Allogeneic Transplantation Using Total Lymphoid Irradiation (TLI) and Anti-Thymocyte Globulin (ATG) for Older Patients With Hematologic Malignancies
Study Details
Study Description
Brief Summary
To measure how frequently and to what degree a complication of transplant cell acute graft versus host disease (GvHD) occurs.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
This study evaluated whether TLI-ATG conditioning followed by allogeneic hematpoietic cell transplant (HCT), which has provided excellent overall survival for patients with relapsed lymphoma after failed autologous HCT, provides a similar benefit in the setting of elderly patients with hematologic malignancies.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Non-myeloablative transplantation Pre-transplant total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) infusion with Day 0 allogeneic hematopoietic cell transplant (HCT), followed by post-transplant immunosuppression by cyclosporine and mycophenolate mofetil. |
Drug: Cyclosporine
Starting day -3 at a dose of 5 mg/kg orally twice daily with a target trough level of 350 to 450 ng/mL
Other Names:
Drug: Anti-thymocyte globulin (ATG)
1.5 mg/kg for total dose of 7.5mg/kg, IV starting on day -11 to day -7 before HCT
Other Names:
Drug: Mycophenolate mofetil (MMF)
Begins on day 0 after HCT at a dose of 15 mg/kg. Transplant recipients who received related donor grafts received MMF twice daily and those who received unrelated donor grafts received MMF 3 times daily.
Other Names:
Drug: Filgrastim
Donors mobilized with 16 µg/kg/day filgrastim.
As needed, myelosuppression in transplant recipients will be managed with subcutaneous filgrastim 5 µg/kg/day
Other Names:
Radiation: Total Lymphoid Irradiation (TLI)
0.8 Gy/day from day -11 to day -7 (inclusive) from day -4 to day -2 (inclusive) with 2 additional fractions of 0.8 Gy delivered on day -1 for total dose of 8 Gy.
|
Outcome Measures
Primary Outcome Measures
- Acute Graft vs Host Disease (GvHD) [100 days post-transplant]
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 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
Secondary Outcome Measures
- Acute Graft vs Host Disease (GvHD), All Evaluable [100 days post-transplant]
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 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
- Incidence of Relapse [3 years]
Reports the overall rate of disease relapse, occurring any time within 3 years after transplant
- Overall Survival (OS) [3 and 5 years]
- Event-free Survival (EFS) [3 and 5 years]
Reports the number and proportion of participants who neither died due to any cause nor experienced relapse.
- Transplant-related Mortality [1 year]
Reports the proportion of participants who expired within 1 year due to any complication or failure of the transplant.
Eligibility Criteria
Criteria
INCLUSION CRITERIA:
-
Any patient with one of the following hematolymphoid malignancies or syndromes in whom allogeneic hematopoietic stem cell transplant (HST) is warranted. Specific disease categories include:
-
Indolent advanced stage non-Hodgkin lymphomas
-
Mantle cell lymphoma
-
Chronic lymphocytic leukemia
-
Hodgkin disease (Hodgkin's lymphoma)
-
Acute leukemias in complete remission
-
Aplastic anemia
-
Paroxysmal nocturnal hemoglobinuria
-
Myelodysplastic or myeloproliferative syndromes.
-
Other selected malignancies/disorders may also be considered but must be approved by the transplant team and the Principal Investigator.
-
Age > 50 years, or if < 50 years of age, considered to be at high risk for regimen-related toxicity associated with conventional myeloablative transplants due to pre-existing medical conditions or prior therapy.
-
A fully human leukocyte antigen (HLA)-identical sibling or matched unrelated donor is available. Potential participants with one antigen mismatched donors can be considered but only after discussion with the transplant team and the Principal Investigator.
-
Participant must be competent to give consent.
EXCLUSION CRITERIA:
-
Progressive hematolymphoid malignancies despite conventional therapies, or acute leukemias not in complete remission.
