Sirolimus/Tacrolimus Versus Tacrolimus/Methotrexate for Preventing Graft-Versus-Host Disease (GVHD) (BMT CTN 0402)

• Sponsor: Medical College of Wisconsin (Other)
• Overall Status: Completed
• CT.gov ID: NCT00406393
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), Blood and Marrow Transplant Clinical Trials Network (Other), National Cancer Institute (NCI) (NIH)
• Enrollment: 304
• Locations: 24
• Arms: 2
• Duration (Months): 107
• Patients Per Site: 12.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The study is designed as a phase III, randomized, open label, multicenter, prospective, comparative trial of sirolimus and tacrolimus versus tacrolimus and methotrexate as graft-versus-host disease (GVHD) prophylaxis after human leukocyte antigen (HLA)-matched, related, peripheral blood stem cell transplantation in individuals with hematologic cancer. Participants will be stratified by transplant center and will be randomly assigned to the sirolimus/tacrolimus or tacrolimus/methotrexate arms at a 1:1 ratio.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Myelocytic, Acute; Leukemia, Lymphocytic, Acute; Leukemia, Myeloid, Chronic; Myelodysplastic Syndromes	Drug: Tacrolimus; Drug: Methotrexate; Drug: Sirolimus	Phase 3

Detailed Description

BACKGROUND:

Stem cell transplantation is a standard therapy for acute and chronic leukemias and myelodysplastic disorders. A common problem that may occur after a stem cell transplant is a condition known as GVHD. The purpose of this study is to compare two combinations of medications to see which is better at preventing GVHD. The combinations of medications in this study are:

• Sirolimus and tacrolimus

• Methotrexate and tacrolimus

Doctors want to know if one combination is better than the other or if they both have the same result.

DESIGN NARRATIVE:

Participants will receive one of the two conditioning regimens described in the protocol, at the discretion of the transplant physician. The transplant physician must choose among these regimens prior to the participant's assignment to the GVHD prophylaxis treatment. Conditioning regimens will vary by center, but will be the same for all participants at each center. Stem cell donors will donate peripheral blood stem cells according to local institutional practices. Peripheral blood stem cells will not be manipulated or T-depleted prior to administration. Standard post-transplant care will be administered. Participants will be randomly assigned to one of two GVHD prophylaxis regimens and will be followed for the endpoints of interest.

Participants will be followed for 114 days post-randomization for evaluation of the primary endpoint, with additional follow-up for 2 years after transplantation for evaluation of secondary endpoints.

Study Design

• Study Type: Interventional
• Actual Enrollment: 304 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Randomized, Multicenter Trial Comparing Sirolimus/Tacrolimus With Tacrolimus/Methotrexate as Graft-versus-Host Disease (GVHD) Prophylaxis After HLA-Matched, Related Peripheral Blood Stem Cell Transplantation (BMT CTN #0402)
• Study Start Date: Nov 1, 2006
• Actual Primary Completion Date: Oct 1, 2012
• Actual Study Completion Date: Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Tacrolimus/Methotrexate Patients will be given Tacrolimus and Methotrexate for GVHD prophylaxis.	Drug: Tacrolimus; Adults and Children: Tacrolimus will be given at a dose of 0.02 mg/kg every 24 hours as a continuous intravenous infusion beginning on Day -3. An effort will be made to convert the tacrolimus to oral dosing at 2-3 times the total 24-hour intravenous dose, split into 2 doses given every 12 hours as soon as clinically feasible. The target serum level for tacrolimus is 5-10 ng/mL.; Other Names: Prograf® FK506 ; Drug: Methotrexate; Methotrexate will be given at a dose of 15 mg/m2 on Day 1 after transplantation, and at a dose of 10 mg/m2 on Days 3, 6 and 11 after transplantation.; Other Names: MTX
Experimental: Tacrolimus/Sirolimus Patients will be given Tacrolimus and Sirolimus for GVHD prophylaxis.	Drug: Tacrolimus; Adults and Children: Tacrolimus will be given at a dose of 0.02 mg/kg every 24 hours as a continuous intravenous infusion beginning on Day -3. An effort will be made to convert the tacrolimus to oral dosing at 2-3 times the total 24-hour intravenous dose, split into 2 doses given every 12 hours as soon as clinically feasible. The target serum level for tacrolimus is 5-10 ng/mL.; Other Names: Prograf® FK506 ; Drug: Sirolimus; Adults: Sirolimus will be given in a loading dose of 12 mg on Day -3 followed by a daily oral dose of 4 mg per day. Doses may be repeated if the subject vomits within 15 minutes of an oral dose. Children: Children aged < 12.0 years OR weighing < 40.0 kg will be given an oral loading dose of sirolimus of 3 mg/m2 followed by a daily oral dose of 1 mg/m2, rounded to the nearest full milligram. The target serum level for sirolimus is 3-12 ng/mL.; Other Names: Rapamycin Rapamune

