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Allogeneic Transplantation Using Total Lymphoid Irradiation (TLI) and Anti-Thymocyte Globulin (ATG) for Older Patients With Hematologic Malignancies

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ClinicalTrials.gov Identifier: NCT00185640
Recruitment Status : Completed
First Posted : September 16, 2005
Results First Posted : October 3, 2017
Last Update Posted : October 3, 2017
Sponsor:
Information provided by (Responsible Party):
Robert Lowsky, Stanford University

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Blood Cancer
Leukemia
Interventions Drug: Cyclosporine
Drug: Anti-Thymocyte Globulin
Drug: mycophenolate mofetil
Drug: Granulocyte-Colony Stimulating Factor
Radiation: Total Lymphoid Irradiation
Enrollment 303
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Non-myeloablative Transplantation
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Cyclosporine: 3 to 5 mg/kg twice-a-day (BID); intravenous (IV) or oral

Thymoglobulin: 7.5 to 10 mg/kg; IV

Mycophenolate mofetil: 15 mg/kg BID or Q 8 hours

G-CSF: 16 mcg/kg; subcutaneous (SQ)

Period Title: Overall Study
Started 303
Transplanted 296
90 Days Post-transplant 161
Completed 158
Not Completed 145
Reason Not Completed
Not Eligible             4
Withdrawal by Subject             3
Death             138
Arm/Group Title Non-myeloablative Transplantation
Hide Arm/Group Description

Cyclosporine: 3 to 5 mg/kg BID; IV or oral

Thymoglobulin: 7.5 to 10 mg/kg; IV

Mycophenolate mofetil: 15 mg/kg BID or Q 8 hours

G-CSF: 16 mcg/kg; SQ

Overall Number of Baseline Participants 303
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 303 participants
<=18 years
0
   0.0%
Between 18 and 65 years
260
  85.8%
>=65 years
43
  14.2%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 303 participants
Female
128
  42.2%
Male
175
  57.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 303 participants
Hispanic or Latino
20
   6.6%
Not Hispanic or Latino
276
  91.1%
Unknown or Not Reported
7
   2.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 303 participants
American Indian or Alaska Native
0
   0.0%
Asian
37
  12.2%
Native Hawaiian or Other Pacific Islander
7
   2.3%
Black or African American
6
   2.0%
White
233
  76.9%
More than one race
0
   0.0%
Unknown or Not Reported
20
   6.6%
Histology  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 303 participants
Acute Biphenotypic Leukemia 1
Acute Leukemia, Nos 1
Acute Monocytic Leukemia 2
Acute Myeloid Leukemia 84
Acute Promyelocytic Leukemia 4
Angioimmunoblastic T-Cell Lymphoma 1
B lymphoblastic leukemia/lymphoma, NOS 1
B-Cell Chr. Lymph. Leuk./Small Lymph. Lymphoma 45
Chronic Myelogenous Leukemia, Bcr/Abl Positive 1
Chronic Myeloid Leukemia, Nos 8
Chronic Myeloproliferative Disease, Nos 2
Cutaneous T-Cell Lymphoma, Nos 1
Follicular Lymphoma, Grade 1-3 4
Hodgkin Lymphoma, Nodular Sclerosis, Nos 4
Hodgkin Lymphoma, Nos 20
Malignant Lymphoma, Non-Hodgkin 86
Mantle Cell Lymphoma 10
Marginal Zone B-Cell Lymphoma, Nos 2
Mature T-Cell Lymphoma, Nos 1
Ml, Large B-Cell, Diffuse 2
Ml, Small B Lymphocytic, Nos 1
Myelodysplastic Syndrome, Nos 3
Precursor Cell Lymphoblastic Leukemia, Nos 15
Prolymphocytic Leukemia, Nos 1
Prolymphocytic Leukemia, T-Cell Type 1
Subcutaneous Panniculitis-Like T-Cell Lymphoma 1
Unknown 1
1.Primary Outcome
Title Acute Graft vs Host Disease (GvHD)
Hide Description

The incidence of acute GvHD after transplantation was assessed per Glucksberg GvHD grade, a compound scale based on the following combinations of disease stages.