-
Uncontrolled central nervous system (CNS) involvement with disease
-
Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
-
Pregnant
-
Cardiac ejection fraction < 30%
-
Uncontrolled cardiac failure
-
Pulmonary diffusing capacity (DLCO) < 40% predicted
-
Elevation of bilirubin to > 3 mg/dL
-
Transaminases > 4 x the upper limit of normal
-
Creatinine clearance < 50 cc/min (24-hour urine collection)
-
Karnofsky performance score < 60%
-
Poorly controlled hypertension on multiple antihypertensives
-
Documented fungal disease that is progressive despite treatment
-
HIV-positive. Other viral infections, ie, Hepatitis B- and C- positive, evaluated on a case-by-case basis
-
Psychiatric disorders or psychosocial problems which in the opinion of the primary physician or Principal Investigator would place the patient at unacceptable risk from this regimen.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Stanford University School of Medicine | Stanford | California | United States | 94305 |
Sponsors and Collaborators
- Stanford University
Investigators
- Principal Investigator: Robert Lowsky, Stanford University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRB-11960
- 78998
- BMT153
- NCT00186615
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Non-myeloablative Transplantation |
---|---|
Arm/Group Description | Pre-transplant total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) infusion with Day 0 allogeneic hematopoietic cell transplant (HCT), followed by post-transplant immunosuppression by cyclosporine and mycophenolate mofetil |
Period Title: Overall Study | |
STARTED | 303 |
Transplanted | 296 |
90 Days Post-transplant | 161 |
COMPLETED | 158 |
NOT COMPLETED | 145 |
Baseline Characteristics
Arm/Group Title | Non-myeloablative Transplantation |
---|---|
Arm/Group Description | Pre-transplant total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) infusion with Day 0 allogeneic hematopoietic cell transplant (HCT), followed by post-transplant immunosuppression by cyclosporine and mycophenolate mofetil |
Overall Participants | 303 |
Age (Count of Participants) | |
<=18 years |
0
0%
|
Between 18 and 65 years |
260
85.8%
|
>=65 years |
43
14.2%
|
Sex: Female, Male (Count of Participants) | |
Female |
128
42.2%
|
Male |
175
57.8%
|
Ethnicity (NIH/OMB) (Count of Participants) | |
Hispanic or Latino |
20
6.6%
|
Not Hispanic or Latino |
276
91.1%
|
Unknown or Not Reported |
7
2.3%
|
Race (NIH/OMB) (Count of Participants) | |
American Indian or Alaska Native |
0
0%
|
Asian |
37
12.2%
|
Native Hawaiian or Other Pacific Islander |
7
2.3%
|
Black or African American |
6
2%
|
White |
233
76.9%
|
More than one race |
0
0%
|
Unknown or Not Reported |
20
6.6%
|
Histology (participants) [Number] | |
Acute Biphenotypic Leukemia |
1
0.3%
|
Acute Leukemia, Nos |
1
0.3%
|
Acute Monocytic Leukemia |
2
0.7%
|
Acute Myeloid Leukemia |
84
27.7%
|
Acute Promyelocytic Leukemia |
4
1.3%
|
Angioimmunoblastic T-Cell Lymphoma |
1
0.3%
|
B lymphoblastic leukemia/lymphoma, NOS |
1
0.3%
|
B-Cell Chr. Lymph. Leuk./Small Lymph. Lymphoma |
45
14.9%
|
Chronic Myelogenous Leukemia, Bcr/Abl Positive |
1
0.3%
|
Chronic Myeloid Leukemia, Nos |
8
2.6%
|
Chronic Myeloproliferative Disease, Nos |
2
0.7%
|
Cutaneous T-Cell Lymphoma, Nos |
1
0.3%
|
Follicular Lymphoma, Grade 1-3 |
4
1.3%
|
Hodgkin Lymphoma, Nodular Sclerosis, Nos |
4
1.3%
|
Hodgkin Lymphoma, Nos |
20
6.6%
|
Malignant Lymphoma, Non-Hodgkin |
86
28.4%
|
Mantle Cell Lymphoma |
10
3.3%
|
Marginal Zone B-Cell Lymphoma, Nos |
2
0.7%
|
Mature T-Cell Lymphoma, Nos |
1
0.3%
|
Ml, Large B-Cell, Diffuse |
2
0.7%
|
Ml, Small B Lymphocytic, Nos |
1
0.3%
|
Myelodysplastic Syndrome, Nos |
3
1%
|
Precursor Cell Lymphoblastic Leukemia, Nos |
15
5%
|
Prolymphocytic Leukemia, Nos |
1
0.3%
|
Prolymphocytic Leukemia, T-Cell Type |
1
0.3%
|
Subcutaneous Panniculitis-Like T-Cell Lymphoma |
1
0.3%
|
Unknown |
1
0.3%
|
Outcome Measures
Title | Acute Graft vs Host Disease (GvHD) |
---|---|
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 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 |
Outcome Measure Data
Analysis Population Description |
---|
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 |
---|---|
Arm/Group Description | Pre-transplant total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) infusion with Day 0 allogeneic hematopoietic cell transplant (HCT), followed by post-transplant immunosuppression by cyclosporine and mycophenolate mofetil. |
Measure Participants | 37 |
Number [percentage of participants] |