Outcome Measures

Primary Outcome Measures

1. Rate of Grades II-IV Acute GVHD-free Survival [Day 114]

   The primary objective is to compare rates of 114-day Grades II-IV acute GVHD-free survival post randomization for HLA-matched, related donor allogeneic peripheral blood stem cell transplantation using two different GVHD prophylaxis regimens. Participants are graded on a scale of 1 to 4 according to their symptoms and organs involved, where 4 represents a worse grade.

Secondary Outcome Measures

1. Incidence of Acute GVHD [Measured at Day 100]

   Cumulative incidence of acute GVHD (grade II-IV) occurring 100 days from transplantation.

2. Time to Neutrophil and Platelet Engraftment [Measured through Day 100]

   Neutrophil engraftment is defined as achieving an Absolute Neutrophil Count (ANC) > 500/mcL for three consecutive measurements on different days. Platelet engraftment is defined as a platelet count > 20,000/mcL for three consecutive measurements over three or more days.

3. Mucositis Severity [Measured at Day 21]

   Mucositis severity will be scored per the modified Oral Mucositis Assessment Scale (OMAS) scoring system on a scale of 0 - 4, where 0 equals normal mucosa and 4 represents severe mucosa.

4. Rate of Veno-occlusive Disease (VOD) [Measured through Day 100]

   VOD will be defined as the occurrence of VOD (based on the Baltimore Criteria for the diagnosis of VOD) in conjunction with other end-organ dysfunction.

5. Thrombotic Microangiopathy (TMA) Infection [Measured through Day 100]

   The occurrence of TMA within the first 100 days after stem cell transplantation will be recorded. The first day of onset will be used for reporting purposes.

6. Reactivation of Cytomegalovirus (CMV) Infection [Measured at Year 2]

7. Treatment-related Mortality [Measured at Day 100 and Year 2]

8. Malignant Disease Relapse [Measured at Year 2]

   Testing for recurrent malignancy in the blood, marrow or other sites will be used to assess relapse after transplantation. For the purpose of this study, relapse is defined by either morphological or cytogenetic evidence of AML, ALL, CML, MDS or CMML consistent with pre-transplant features.

9. Overall Survival [Measured at Year 2]

10. Infections [Measured at Year 2]

11. Time to Discharge After Transplant [Measured at Year 2]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 6/6 HLA-matched sibling, defined by Class I (HLA-A and B) serologic typing (or higher resolution) and Class II (HLA-DRBI) molecular typing, who is willing to donate peripheral blood stem cells, and meets institutional criteria for stem cell donation. The donor must be medically eligible to donate stem cells, according to individual transplant center criteria. Pediatric patients for whom a pediatric sibling donor is not anticipated to be a suitable leukapheresis candidate are not eligible.

• Karnofsky performance status of at least 70% or Lansky performance status of at least 70% for participants less than 16 years old

• For participants less than 18 years old, willing and able to take oral medications, per the treating physician's recommendations

Exclusion Criteria:

• Prior allogeneic or autologous transplant using any hematopoietic stem cell source

• Seropositive for the human immunodeficiency virus (HIV)

• Uncontrolled bacterial, viral, or fungal infection (currently taking medication and progression of clinical symptoms)

• Pregnant (positive serum human chorionic gonadotropin [β-HCG] test) or breastfeeding within 4 weeks of study entry

• Kidney function: serum creatinine outside the normal range for age, or measured creatinine clearance less than 50 mL/min/1.72m^2 within 4 weeks of study entry