Skin manifestations Skin Stages

  • 0: No rash
  • 1: Maculopapular (MP) rash <25% of body surface area
  • 2: MP rash on 25-50% of body surface area
  • 3: Generalized erythroderma (ED)
  • 4: Generalized ED with bullous formation and desquamation

Liver Stages (Bilirubin in mg/dL)

  • 0: <2
  • 1: 2-3
  • 2: 3.01-6
  • 3: 6.01-15.0
  • 4: >15

Gastrointestinal (GI) Stages (diarrhea)

  • 0: None or < 500 mL/day
  • 1: 500-999 mL/day
  • 2: 1000-1499 mL/day
  • 3: >1500 mL/day
  • 4: Severe abdominal pain, with or without ileus

Glucksberg Overall grade

  • Grade 1: Skin 1/2; GI 0; Liver 0; Karnofsky performance scale (KPS) 90-100%.
  • Grade 2: Skin 1-3; GI 1; Liver 1; KPS 70-80
  • Grade 2: Skin 2/3; GI 2/3; Liver 2-4; KPS 50-60
  • Grade 4: Skin 2-4; GI 2-4; Liver 2-4; KPS 30-40
Time Frame 100 days post-transplant
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Reports the incidence of Grades 2 to 4 acute GvHD, as observed for the initial 37 participants treated on this study, who constitute the Primary Analysis for the study. See linked citation Lowsky, et al. NEJM. 29Sep2005;353(13)1321-1331.
Arm/Group Title Non-myeloablative Transplantation
Hide Arm/Group Description:

Cyclosporine: 3 to 5 mg/kg BID; IV or oral

Thymoglobulin: 7.5 to 10 mg/kg; IV

Mycophenolate mofetil: 15 mg/kg BID or Q 8 hours

G-CSF: 16 mcg/kg; SQ

Overall Number of Participants Analyzed 37
Measure Type: Number
Unit of Measure: percentage of participants
2.7
2.Secondary Outcome
Title Acute Graft vs Host Disease (GvHD), All Evaluable
Hide Description

The incidence of acute GvHD after transplantation was assessed per Glucksberg GvHD grade, a compound scale based on the following combinations of disease stages.

Skin manifestations Skin Stages

  • 0: No rash
  • 1: Maculopapular (MP) rash <25% of body surface area
  • 2: MP rash on 25-50% of body surface area
  • 3: Generalized erythroderma (ED)
  • 4: Generalized ED with bullous formation and desquamation

Liver Stages (Bilirubin in mg/dL)

  • 0: <2
  • 1: 2-3
  • 2: 3.01-6
  • 3: 6.01-15.0
  • 4: >15

Gastrointestinal (GI) Stages (diarrhea)

  • 0: None or < 500 mL/day
  • 1: 500-999 mL/day
  • 2: 1000-1499 mL/day
  • 3: >1500 mL/day
  • 4: Severe abdominal pain, with or without ileus

Glucksberg Overall grade

  • Grade 1: Skin 1/2; GI 0; Liver 0; Karnofsky performance scale (KPS) 90-100%.
  • Grade 2: Skin 1-3; GI 1; Liver 1; KPS 70-80
  • Grade 2: Skin 2/3; GI 2/3; Liver 2-4; KPS 50-60
  • Grade 4: Skin 2-4; GI 2-4; Liver 2-4; KPS 30-40
Time Frame 100 days post-transplant
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Non-myeloablative Transplantation
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Cyclosporine: 3 to 5 mg/kg BID; IV or oral

Thymoglobulin: 7.5 to 10 mg/kg; IV

Mycophenolate mofetil: 15 mg/kg BID or Q 8 hours

G-CSF: 16 mcg/kg; SQ

Overall Number of Participants Analyzed 303
Measure Type: Number
Unit of Measure: percentage of participants
11
3.Secondary Outcome
Title Incidence of Relapse
Hide Description Reports the overall rate of disease relapse, occurring any time within 3 years after transplant
Time Frame 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Non-myeloablative Transplantation
Hide Arm/Group Description:

