Trial Outcomes & Findings for Allogeneic HCT With HLA-matched Donors : a Phase II Randomized Study Comparing 2 Nonmyeloablative Conditionings (NCT NCT00603954)
NCT ID: NCT00603954
Last Updated: 2022-01-26
Results Overview
Percentage of participants with aGVHD according grades: Grade I: rash skin \< 25 % area; bilirubin: 20-30 mg/ml; diarrhea: 500-1000 ml/day Grade II: rash skin 25-50 % area; bilirubin: 30-60 mg/ml; diarrhea: 10000-1500 ml/day Grade III:rash skin \> 50 % area; bilirubin: 60-150 mg/ml; diarrhea: \>1500 ml/day Grade IV: erythroderma; bilirubin: \> 150 mg/ml; diarrhea: \>2000 ml/day Grade IV is the worst grade Patients given a second allogeneic HCT were censured for GVHD analyses.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
107 participants
Primary outcome timeframe
180 days after HCT
Results posted on
2022-01-26
Participant Flow
Participant milestones
| Measure |
Flu-TBI
Conditioning regimen consisting of fludarabine 30 mg/m2 on days -4, -3 and -2 (total dose 90 mg/m2), followed by a singe dose of 2 Gy TBI administered on day 0, at a low dose-rate (≈ 7 cGy/min), before infusion of cells.
Conditioning regimen TBI + Fludarabine: 2 Gy TBI, Fludarabine 90 mg/m²
|
TLI-ATG
Conditioning consisting of 8 Gy TLI and ATG. TLI will be administered by linear accelerator at a dose of 80 cGy daily, starting 11 days before transplantation, until a total of 10 doses (800 cGy) has been delivered. The irradiation will consist of a supradiaphragmatic mantle field, a subdiaphragmatic field including an inverted Y and splenic ports, encompassing all major lymphoid organs, including the thymus, spleen, and lymph nodes, as used in the treatment of Hodgkin's disease (Kaplan HS, Cancer Research 26:1268-1276, 1966). The Waldeyer ring is not included. ATG (Thymoglobulin®, Genzyme), at a dose of 1.5 mg/kg/d, will be given intravenously on days -11 through -7.
Conditioning regimen II (TLI 8 Gy + ATG \[Thymoglobulin\]): TLI 8 Gy + ATG (Thymoglobulin) 7.5 mg/kg
|
|---|---|---|
|
Overall Study
STARTED
|
50
|
47
|
|
Overall Study
COMPLETED
|
49
|
45
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
Flu-TBI
Conditioning regimen consisting of fludarabine 30 mg/m2 on days -4, -3 and -2 (total dose 90 mg/m2), followed by a singe dose of 2 Gy TBI administered on day 0, at a low dose-rate (≈ 7 cGy/min), before infusion of cells.
Conditioning regimen TBI + Fludarabine: 2 Gy TBI, Fludarabine 90 mg/m²
|
TLI-ATG
Conditioning consisting of 8 Gy TLI and ATG. TLI will be administered by linear accelerator at a dose of 80 cGy daily, starting 11 days before transplantation, until a total of 10 doses (800 cGy) has been delivered. The irradiation will consist of a supradiaphragmatic mantle field, a subdiaphragmatic field including an inverted Y and splenic ports, encompassing all major lymphoid organs, including the thymus, spleen, and lymph nodes, as used in the treatment of Hodgkin's disease (Kaplan HS, Cancer Research 26:1268-1276, 1966). The Waldeyer ring is not included. ATG (Thymoglobulin®, Genzyme), at a dose of 1.5 mg/kg/d, will be given intravenously on days -11 through -7.
Conditioning regimen II (TLI 8 Gy + ATG \[Thymoglobulin\]): TLI 8 Gy + ATG (Thymoglobulin) 7.5 mg/kg
|
|---|---|---|
|
Overall Study
Protocol Violation
|
1
|
2
|
Baseline Characteristics
Allogeneic HCT With HLA-matched Donors : a Phase II Randomized Study Comparing 2 Nonmyeloablative Conditionings
Baseline characteristics by cohort
| Measure |
Flu-TBI
n=49 Participants
Conditioning regimen consisting of fludarabine 30 mg/m2 on days -4, -3 and -2 (total dose 90 mg/m2), followed by a singe dose of 2 Gy TBI administered on day 0, at a low dose-rate (≈ 7 cGy/min), before infusion of cells.
Conditioning regimen TBI + Fludarabine: 2 Gy TBI, Fludarabine 90 mg/m²
|
TLI-ATG
n=45 Participants
Conditioning consisting of 8 Gy TLI and ATG. TLI will be administered by linear accelerator at a dose of 80 cGy daily, starting 11 days before transplantation, until a total of 10 doses (800 cGy) has been delivered. The irradiation will consist of a supradiaphragmatic mantle field, a subdiaphragmatic field including an inverted Y and splenic ports, encompassing all major lymphoid organs, including the thymus, spleen, and lymph nodes, as used in the treatment of Hodgkin's disease (Kaplan HS, Cancer Research 26:1268-1276, 1966). The Waldeyer ring is not included. ATG (Thymoglobulin®, Genzyme), at a dose of 1.5 mg/kg/d, will be given intravenously on days -11 through -7.