• Liver function: most recent direct bilirubin, alanine aminotransferase (ALT), or aspartate aminotransferase (AST) greater than two times the upper limit of normal within 4 weeks of study entry

• Lung disease: in adults, forced vital capacity (FVC) or forced expiratory volume in one second (FEV1) less than 60% of predicted value (corrected for hemoglobin); in children, overt hypoxemia, as measured by an oxygen saturation of less than 92% within 4 weeks of study entry

• Cardiac ejection fraction of less than 45% in adults and children, or less than 26% shortening fraction in children within 4 weeks of study entry

• Cholesterol level greater than 500 mg/dL or triglyceride level greater than 500 mg/dL while being treated, or not on appropriate lipid-lowering therapy within 4 weeks of study entry

• Prior history of allergy to sirolimus

• Requires voriconazole at time of study entry

• Currently receiving another investigational drug unless cleared by the protocol officer or protocol chair

• Participants with a history of cancer, other than resected basal cell carcinoma or treated carcinoma in-situ. Cancer treated with curative intent for more than 5 years previously will be allowed. Cancer treated with curative intent for less than 5 years previously will not be allowed unless approved by the protocol officer or protocol chair.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope National Medical Center	Duarte	California	United States	91010
2	UCSD Medical Center	LaJolla	California	United States	92093
3	Stanford Hospital and Clinics	Stanford	California	United States	94305
4	University of Florida College of Medicine (Shands)	Gainesville	Florida	United States	32610
5	Emory University	Atlanta	Georgia	United States	30322
6	Indiana University Medical Center	Indianapolis	Indiana	United States	46202
7	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242-1009
8	DFCI/Brigham & Women's Hospital	Boston	Massachusetts	United States	02114
9	University of Michigan Medical Center	Ann Arbor	Michigan	United States	48109-0914
10	University of Minnesota	Minneapolis	Minnesota	United States	55455
11	Mayo Clinic	Rochester	Minnesota	United States	55905
12	Washington University/Barnes Jewish Hospital	St. Louis	Missouri	United States	63110
13	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
14	Duke University Medical Center	Durham	North Carolina	United States	27705
15	University Hospitals of Cleveland/Case Western	Cleveland	Ohio	United States	44106-5061
16	Ohio State, Arthur G. James Cancer Hospital	Columbus	Ohio	United States	43210
17	University of Oklahoma Medical Center	Oklahoma City	Oklahoma	United States	73104
18	Oregon Health & Science University	Portland	Oregon	United States	97239
19	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania	United States	19104
20	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15232
21	Texas Transplant Institute	San Antonio	Texas	United States	78229
22	Virginia Commonwealth University/MCV Hospital	Richmond	Virginia	United States	23298
23	University of Wisconsin Hospital & Clinics	Madison	Wisconsin	United States	53792-5156
24	Hopital Saint-Louis	Paris		France	CEDEX 10

Sponsors and Collaborators

• Medical College of Wisconsin
• National Heart, Lung, and Blood Institute (NHLBI)
• Blood and Marrow Transplant Clinical Trials Network
• National Cancer Institute (NCI)

Investigators

• Study Director: Mary Horowitz, MD, Center for International Blood and Marrow Transplant Research

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Blood and Marrow Transplant Clinical Trials Network

Publications

None provided.

• Responsible Party: Medical College of Wisconsin
• ClinicalTrials.gov Identifier: NCT00406393
• Other Study ID Numbers: BMTCTN0402; U01HL069294; BMT CTN 0402; U01HL069294-05
• First Posted: Dec 4, 2006
• Last Update Posted: Mar 7, 2016
• Last Verified: Feb 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Medical College of Wisconsin: Acute Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Chronic Myelogenous Leukemia
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Graft vs Host Disease; Sirolimus; Methotrexate; Tacrolimus

Study Results

Participant Flow

Recruitment Details	Participants were enrolled from 2006 to 2011 from 24 different transplant centers.