Cyclosporine: 3 to 5 mg/kg BID; IV or oral

Thymoglobulin: 7.5 to 10 mg/kg; IV

Mycophenolate mofetil: 15 mg/kg BID or Q 8 hours

G-CSF: 16 mcg/kg; SQ

Overall Number of Participants Analyzed 303
Measure Type: Number
Unit of Measure: percentage of participants
53
4.Secondary Outcome
Title Overall Survival (OS)
Hide Description [Not Specified]
Time Frame 3 and 5 years
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Non-myeloablative Transplantation
Hide Arm/Group Description:

Cyclosporine: 3 to 5 mg/kg BID; IV or oral

Thymoglobulin: 7.5 to 10 mg/kg; IV

Mycophenolate mofetil: 15 mg/kg BID or Q 8 hours

G-CSF: 16 mcg/kg; SQ

Overall Number of Participants Analyzed 303
Measure Type: Number
Unit of Measure: percentage of participants
3 years 70
5 years 64
5.Secondary Outcome
Title Event-free Survival (EFS)
Hide Description Reports the proportion of subjects who neither died due to any cause nor experienced relapse.
Time Frame 3 and 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Non-myeloablative Transplantation
Hide Arm/Group Description:

Cyclosporine: 3 to 5 mg/kg BID; IV or oral

Thymoglobulin: 7.5 to 10 mg/kg; IV

Mycophenolate mofetil: 15 mg/kg BID or Q 8 hours

G-CSF: 16 mcg/kg; SQ

Overall Number of Participants Analyzed 303
Measure Type: Number
Unit of Measure: percentage of participants
3 years 44
5 years 38
6.Secondary Outcome
Title Transplant-related Mortality
Hide Description Reports the proportion of participants who expired within 1 year due to any complication or failure of the transplant.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Non-myeloablative Transplantation
Hide Arm/Group Description:

Cyclosporine: 3 to 5 mg/kg BID; IV or oral

Thymoglobulin: 7.5 to 10 mg/kg; IV

Mycophenolate mofetil: 15 mg/kg BID or Q 8 hours

G-CSF: 16 mcg/kg; SQ

Overall Number of Participants Analyzed 303
Measure Type: Number
Unit of Measure: percentage of participants
6
Time Frame 5 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Non-myeloablative Transplantation
Hide Arm/Group Description Per the Common Rule, adverse events other than death, secondary malignancy, or relapse were not collected.
All-Cause Mortality
Non-myeloablative Transplantation
Affected / at Risk (%)
Total   0/303 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Non-myeloablative Transplantation
Affected / at Risk (%) # Events
Total   138/303 (45.54%)    
Gastrointestinal disorders   
Deaths *  138/303 (45.54%) 
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Non-myeloablative Transplantation
Affected / at Risk (%) # Events
Total   55/303 (18.15%)    
Blood and lymphatic system disorders   
Secondary malignancy *  22/303 (7.26%)  22
Gastrointestinal disorders   
Secondary malignancy *  4/303 (1.32%)  4
Reproductive system and breast disorders   
Secondary malignancy *  2/303 (0.66%)  2
Respiratory, thoracic and mediastinal disorders   
Secondary malignancy *  1/303 (0.33%)  1
Skin and subcutaneous tissue disorders   
Secondary malignancy *  26/303 (8.58%)  26
*
Indicates events were collected by non-systematic assessment
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.
Results Point of Contact
Name/Title: Robert Lowsky
Organization: Stanford University
Phone: 650-723-0822
Publications of Results:
Responsible Party: Robert Lowsky, Stanford University
ClinicalTrials.gov Identifier: NCT00185640     History of Changes
Obsolete Identifiers: NCT00186615
Other Study ID Numbers: IRB-11960
78998 ( Other Identifier: Stanford University Alternate IRB Approval Number )
BMT153 ( Other Identifier: OnCore )
First Submitted: September 12, 2005
First Posted: September 16, 2005
Results First Submitted: December 1, 2016
Results First Posted: October 3, 2017
Last Update Posted: October 3, 2017