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Trial record 35 of 36 for:    "Viral Infectious Disease" | "Everolimus"

Tacrolimus and Mycophenolate Mofetil With or Without Sirolimus in Preventing Acute Graft-Versus-Host Disease in Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00105001
Recruitment Status : Completed
First Posted : March 4, 2005
Results First Posted : September 15, 2015
Last Update Posted : March 8, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Brenda Sandmaier, Fred Hutchinson Cancer Research Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
Previously Treated Myelodysplastic Syndrome
Refractory Chronic Lymphocytic Leukemia
Refractory Plasma Cell Myeloma
Waldenstrom Macroglobulinemia
Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Adult Acute Lymphoblastic Leukemia in Remission
Adult Acute Myeloid Leukemia in Remission
Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL
Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11
Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1
Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative
Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Childhood Acute Lymphoblastic Leukemia in Remission
Childhood Acute Myeloid Leukemia in Remission
Childhood Burkitt Lymphoma
Childhood Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Childhood Diffuse Large Cell Lymphoma
Childhood Immunoblastic Lymphoma
Childhood Myelodysplastic Syndrome
Stage II Contiguous Adult Burkitt Lymphoma
Stage II Contiguous Adult Diffuse Large Cell Lymphoma
Stage II Contiguous Adult Diffuse Mixed Cell Lymphoma
Stage II Contiguous Adult Diffuse Small Cleaved Cell Lymphoma
Stage II Adult Contiguous Immunoblastic Lymphoma
Stage II Contiguous Adult Lymphoblastic Lymphoma
Stage II Grade 1 Contiguous Follicular Lymphoma
Stage II Grade 2 Contiguous Follicular Lymphoma
Stage II Grade 3 Contiguous Follicular Lymphoma
Stage II Contiguous Mantle Cell Lymphoma
Stage II Non-Contiguous Adult Burkitt Lymphoma
Stage II Non-Contiguous Adult Diffuse Large Cell Lymphoma
Stage II Non-Contiguous Adult Diffuse Mixed Cell Lymphoma
Stage II Non-Contiguous Adult Diffuse Small Cleaved Cell Lymphoma
Stage II Adult Non-Contiguous Immunoblastic Lymphoma
Stage II Non-Contiguous Adult Lymphoblastic Lymphoma
Stage II Grade 1 Non-Contiguous Follicular Lymphoma
Stage II Grade 2 Non-Contiguous Follicular Lymphoma
Stage II Grade 3 Non-Contiguous Follicular Lymphoma
Stage II Non-Contiguous Mantle Cell Lymphoma
Stage II Small Lymphocytic Lymphoma
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Acute Myeloid Leukemia
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Recurrent Childhood Anaplastic Large Cell Lymphoma
Recurrent Childhood Large Cell Lymphoma
Recurrent Childhood Lymphoblastic Lymphoma
Recurrent Childhood Burkitt Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Small Lymphocytic Lymphoma
Recurrent Childhood Hodgkin Lymphoma
Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Secondary Myelodysplastic Syndrome
Stage I Adult Burkitt Lymphoma
Stage I Adult Diffuse Large Cell Lymphoma
Stage I Adult Diffuse Mixed Cell Lymphoma
Stage I Adult Immunoblastic Lymphoma
Stage I Adult Lymphoblastic Lymphoma
Stage I Childhood Anaplastic Large Cell Lymphoma
Stage I Childhood Large Cell Lymphoma
Stage I Childhood Lymphoblastic Lymphoma
Stage I Childhood Burkitt Lymphoma
Stage I Grade 1 Follicular Lymphoma
Stage I Grade 2 Follicular Lymphoma
Stage I Grade 3 Follicular Lymphoma
Stage I Mantle Cell Lymphoma
Stage I Marginal Zone Lymphoma
Stage I Small Lymphocytic Lymphoma
Stage II Childhood Anaplastic Large Cell Lymphoma
Stage II Childhood Lymphoblastic Lymphoma
Stage II Childhood Burkitt Lymphoma
Stage III Adult Burkitt Lymphoma
Stage III Adult Diffuse Large Cell Lymphoma
Stage III Adult Diffuse Mixed Cell Lymphoma
Stage III Adult Diffuse Small Cleaved Cell Lymphoma
Stage III Adult Immunoblastic Lymphoma
Stage III Adult Lymphoblastic Lymphoma
Stage III Childhood Anaplastic Large Cell Lymphoma
Stage III Childhood Large Cell Lymphoma
Stage III Childhood Lymphoblastic Lymphoma
Stage III Childhood Burkitt Lymphoma
Stage III Grade 1 Follicular Lymphoma
Stage III Grade 2 Follicular Lymphoma
Stage III Grade 3 Follicular Lymphoma
Stage III Mantle Cell Lymphoma
Stage III Marginal Zone Lymphoma
Stage III Small Lymphocytic Lymphoma
Stage IV Adult Burkitt Lymphoma
Stage IV Adult Diffuse Large Cell Lymphoma
Stage IV Adult Diffuse Mixed Cell Lymphoma
Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
Stage IV Adult Immunoblastic Lymphoma
Stage IV Adult Lymphoblastic Lymphoma
Stage IV Childhood Anaplastic Large Cell Lymphoma
Stage IV Childhood Large Cell Lymphoma
Stage IV Childhood Lymphoblastic Lymphoma
Stage IV Childhood Burkitt Lymphoma
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Stage IV Mantle Cell Lymphoma
Stage IV Marginal Zone Lymphoma
Stage IV Small Lymphocytic Lymphoma
Interventions Drug: Fludarabine Phosphate
Radiation: Total-Body Irradiation
Procedure: Peripheral Blood Stem Cell Transplantation
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Drug: Tacrolimus
Drug: Mycophenolate Mofetil
Drug: Sirolimus
Enrollment 210
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm I (MMF and Tacrolimus) Arm II (MMF and Tacrolimus Alternate Schedule) Arm III (MMF, Tacrolimus, and Sirolimus)
Hide Arm/Group Description