Arm/Group Title	Tacrolimus/Sirolimus	Tacrolimus/Methotrexate
Arm/Group Description	Patients will be given Tacrolimus and Sirolimus for GVHD prophylaxis.	Patients will be given Tacrolimus and Methotrexate for GVHD prophylaxis.
Period Title: Overall Study
STARTED	151	153
COMPLETED	149	152
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Tacrolimus/Sirolimus	Tacrolimus/Methotrexate	Total
Arm/Group Description	Patients will be given Tacrolimus and Sirolimus for GVHD prophylaxis.	Patients will be given Tacrolimus and Methotrexate for GVHD prophylaxis.	Total of all reporting groups
Overall Participants	151	153	304
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	45	43	44
Sex: Female, Male (Count of Participants)
Female	74 49%	68 44.4%	142 46.7%
Male	77 51%	85 55.6%	162 53.3%
Primary Disease (participants) [Number]
Acute Myelogenous Leukemia (AML)	71 47%	63 41.2%	134 44.1%
Acute Lymphoblastic Leukemia (ALL)	51 33.8%	68 44.4%	119 39.1%
Chronic Myelogenous Leukemia (CML)	9 6%	14 9.2%	23 7.6%
Myelodysplastic Syndrome (MDS)	19 12.6%	7 4.6%	26 8.6%
Acute Biphenotypic Leukemia (ABL)	1 0.7%	1 0.7%	2 0.7%
Disease Status at Transplantation (participants) [Number]
AML 1st Complete Remission	60 39.7%	56 36.6%	116 38.2%
AML 2nd Complete Remission	11 7.3%	7 4.6%	18 5.9%
ALL 1st Complete Remission	41 27.2%	55 35.9%	96 31.6%
ALL 2nd Complete Remission	10 6.6%	13 8.5%	23 7.6%
CML 1st Complete Remission	7 4.6%	10 6.5%	17 5.6%
CML 2nd Complete Remission	2 1.3%	4 2.6%	6 2%
ABL 1st Complete Remission	1 0.7%	1 0.7%	2 0.7%
MDS	19 12.6%	7 4.6%	26 8.6%
Karnofsky Score (participants) [Number]
Scores 90 - 100	101 66.9%	116 75.8%	217 71.4%
Scores < 90	50 33.1%	37 24.2%	87 28.6%
Recipient-Donor Cytomegalovirus Status (participants) [Number]
+/+	59 39.1%	47 30.7%	106 34.9%
+/-	14 9.3%	24 15.7%	38 12.5%
-/+	30 19.9%	44 28.8%	74 24.3%
-/-	38 25.2%	30 19.6%	68 22.4%
Missing	10 6.6%	8 5.2%	18 5.9%
Conditioning Regimen (participants) [Number]
Cyclophosphamide/Total Body Irradiation	124 82.1%	122 79.7%	246 80.9%
Etoposide/Total Body Irradiation	27 17.9%	31 20.3%	58 19.1%

Outcome Measures

1. Primary Outcome

Title	Rate of Grades II-IV Acute GVHD-free Survival
Description	The primary objective is to compare rates of 114-day Grades II-IV acute GVHD-free survival post randomization for HLA-matched, related donor allogeneic peripheral blood stem cell transplantation using two different GVHD prophylaxis regimens. Participants are graded on a scale of 1 to 4 according to their symptoms and organs involved, where 4 represents a worse grade.
Time Frame	Day 114

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus/Sirolimus	Tacrolimus/Methotrexate
Arm/Group Description	Patients will be given Tacrolimus and Sirolimus for GVHD prophylaxis.	Patients will be given Tacrolimus and Methotrexate for GVHD prophylaxis.
Measure Participants	149	152
Number (95% Confidence Interval) [percentage of participants]	67 44.4%	62 40.5%

2. Secondary Outcome

Title	Incidence of Acute GVHD
Description	Cumulative incidence of acute GVHD (grade II-IV) occurring 100 days from transplantation.
Time Frame	Measured at Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus/Sirolimus	Tacrolimus/Methotrexate
Arm/Group Description	Patients will be given Tacrolimus and Sirolimus for GVHD prophylaxis.	Patients will be given Tacrolimus and Methotrexate for GVHD prophylaxis.
Measure Participants	149	152
Number (95% Confidence Interval) [percentage of participants]	26 17.2%	34 22.2%