Conditioning regimen II (TLI 8 Gy + ATG \[Thymoglobulin\]): TLI 8 Gy + ATG (Thymoglobulin) 7.5 mg/kg
|
Total
n=94 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
36 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
71 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
13 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Age, Continuous
|
60 years
n=5 Participants
|
59 years
n=7 Participants
|
60 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
35 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
64 Participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
45 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
88 Participants
n=5 Participants
|
|
Donor: HLA-identical sibling/ 10/10 HLA-allele matched URD
HLA-identical sibling
|
29 participants
n=5 Participants
|
25 participants
n=7 Participants
|
54 participants
n=5 Participants
|
|
Donor: HLA-identical sibling/ 10/10 HLA-allele matched URD
10/10 HLA-allele matched URD
|
20 participants
n=5 Participants
|
20 participants
n=7 Participants
|
40 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 180 days after HCTPopulation: Patients given a second allogeneic HCT were censured for GVHD analyses.
Percentage of participants with aGVHD according grades: Grade I: rash skin \< 25 % area; bilirubin: 20-30 mg/ml; diarrhea: 500-1000 ml/day Grade II: rash skin 25-50 % area; bilirubin: 30-60 mg/ml; diarrhea: 10000-1500 ml/day Grade III:rash skin \> 50 % area; bilirubin: 60-150 mg/ml; diarrhea: \>1500 ml/day Grade IV: erythroderma; bilirubin: \> 150 mg/ml; diarrhea: \>2000 ml/day Grade IV is the worst grade Patients given a second allogeneic HCT were censured for GVHD analyses.
Outcome measures
| Measure |
Flu-TBI
n=48 Participants
Conditioning regimen consisting of fludarabine 30 mg/m2 on days -4, -3 and -2 (total dose 90 mg/m2), followed by a singe dose of 2 Gy TBI administered on day 0, at a low dose-rate (≈ 7 cGy/min), before infusion of cells.
Conditioning regimen TBI + Fludarabine: 2 Gy TBI, Fludarabine 90 mg/m²
|
TLI-ATG
n=40 Participants
Conditioning consisting of 8 Gy TLI and ATG. TLI will be administered by linear accelerator at a dose of 80 cGy daily, starting 11 days before transplantation, until a total of 10 doses (800 cGy) has been delivered. The irradiation will consist of a supradiaphragmatic mantle field, a subdiaphragmatic field including an inverted Y and splenic ports, encompassing all major lymphoid organs, including the thymus, spleen, and lymph nodes, as used in the treatment of Hodgkin's disease (Kaplan HS, Cancer Research 26:1268-1276, 1966). The Waldeyer ring is not included. ATG (Thymoglobulin®, Genzyme), at a dose of 1.5 mg/kg/d, will be given intravenously on days -11 through -7.
Conditioning regimen II (TLI 8 Gy + ATG \[Thymoglobulin\]): TLI 8 Gy + ATG (Thymoglobulin) 7.5 mg/kg
|
|---|---|---|
|
Percentage of Participants With Grade II-IV Acute GVHD Between the 2 Groups
|
12.2 percentage of participants with aGVHD
|
8.9 percentage of participants with aGVHD
|
SECONDARY outcome
Timeframe: 1 year after HCTgraft rejection are reported in outcome measure data table (defined as ≤ 5% donor chimerism in T cells, total white blood cells and/or total bone marrow cells).
Outcome measures
| Measure |
Flu-TBI
n=49 Participants
Conditioning regimen consisting of fludarabine 30 mg/m2 on days -4, -3 and -2 (total dose 90 mg/m2), followed by a singe dose of 2 Gy TBI administered on day 0, at a low dose-rate (≈ 7 cGy/min), before infusion of cells.
Conditioning regimen TBI + Fludarabine: 2 Gy TBI, Fludarabine 90 mg/m²
|
TLI-ATG
n=45 Participants
Conditioning consisting of 8 Gy TLI and ATG. TLI will be administered by linear accelerator at a dose of 80 cGy daily, starting 11 days before transplantation, until a total of 10 doses (800 cGy) has been delivered. The irradiation will consist of a supradiaphragmatic mantle field, a subdiaphragmatic field including an inverted Y and splenic ports, encompassing all major lymphoid organs, including the thymus, spleen, and lymph nodes, as used in the treatment of Hodgkin's disease (Kaplan HS, Cancer Research 26:1268-1276, 1966). The Waldeyer ring is not included. ATG (Thymoglobulin®, Genzyme), at a dose of 1.5 mg/kg/d, will be given intravenously on days -11 through -7.