2.7
0.9%
|
Title | Acute Graft vs Host Disease (GvHD), All Evaluable |
---|---|
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 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 |
Outcome Measure Data
Analysis Population Description |
---|
Reports data for all evaluable participants |
Arm/Group Title | Non-myeloablative Transplantation |
---|---|
Arm/Group Description | Pre-transplant total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) infusion with Day 0 allogeneic hematopoietic cell transplant (HCT), followed by post-transplant immunosuppression by cyclosporine and mycophenolate mofetil. |
Measure Participants | 303 |
Number [percentage of participants] |
11
3.6%
|
Title | Incidence of Relapse |
---|---|
Description | Reports the overall rate of disease relapse, occurring any time within 3 years after transplant |
Time Frame | 3 years |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Non-myeloablative Transplantation |
---|---|
Arm/Group Description | Pre-transplant total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) infusion with Day 0 allogeneic hematopoietic cell transplant (HCT), followed by post-transplant immunosuppression by cyclosporine and mycophenolate mofetil. |
Measure Participants | 303 |
Number [percentage of participants] |
53
17.5%
|
Title | Overall Survival (OS) |
---|---|
Description | |
Time Frame | 3 and 5 years |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Non-myeloablative Transplantation |
---|---|
Arm/Group Description | Pre-transplant total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) infusion with Day 0 allogeneic hematopoietic cell transplant (HCT), followed by post-transplant immunosuppression by cyclosporine and mycophenolate mofetil. |
Measure Participants | 303 |
3 years |
70
23.1%
|
5 years |
64
21.1%
|
Title | Event-free Survival (EFS) |
---|---|
Description | Reports the number and proportion of participants who neither died due to any cause nor experienced relapse. |
Time Frame | 3 and 5 years |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Non-myeloablative Transplantation |
---|---|
Arm/Group Description | Pre-transplant total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) infusion with Day 0 allogeneic hematopoietic cell transplant (HCT), followed by post-transplant immunosuppression by cyclosporine and mycophenolate mofetil. |
Measure Participants | 303 |
3 years |
44
14.5%
|
5 years |
38
12.5%
|
Title | Transplant-related Mortality |
---|---|
Description | Reports the proportion of participants who expired within 1 year due to any complication or failure of the transplant. |
Time Frame | 1 year |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Non-myeloablative Transplantation |
---|---|
Arm/Group Description | Pre-transplant total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) infusion with Day 0 allogeneic hematopoietic cell transplant (HCT), followed by post-transplant immunosuppression by cyclosporine and mycophenolate mofetil. |
Measure Participants | 303 |
Number [percentage of participants] |
6
2%
|
Adverse Events
Time Frame | 5 years | |
---|---|---|
Adverse Event Reporting Description | Adverse events other than death, secondary malignancy, or relapse were not collected. | |
Arm/Group Title | Non-myeloablative Transplantation | |
Arm/Group Description | ||
All Cause Mortality |
||
Non-myeloablative Transplantation | ||
Affected / at Risk (%) | # Events | |
Total | 138/303 (45.5%) | |
Serious Adverse Events |
||
Non-myeloablative Transplantation | ||
Affected / at Risk (%) | # Events | |
Total | 138/303 (45.5%) | |
Gastrointestinal disorders | ||
Deaths | 138/303 (45.5%) | |
Other (Not Including Serious) Adverse Events |
||
Non-myeloablative Transplantation | ||
Affected / at Risk (%) | # Events | |
Total | 55/303 (18.2%) | |
Blood and lymphatic system disorders | ||
Secondary malignancy | 22/303 (7.3%) | 22 |
Gastrointestinal disorders | ||
Secondary malignancy | 4/303 (1.3%) | 4 |
Reproductive system and breast disorders | ||
Secondary malignancy | 2/303 (0.7%) | 2 |
Respiratory, thoracic and mediastinal disorders | ||
Secondary malignancy | 1/303 (0.3%) | 1 |
Skin and subcutaneous tissue disorders | ||
Secondary malignancy | 26/303 (8.6%) | 26 |
Limitations/Caveats
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.
Results Point of Contact
Name/Title | Robert Lowsky |
---|---|
Organization | Stanford University |
Phone | 650-723-0822 |
rlowsky@stanford.edu |
- IRB-11960
- 78998
- BMT153
- NCT00186615