Patients receive tacrolimus IV or PO every 12 hours on days -3 to 180 with taper beginning on day 100 in the absence of GVHD. Patients also receive Mycophenolate Mofetil [MMF] PO every 8 hours on days 0-29 and then every 12 hours on days 30-96 with taper beginning on day 40 in the absence of GVHD.

Fludarabine Phosphate: Given IV

Total-Body Irradiation: Undergo total-body irradiation

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Tacrolimus: Given IV or PO

Mycophenolate Mofetil: Given PO

Patients receive tacrolimus IV or PO every 12 hours on days -3 to 150 with taper beginning on day 100 in the absence of GVHD. Patients also receive Mycophenolate Mofetil [MMF] PO every 8 hours on days 0-29 and then every 12 hours on days 30-180 with taper beginning on day 150 in the absence of GVHD.

Fludarabine Phosphate: Given IV

Total-Body Irradiation: Undergo total-body irradiation

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Tacrolimus: Given IV or PO

Mycophenolate Mofetil: Given PO

Patients receive tacrolimus and Mycophenolate Mofetil [MMF] as in arm II. Patients also receive sirolimus PO once daily on days -3 to 80.

Fludarabine Phosphate: Given IV

Total-Body Irradiation: Undergo total-body irradiation

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Tacrolimus: Given IV or PO

Mycophenolate Mofetil: Given PO

Sirolimus: Given PO

Period Title: Overall Study
Started 70 71 69
Completed 70 71 69
Not Completed 0 0 0
Arm/Group Title Arm I (MMF and Tacrolimus) Arm II (MMF and Tacrolimus Alternate Schedule) Arm III (MMF, Tacrolimus, and Sirolimus) Total
Hide Arm/Group Description

Patients receive tacrolimus IV or PO every 12 hours on days -3 to 180 with taper beginning on day 100 in the absence of GVHD. Patients also receive MMF PO every 8 hours on days 0-29 and then every 12 hours on days 30-96 with taper beginning on day 40 in the absence of GVHD.

Fludarabine Phosphate: Given IV

Total-Body Irradiation: Undergo total-body irradiation

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Tacrolimus: Given IV or PO

Mycophenolate Mofetil: Given PO

Patients receive tacrolimus IV or PO every 12 hours on days -3 to 150 with taper beginning on day 100 in the absence of GVHD. Patients also receive MMF PO every 8 hours on days 0-29 and then every 12 hours on days 30-180 with taper beginning on day 150 in the absence of GVHD.

Fludarabine Phosphate: Given IV

Total-Body Irradiation: Undergo total-body irradiation

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Tacrolimus: Given IV or PO

Mycophenolate Mofetil: Given PO

Patients receive tacrolimus and MMF as in arm II. Patients also receive sirolimus PO once daily on days -3 to 80.