3. Secondary Outcome

Title	Time to Neutrophil and Platelet Engraftment
Description	Neutrophil engraftment is defined as achieving an Absolute Neutrophil Count (ANC) > 500/mcL for three consecutive measurements on different days. Platelet engraftment is defined as a platelet count > 20,000/mcL for three consecutive measurements over three or more days.
Time Frame	Measured through Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus/Sirolimus	Tacrolimus/Methotrexate
Arm/Group Description	Patients will be given Tacrolimus and Sirolimus for GVHD prophylaxis.	Patients will be given Tacrolimus and Methotrexate for GVHD prophylaxis.
Measure Participants	149	152
Neutrophil Engraftment	14	16
Platelet Engraftment	16	19

4. Secondary Outcome

Title	Mucositis Severity
Description	Mucositis severity will be scored per the modified Oral Mucositis Assessment Scale (OMAS) scoring system on a scale of 0 - 4, where 0 equals normal mucosa and 4 represents severe mucosa.
Time Frame	Measured at Day 21

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus/Sirolimus	Tacrolimus/Methotrexate
Arm/Group Description	Patients will be given Tacrolimus and Sirolimus for GVHD prophylaxis.	Patients will be given Tacrolimus and Methotrexate for GVHD prophylaxis.
Measure Participants	149	152
Mean (Standard Deviation) [units on a scale]	0.31 (0.28)	0.47 (0.40)

5. Secondary Outcome

Title	Rate of Veno-occlusive Disease (VOD)
Description	VOD will be defined as the occurrence of VOD (based on the Baltimore Criteria for the diagnosis of VOD) in conjunction with other end-organ dysfunction.
Time Frame	Measured through Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus/Sirolimus	Tacrolimus/Methotrexate
Arm/Group Description	Patients will be given Tacrolimus and Sirolimus for GVHD prophylaxis.	Patients will be given Tacrolimus and Methotrexate for GVHD prophylaxis.
Measure Participants	149	152
Number (95% Confidence Interval) [percentage of participants]	11 7.3%	5 3.3%

6. Secondary Outcome

Title	Thrombotic Microangiopathy (TMA) Infection
Description	The occurrence of TMA within the first 100 days after stem cell transplantation will be recorded. The first day of onset will be used for reporting purposes.
Time Frame	Measured through Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus/Sirolimus	Tacrolimus/Methotrexate
Arm/Group Description	Patients will be given Tacrolimus and Sirolimus for GVHD prophylaxis.	Patients will be given Tacrolimus and Methotrexate for GVHD prophylaxis.
Measure Participants	149	152
Number (95% Confidence Interval) [percentage of participants]	5 3.3%	1 0.7%

7. Secondary Outcome

Title	Reactivation of Cytomegalovirus (CMV) Infection
Time Frame	Measured at Year 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus/Sirolimus	Tacrolimus/Methotrexate
Arm/Group Description	Patients will be given Tacrolimus and Sirolimus for GVHD prophylaxis.	Patients will be given Tacrolimus and Methotrexate for GVHD prophylaxis.
Measure Participants	149	152
Number (95% Confidence Interval) [percentage of participants]	13 8.6%	15 9.8%

8. Secondary Outcome

Title	Treatment-related Mortality
Time Frame	Measured at Day 100 and Year 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus/Sirolimus	Tacrolimus/Methotrexate
Arm/Group Description	Patients will be given Tacrolimus and Sirolimus for GVHD prophylaxis.	Patients will be given Tacrolimus and Methotrexate for GVHD prophylaxis.
Measure Participants	149	152
Day 100	7 4.6%	7 4.6%
Year 2	20 13.2%	16 10.5%

9. Secondary Outcome

Title	Malignant Disease Relapse
Description	Testing for recurrent malignancy in the blood, marrow or other sites will be used to assess relapse after transplantation. For the purpose of this study, relapse is defined by either morphological or cytogenetic evidence of AML, ALL, CML, MDS or CMML consistent with pre-transplant features.
Time Frame	Measured at Year 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus/Sirolimus	Tacrolimus/Methotrexate
Arm/Group Description	Patients will be given Tacrolimus and Sirolimus for GVHD prophylaxis.	Patients will be given Tacrolimus and Methotrexate for GVHD prophylaxis.
Measure Participants	149	152
Number (95% Confidence Interval) [percentage of participants]	28 18.5%	29 19%

