain-Musculoskeletal-Back  1  1/47 (2.13%)  1
Pain-Musculoskeletal-Bone  1  1/47 (2.13%)  1
pain-chest wall  1  1/47 (2.13%)  1
Nervous system disorders   
CNS cerebrovascular ischemia  1  1/47 (2.13%)  1
Encephalopathy  1  1/47 (2.13%)  1
Other-Right side facial droop  1  1/47 (2.13%)  1
Pain-Neurology-head/headache  1  2/47 (4.26%)  2
Pain-Neurology-headache  1  1/47 (2.13%)  1
Somnolence/depressed level of consciousness  1  4/47 (8.51%)  4
Psychiatric disorders   
Confusion  1  5/47 (10.64%)  5
mood alteration  1  1/47 (2.13%)  1
Renal and urinary disorders   
pain-renal/genitourinary  1  1/47 (2.13%)  1
Renal-other-Acute Renal Failure  1  5/47 (10.64%)  5
Respiratory, thoracic and mediastinal disorders   
Acute Respiratory distress  1  2/47 (4.26%)  2
Dyspnea  1  4/47 (8.51%)  4
Hemorrhage, pulmonary/upper respiratory  1  2/47 (4.26%)  2
Hemorrhage, pulmonary/upper respiratory/lung  1  3/47 (6.38%)  3
Hypoxia  1  11/47 (23.40%)  11
Pain Pulmonary/Respiratroy-throat/pharynx/larynx  1  1/47 (2.13%)  1
Pleural effusion  1  2/47 (4.26%)  2
Pneumonitis/pulmonary infiltrates  1  8/47 (17.02%)  8
Pulmonary Edema  1  2/47 (4.26%)  2
Pulmonary Hypertension  1  2/47 (4.26%)  2
Death-intersititial pneumonia  1  1/47 (2.13%)  1
Skin and subcutaneous tissue disorders   
Dermatology/Skin - palmar erythema  1  1/47 (2.13%)  1
Rash  1  1/47 (2.13%)  1
Rash/Desquamation  1  10/47 (21.28%)  10
Vascular disorders   
Hypertension  1  4/47 (8.51%)  4
Hypotension  1  3/47 (6.38%)  3
Thrombosis/embolism (vascular access-related)  1  2/47 (4.26%)  2
Thrombosis/embolism/thrombus  1  1/47 (2.13%)  1
Thrombosis/embolism (left lower extremity)  1  1/47 (2.13%)  1
Thrombosis/embolism (pulmonary)  1  1/47 (2.13%)  1
Thrombotic microangiopathy  1  4/47 (8.51%)  4
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Conditioning Regimen
Affected / at Risk (%) # Events
Total   0/47 (0.00%)    
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Zaid Al-Kadhimi, M. D.
Organization: Barbara Ann Karmanos Institute
Phone: (404) 778-1900
Responsible Party: Zaid Al-Kadhimi, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT00691015     History of Changes
Other Study ID Numbers: 2007-127
P30CA022453 ( U.S. NIH Grant/Contract )
GENZ-WSU-2007-127
2007-127 ( Other Identifier: Barbara Ann Karmanos Cancer Institute )
First Submitted: June 4, 2008
First Posted: June 5, 2008
Results First Submitted: December 9, 2015
Results First Posted: June 28, 2017
Last Update Posted: June 28, 2017