Fludarabine Phosphate: Given IV

Total-Body Irradiation: Undergo total-body irradiation

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Tacrolimus: Given IV or PO

Mycophenolate Mofetil: Given PO

Sirolimus: Given PO

Total of all reporting groups
Overall Number of Baseline Participants 70 71 69 210
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 70 participants 71 participants 69 participants 210 participants
<=18 years
0
   0.0%
1
   1.4%
1
   1.4%
2
   1.0%
Between 18 and 65 years
57
  81.4%
50
  70.4%
49
  71.0%
156
  74.3%
>=65 years
13
  18.6%
20
  28.2%
19
  27.5%
52
  24.8%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 70 participants 71 participants 69 participants 210 participants
60
(26 to 74)
60
(13 to 72)
60
(15 to 75)
60
(13 to 75)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 70 participants 71 participants 69 participants 210 participants
Female
29
  41.4%
30
  42.3%
23
  33.3%
82
  39.0%
Male
41
  58.6%
41
  57.7%
46
  66.7%
128
  61.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 70 participants 71 participants 69 participants 210 participants
United States 59 59 58 176
Denmark 5 5 5 15
Germany 6 7 6 19
1.Primary Outcome
Title Incidence of Grades II-IV Acute GVHD
Hide Description

Percentage patients with grades II-IV GHVD, estimated by cumulative incidence methods.

Cumulative incidence methods are the standard way to estimate incidence of an endpoint in the presence of competing risks and censoring (ref)” Here is the reference. Gooley TA, Leisenring W, Crowley J, Storer BE: Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Statistics in Medicine 18:695-706, 1999. PMID 10204198

Time Frame 150 days after transplant
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I (MMF and Tacrolimus) Arm II (MMF and Tacrolimus Alternate Schedule) Arm III (MMF, Tacrolimus, and Sirolimus)
Hide Arm/Group Description:

Patients receive tacrolimus IV or PO every 12 hours on days -3 to 180 with taper beginning on day 100 in the absence of GVHD. Patients also receive MMF PO every 8 hours on days 0-29 and then every 12 hours on days 30-96 with taper beginning on day 40 in the absence of GVHD.

Fludarabine Phosphate: Given IV

Total-Body Irradiation: Undergo total-body irradiation

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Tacrolimus: Given IV or PO

Mycophenolate Mofetil: Given PO

Patients receive tacrolimus IV or PO every 12 hours on days -3 to 150 with taper beginning on day 100 in the absence of GVHD. Patients also receive MMF PO every 8 hours on days 0-29 and then every 12 hours on days 30-180 with taper beginning on day 150 in the absence of GVHD.

Fludarabine Phosphate: Given IV

Total-Body Irradiation: Undergo total-body irradiation

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Tacrolimus: Given IV or PO

Mycophenolate Mofetil: Given PO

Patients receive tacrolimus and MMF as in arm II. Patients also receive sirolimus PO once daily on days -3 to 80.

Fludarabine Phosphate: Given IV

Total-Body Irradiation: Undergo total-body irradiation

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Tacrolimus: Given IV or PO

Mycophenolate Mofetil: Given PO

Sirolimus: Given PO

Overall Number of Participants Analyzed 70 71 69
Measure Type: Number
Unit of Measure: percentage of participants
63 49 46
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I (MMF and Tacrolimus), Arm II (MMF and Tacrolimus Alternate Schedule), Arm III (MMF, Tacrolimus, and Sirolimus)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.09
Comments Overall test of homogeneity among arms, reflecting events over the entire period of follow-up
Method Regression, Cox
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm I (MMF and Tacrolimus), Arm II (MMF and Tacrolimus Alternate Schedule)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.10
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.4 to 1.1
Estimation Comments HR for Arm II relative to Arm I, reflecting events over the entire period of follow-u[
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Arm I (MMF and Tacrolimus), Arm III (MMF, Tacrolimus, and Sirolimus)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
0.6 to 1.0
Estimation Comments HR for Arm III relative to Arm I, reflecting events over the entire period of follow-up
2.Secondary Outcome
Title Incidence of Non-relapse Mortality
Hide Description

Percentage of NRM as estimated by cumulative incidence methods with competing risks.