10. Secondary Outcome

Title	Overall Survival
Time Frame	Measured at Year 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus/Sirolimus	Tacrolimus/Methotrexate
Arm/Group Description	Patients will be given Tacrolimus and Sirolimus for GVHD prophylaxis.	Patients will be given Tacrolimus and Methotrexate for GVHD prophylaxis.
Measure Participants	149	152
Number (95% Confidence Interval) [percentage of participants]	59 39.1%	63 41.2%

11. Secondary Outcome

Title	Infections
Time Frame	Measured at Year 2

Outcome Measure Data

Analysis Population Description

Insufficient data to report on this outcome measure

Arm/Group Title	Tacrolimus/Sirolimus	Tacrolimus/Methotrexate
Arm/Group Description	Patients will be given Tacrolimus and Sirolimus for GVHD prophylaxis.	Patients will be given Tacrolimus and Methotrexate for GVHD prophylaxis.
Measure Participants	0	0

12. Secondary Outcome

Title	Time to Discharge After Transplant
Time Frame	Measured at Year 2

Outcome Measure Data

Analysis Population Description

Insufficient data to report on this outcome measure

Arm/Group Title	Tacrolimus/Sirolimus	Tacrolimus/Methotrexate
Arm/Group Description	Patients will be given Tacrolimus and Sirolimus for GVHD prophylaxis.	Patients will be given Tacrolimus and Methotrexate for GVHD prophylaxis.
Measure Participants	0	0

Adverse Events

Time Frame	2-years post transplant
Adverse Event Reporting Description	Serious adverse events are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event.
Arm/Group Title	Tacrolimus/Sirolimus		Tacrolimus/Methotrexate
Arm/Group Description	Patients will be given Tacrolimus and Sirolimus for GVHD prophylaxis.		Patients will be given Tacrolimus and Methotrexate for GVHD prophylaxis.
All Cause Mortality
	Tacrolimus/Sirolimus		Tacrolimus/Methotrexate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Tacrolimus/Sirolimus		Tacrolimus/Methotrexate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/149 (6%)		12/152 (7.9%)
Cardiac disorders
Pericardial effusion	0/149 (0%)		1/152 (0.7%)	1
Supraventricular tachycardia	0/149 (0%)		1/152 (0.7%)	1
Eye disorders
Retinal tear	1/149 (0.7%)	1	0/152 (0%)	1
Glaucoma	0/149 (0%)		1/152 (0.7%)	1
General disorders
Death	1/149 (0.7%)	1	0/152 (0%)	1
Chest pain	1/149 (0.7%)	1	0/152 (0%)	1
Hepatobiliary disorders
Cholecystitis	0/149 (0%)		1/152 (0.7%)	1
Infections and infestations
Staphylococcal infection	1/149 (0.7%)	1	0/152 (0%)	1
Septic shock	0/149 (0%)		1/152 (0.7%)	1
Injury, poisoning and procedural complications
Subdural haematoma	0/149 (0%)		1/152 (0.7%)	1
Musculoskeletal and connective tissue disorders
Osteonecrosis	1/149 (0.7%)	1	0/152 (0%)	1
Myositis	0/149 (0%)		1/152 (0.7%)	1
Nervous system disorders
Aphasia	1/149 (0.7%)	1	0/152 (0%)	1
Cerebrovascular accident	0/149 (0%)		1/152 (0.7%)	1
VIIth nerve paralysis	0/149 (0%)		1/152 (0.7%)	1
Neuropathy peripheral	0/149 (0%)		1/152 (0.7%)	1
Psychiatric disorders
Mental status changes	1/149 (0.7%)	1	0/152 (0%)	1
Respiratory, thoracic and mediastinal disorders
Pneumothorax	0/149 (0%)		1/152 (0.7%)	1
Pneumonitis	0/149 (0%)		1/152 (0.7%)	1
Surgical and medical procedures
Thoracotomy	1/149 (0.7%)	1	0/152 (0%)	1
Vascular disorders
Embolism	1/149 (0.7%)	1	0/152 (0%)	1
Other (Not Including Serious) Adverse Events
	Tacrolimus/Sirolimus		Tacrolimus/Methotrexate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/149 (0%)		0/152 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.