Cumulative incidence methods are the standard way to estimate incidence of an endpoint in the presence of competing risks and censoring (ref)” Here is the reference. Gooley TA, Leisenring W, Crowley J, Storer BE: Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Statistics in Medicine 18:695-706, 1999. PMID 10204198

Time Frame 200 days after transplant
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I (MMF and Tacrolimus) Arm II (MMF and Tacrolimus Alternate Schedule) Arm III (MMF, Tacrolimus, and Sirolimus)
Hide Arm/Group Description:

Patients receive tacrolimus IV or PO every 12 hours on days -3 to 180 with taper beginning on day 100 in the absence of GVHD. Patients also receive MMF PO every 8 hours on days 0-29 and then every 12 hours on days 30-96 with taper beginning on day 40 in the absence of GVHD.

Fludarabine Phosphate: Given IV

Total-Body Irradiation: Undergo total-body irradiation

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Tacrolimus: Given IV or PO

Mycophenolate Mofetil: Given PO

Patients receive tacrolimus IV or PO every 12 hours on days -3 to 150 with taper beginning on day 100 in the absence of GVHD. Patients also receive MMF PO every 8 hours on days 0-29 and then every 12 hours on days 30-180 with taper beginning on day 150 in the absence of GVHD.

Fludarabine Phosphate: Given IV

Total-Body Irradiation: Undergo total-body irradiation

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Tacrolimus: Given IV or PO

Mycophenolate Mofetil: Given PO

Patients receive tacrolimus and MMF as in arm II. Patients also receive sirolimus PO once daily on days -3 to 80.

Fludarabine Phosphate: Given IV

Total-Body Irradiation: Undergo total-body irradiation

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Tacrolimus: Given IV or PO

Mycophenolate Mofetil: Given PO

Sirolimus: Given PO

Overall Number of Participants Analyzed 70 71 69
Measure Type: Number
Unit of Measure: percentage of participants
4 7 3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I (MMF and Tacrolimus), Arm II (MMF and Tacrolimus Alternate Schedule), Arm III (MMF, Tacrolimus, and Sirolimus)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.55
Comments Overall test of homogeneity among arms, reflecting events over the entire period of follow-up
Method Regression, Cox
Comments [Not Specified]
3.Secondary Outcome
Title Incidence of High-dose Corticosteroid Utilization.
Hide Description

Percentage of patients utilizing high-dose corticosteroid (as a surrogate marker for reduction of acute GVHD), estimated by cumulative incidence methods.

Cumulative incidence methods are the standard way to estimate incidence of an endpoint in the presence of competing risks and censoring (ref)” Here is the reference. Gooley TA, Leisenring W, Crowley J, Storer BE: Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Statistics in Medicine 18:695-706, 1999. PMID 10204198

Time Frame 150 days after transplant
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I (MMF and Tacrolimus) Arm II (MMF and Tacrolimus Alternate Schedule) Arm III (MMF, Tacrolimus, and Sirolimus)
Hide Arm/Group Description:

Patients receive tacrolimus IV or PO every 12 hours on days -3 to 180 with taper beginning on day 100 in the absence of GVHD. Patients also receive MMF PO every 8 hours on days 0-29 and then every 12 hours on days 30-96 with taper beginning on day 40 in the absence of GVHD.

Fludarabine Phosphate: Given IV

Total-Body Irradiation: Undergo total-body irradiation

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Tacrolimus: Given IV or PO

Mycophenolate Mofetil: Given PO

Patients receive tacrolimus IV or PO every 12 hours on days -3 to 150 with taper beginning on day 100 in the absence of GVHD. Patients also receive MMF PO every 8 hours on days 0-29 and then every 12 hours on days 30-180 with taper beginning on day 150 in the absence of GVHD.

Fludarabine Phosphate: Given IV

Total-Body Irradiation: Undergo total-body irradiation

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Tacrolimus: Given IV or PO

Mycophenolate Mofetil: Given PO

Patients receive tacrolimus and MMF as in arm II. Patients also receive sirolimus PO once daily on days -3 to 80.

Fludarabine Phosphate: Given IV

Total-Body Irradiation: Undergo total-body irradiation

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Tacrolimus: Given IV or PO

Mycophenolate Mofetil: Given PO

Sirolimus: Given PO

Overall Number of Participants Analyzed 70 71 69
Measure Type: Number
Unit of Measure: percentage of participants
56 49 32
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I (MMF and Tacrolimus), Arm II (MMF and Tacrolimus Alternate Schedule), Arm III (MMF, Tacrolimus, and Sirolimus)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments Overall test of homogeneity among arms, reflecting events over the entire period of follow-up
Method Regression, Cox
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm I (MMF and Tacrolimus), Arm II (MMF and Tacrolimus Alternate Schedule)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.51
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.5 to 1.4
Estimation Comments HR for Arm II relative to Arm I, reflecting events over the entire period of follow-up
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Arm I (MMF and Tacrolimus), Arm III (MMF, Tacrolimus, and Sirolimus)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
0.3 to 0.8
Estimation Comments HR for Arm III relative to Arm I, reflecting events over the entire period of follow-up
4.Secondary Outcome
Title Overall Survival
Hide Description

Percentage of patients surviving, estimated by cumulative incidence methods

Cumulative incidence methods are the standard way to estimate incidence of an endpoint in the presence of competing risks and censoring (ref)” Here is the reference. Gooley TA, Leisenring W, Crowley J, Storer BE: Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Statistics in Medicine 18:695-706, 1999. PMID 10204198

Time Frame At 6 months and then every year thereafter, up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I (MMF and Tacrolimus) Arm II (MMF and Tacrolimus Alternate Schedule) Arm III (MMF, Tacrolimus, and Sirolimus)
Hide Arm/Group Description:

Patients receive tacrolimus IV or PO every 12 hours on days -3 to 180 with taper beginning on day 100 in the absence of GVHD. Patients also receive MMF PO every 8 hours on days 0-29 and then every 12 hours on days 30-96 with taper beginning on day 40 in the absence of GVHD.

Fludarabine Phosphate: Given IV

Total-Body Irradiation: Undergo total-body irradiation

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Tacrolimus: Given IV or PO

Mycophenolate Mofetil: Given PO

Patients receive tacrolimus IV or PO every 12 hours on days -3 to 150 with taper beginning on day 100 in the absence of GVHD. Patients also receive MMF PO every 8 hours on days 0-29 and then every 12 hours on days 30-180 with taper beginning on day 150 in the absence of GVHD.

Fludarabine Phosphate: Given IV

Total-Body Irradiation: Undergo total-body irradiation

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Tacrolimus: Given IV or PO

Mycophenolate Mofetil: Given PO

Patients receive tacrolimus and MMF as in arm II. Patients also receive sirolimus PO once daily on days -3 to 80.

Fludarabine Phosphate: Given IV

Total-Body Irradiation: Undergo total-body irradiation

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Tacrolimus: Given IV or PO

Mycophenolate Mofetil: Given PO

Sirolimus: Given PO

Overall Number of Participants Analyzed 70 71 69
Measure Type: Number
Unit of Measure: percentage of participants
Day 180 89 79 84
1 Year 70 66 59
2 Year 53 45 45
3 Year 49 38 41
4 Year 46 37 36
5 Year 40 32 35
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I (MMF and Tacrolimus), Arm II (MMF and Tacrolimus Alternate Schedule), Arm III (MMF, Tacrolimus, and Sirolimus)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.93
Comments Overall test of homogeneity among arms, reflecting events over the entire period of follow-up
Method Regression, Cox
Comments [Not Specified]
5.Secondary Outcome
Title Progression-free Survival
Hide Description

Percentage of patients with progression-free survival, estimated by cumulative incidence methods

Cumulative incidence methods are the standard way to estimate incidence of an endpoint in the presence of competing risks and censoring (ref)” Here is the reference. Gooley TA, Leisenring W, Crowley J, Storer BE: Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Statistics in Medicine 18:695-706, 1999. PMID 10204198

Time Frame At 6 months and then every year thereafter, up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I (MMF and Tacrolimus) Arm II (MMF and Tacrolimus Alternate Schedule) Arm III (MMF, Tacrolimus, and Sirolimus)
Hide Arm/Group Description:

Patients receive tacrolimus IV or PO every 12 hours on days -3 to 180 with taper beginning on day 100 in the absence of GVHD. Patients also receive MMF PO every 8 hours on days 0-29 and then every 12 hours on days 30-96 with taper beginning on day 40 in the absence of GVHD.

Fludarabine Phosphate: Given IV

Total-Body Irradiation: Undergo total-body irradiation

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Tacrolimus: Given IV or PO

Mycophenolate Mofetil: Given PO

Patients receive tacrolimus IV or PO every 12 hours on days -3 to 150 with taper beginning on day 100 in the absence of GVHD. Patients also receive MMF PO every 8 hours on days 0-29 and then every 12 hours on days 30-180 with taper beginning on day 150 in the absence of GVHD.

Fludarabine Phosphate: Given IV

Total-Body Irradiation: Undergo total-body irradiation

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Tacrolimus: Given IV or PO

Mycophenolate Mofetil: Given PO

Patients receive tacrolimus and MMF as in arm II. Patients also receive sirolimus PO once daily on days -3 to 80.

Fludarabine Phosphate: Given IV

Total-Body Irradiation: Undergo total-body irradiation

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Tacrolimus: Given IV or PO

Mycophenolate Mofetil: Given PO

Sirolimus: Given PO

Overall Number of Participants Analyzed 70 71 69
Measure Type: Number
Unit of Measure: percentage of participants
Day 180 77 66 65
1 Year 61 54 48
2 Year 41 38 38
3 Year 39 32 35
4 Year 33 31 33
5 Year 30 28 32
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I (MMF and Tacrolimus), Arm II (MMF and Tacrolimus Alternate Schedule), Arm III (MMF, Tacrolimus, and Sirolimus)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.96
Comments Overall test of homogeneity among arms, reflecting events over the entire period of follow-up
Method Regression, Cox
Comments [Not Specified]
Time Frame AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Arm I (MMF and Tacrolimus) Arm II (MMF and Tacrolimus Alternate Schedule) Arm III (MMF, Tacrolimus, and Sirolimus)
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Patients receive tacrolimus IV or PO every 12 hours on days -3 to 180 with taper beginning on day 100 in the absence of GVHD. Patients also receive MMF PO every 8 hours on days 0-29 and then every 12 hours on days 30-96 with taper beginning on day 40 in the absence of GVHD.

Fludarabine Phosphate: Given IV

Total-Body Irradiation: Undergo total-body irradiation

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Tacrolimus: Given IV or PO

Mycophenolate Mofetil: Given PO

Patients receive tacrolimus IV or PO every 12 hours on days -3 to 150 with taper beginning on day 100 in the absence of GVHD. Patients also receive MMF PO every 8 hours on days 0-29 and then every 12 hours on days 30-180 with taper beginning on day 150 in the absence of GVHD.

Fludarabine Phosphate: Given IV

Total-Body Irradiation: Undergo total-body irradiation

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Tacrolimus: Given IV or PO

Mycophenolate Mofetil: Given PO

Patients receive tacrolimus and MMF as in arm II. Patients also receive sirolimus PO once daily on days -3 to 80.

Fludarabine Phosphate: Given IV

Total-Body Irradiation: Undergo total-body irradiation

Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplantation

Tacrolimus: Given IV or PO

Mycophenolate Mofetil: Given PO

Sirolimus: Given PO

All-Cause Mortality
Arm I (MMF and Tacrolimus) Arm II (MMF and Tacrolimus Alternate Schedule) Arm III (MMF, Tacrolimus, and Sirolimus)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Arm I (MMF and Tacrolimus) Arm II (MMF and Tacrolimus Alternate Schedule) Arm III (MMF, Tacrolimus, and Sirolimus)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/70 (14.29%)      10/71 (14.08%)      7/69 (10.14%)    
Cardiac disorders       
Pericardial effusion   0/70 (0.00%)  0 1/71 (1.41%)  1 0/69 (0.00%)  0
Hypertension   0/70 (0.00%)  0 0/71 (0.00%)  0 1/69 (1.45%)  1
Gastrointestinal disorders       
Intestinal pneumatosis   1/70 (1.43%)  1 0/71 (0.00%)  0 0/69 (0.00%)  0
General disorders       
Toxic leukoencephalopathy, infections w/ pneumonia and pyelonephritis   1/70 (1.43%)  1 0/71 (0.00%)  0 0/69 (0.00%)  0
Multi-organ failure   0/70 (0.00%)  0 1/71 (1.41%)  1 1/69 (1.45%)  1
Hepatobiliary disorders       
Hepatic   1/70 (1.43%)  1 0/71 (0.00%)  0 0/69 (0.00%)  0
Immune system disorders       
GvHD w/ infection   1/70 (1.43%)  1 1/71 (1.41%)  1 1/69 (1.45%)  1
GVHD   0/70 (0.00%)  0 0/71 (0.00%)  0 2/69 (2.90%)  2
Infections and infestations       
Respiratory infection   1/70 (1.43%)  1 3/71 (4.23%)  3 0/69 (0.00%)  0
Sepsis   1/70 (1.43%)  1 1/71 (1.41%)  1 1/69 (1.45%)  1
Mucormycosis   0/70 (0.00%)  0 1/71 (1.41%)  1 0/69 (0.00%)  0
Injury, poisoning and procedural complications       
Severe hemoptysis   1/70 (1.43%)  1 0/71 (0.00%)  0 0/69 (0.00%)  0
Renal and urinary disorders       
Renal insufficiency   0/70 (0.00%)  0 0/71 (0.00%)  0 1/69 (1.45%)  1
Respiratory, thoracic and mediastinal disorders       
Pulmonary   0/70 (0.00%)  0 1/71 (1.41%)  1 0/69 (0.00%)  0
Vascular disorders       
Thrombosis   2/70 (2.86%)  2 1/71 (1.41%)  1 0/69 (0.00%)  0
CNS cerebrovascular ischemia   1/70 (1.43%)  1 0/71 (0.00%)  0 0/69 (0.00%)  0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Arm I (MMF and Tacrolimus) Arm II (MMF and Tacrolimus Alternate Schedule) Arm III (MMF, Tacrolimus, and Sirolimus)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   35/70 (50.00%)      33/71 (46.48%)      41/69 (59.42%)    
Blood and lymphatic system disorders       
Blood/Bone Marrow   3/70 (4.29%)  3 4/71 (5.63%)  6 2/69 (2.90%)  2
Coagulation   0/70 (0.00%)  0 0/71 (0.00%)  0 1/69 (1.45%)  1
Cardiac disorders       
Cardiovascular   8/70 (11.43%)  9 3/71 (4.23%)  5 3/69 (4.35%)  4
Gastrointestinal disorders       
Gastrointestinal   9/70 (12.86%)  10 2/71 (2.82%)  2 7/69 (10.14%)  8
General disorders       
Constitutional Symptoms   1/70 (1.43%)  1 2/71 (2.82%)  2 1/69 (1.45%)  1
Pain   1/70 (1.43%)  1 1/71 (1.41%)  1 0/69 (0.00%)  0
Hepatobiliary disorders       
Hepatic   1/70 (1.43%)  1 2/71 (2.82%)  2 1/69 (1.45%)  1
Infections and infestations       
Infection/Febrile Neutropenia   0/70 (0.00%)  0 4/71 (5.63%)  4 2/69 (2.90%)  2
Metabolism and nutrition disorders       
Metabolic/Laboratory   1/70 (1.43%)  1 1/71 (1.41%)  1 2/69 (2.90%)  2
Musculoskeletal and connective tissue disorders       
Musculoskelatal   0/70 (0.00%)  0 2/71 (2.82%)  2 1/69 (1.45%)  3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Secondary Malignancy   1/70 (1.43%)  1 0/71 (0.00%)  0 0/69 (0.00%)  0
Nervous system disorders       
Neurology   2/70 (2.86%)  2 1/71 (1.41%)  1 6/69 (8.70%)  11
Renal and urinary disorders       
Renal/Genitourinary   1/70 (1.43%)  2 2/71 (2.82%)  2 5/69 (7.25%)  5
Respiratory, thoracic and mediastinal disorders       
Pulmonary   6/70 (8.57%)  6 8/71 (11.27%)  9 8/69 (11.59%)  8
Skin and subcutaneous tissue disorders       
Dermatology/Skin   0/70 (0.00%)  0 1/71 (1.41%)  1 1/69 (1.45%)  1
Vascular disorders       
Hemorrhage   1/70 (1.43%)  1 0/71 (0.00%)  0 1/69 (1.45%)  1
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Brenda M. Sandmaier
Organization: Fred Hutchinson Cancer Research Center
Phone: (206) 667-4961
EMail: bsandmai@fhcrc.org
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Responsible Party: Brenda Sandmaier, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00105001     History of Changes
Other Study ID Numbers: 1938.00
NCI-2010-00268 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
1938.00 ( Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
P01CA018029 ( U.S. NIH Grant/Contract )
First Submitted: March 3, 2005
First Posted: March 4, 2005
Results First Submitted: August 13, 2015
Results First Posted: September 15, 2015
Last Update Posted: March 8, 2018