Conditioning regimen II (TLI 8 Gy + ATG \[Thymoglobulin\]): TLI 8 Gy + ATG (Thymoglobulin) 7.5 mg/kg
|
|---|---|---|
|
Number of Participants With Graft Rejection as Defined by Whole Blood and T Cell Chimerism
|
3 participants
|
4 participants
|
SECONDARY outcome
Timeframe: 2 years after HCTPopulation: Patients given a second allogeneic HCT were censured for GVHD analyses.
Comparaison of the number of Participants with chronic GVHD in the 2 groups
Outcome measures
| Measure |
Flu-TBI
n=48 Participants
Conditioning regimen consisting of fludarabine 30 mg/m2 on days -4, -3 and -2 (total dose 90 mg/m2), followed by a singe dose of 2 Gy TBI administered on day 0, at a low dose-rate (≈ 7 cGy/min), before infusion of cells.
Conditioning regimen TBI + Fludarabine: 2 Gy TBI, Fludarabine 90 mg/m²
|
TLI-ATG
n=40 Participants
Conditioning consisting of 8 Gy TLI and ATG. TLI will be administered by linear accelerator at a dose of 80 cGy daily, starting 11 days before transplantation, until a total of 10 doses (800 cGy) has been delivered. The irradiation will consist of a supradiaphragmatic mantle field, a subdiaphragmatic field including an inverted Y and splenic ports, encompassing all major lymphoid organs, including the thymus, spleen, and lymph nodes, as used in the treatment of Hodgkin's disease (Kaplan HS, Cancer Research 26:1268-1276, 1966). The Waldeyer ring is not included. ATG (Thymoglobulin®, Genzyme), at a dose of 1.5 mg/kg/d, will be given intravenously on days -11 through -7.
Conditioning regimen II (TLI 8 Gy + ATG \[Thymoglobulin\]): TLI 8 Gy + ATG (Thymoglobulin) 7.5 mg/kg
|
|---|---|---|
|
Percentage of Participants With Chronic GVHD in the 2 Groups
|
40.8 percentage of participants
|
18.8 percentage of participants
|
SECONDARY outcome
Timeframe: D100 after HCTOutcome measures
| Measure |
Flu-TBI
n=49 Participants
Conditioning regimen consisting of fludarabine 30 mg/m2 on days -4, -3 and -2 (total dose 90 mg/m2), followed by a singe dose of 2 Gy TBI administered on day 0, at a low dose-rate (≈ 7 cGy/min), before infusion of cells.
Conditioning regimen TBI + Fludarabine: 2 Gy TBI, Fludarabine 90 mg/m²
|
TLI-ATG
n=45 Participants
Conditioning consisting of 8 Gy TLI and ATG. TLI will be administered by linear accelerator at a dose of 80 cGy daily, starting 11 days before transplantation, until a total of 10 doses (800 cGy) has been delivered. The irradiation will consist of a supradiaphragmatic mantle field, a subdiaphragmatic field including an inverted Y and splenic ports, encompassing all major lymphoid organs, including the thymus, spleen, and lymph nodes, as used in the treatment of Hodgkin's disease (Kaplan HS, Cancer Research 26:1268-1276, 1966). The Waldeyer ring is not included. ATG (Thymoglobulin®, Genzyme), at a dose of 1.5 mg/kg/d, will be given intravenously on days -11 through -7.
Conditioning regimen II (TLI 8 Gy + ATG \[Thymoglobulin\]): TLI 8 Gy + ATG (Thymoglobulin) 7.5 mg/kg
|
|---|---|---|
|
Incidences of Bacterial, Fungal and Viral Infections in the 2 Groups.
Bacterial infection
|
19 participants
|
25 participants
|
|
Incidences of Bacterial, Fungal and Viral Infections in the 2 Groups.
Fungal infection
|
3 participants
|
7 participants
|
|
Incidences of Bacterial, Fungal and Viral Infections in the 2 Groups.
CMV reactivation
|
15 participants
|
21 participants
|
SECONDARY outcome
Timeframe: 1 year after HCTOutcome measures
| Measure |
Flu-TBI
n=49 Participants
Conditioning regimen consisting of fludarabine 30 mg/m2 on days -4, -3 and -2 (total dose 90 mg/m2), followed by a singe dose of 2 Gy TBI administered on day 0, at a low dose-rate (≈ 7 cGy/min), before infusion of cells.
Conditioning regimen TBI + Fludarabine: 2 Gy TBI, Fludarabine 90 mg/m²
|
TLI-ATG
n=45 Participants
Conditioning consisting of 8 Gy TLI and ATG. TLI will be administered by linear accelerator at a dose of 80 cGy daily, starting 11 days before transplantation, until a total of 10 doses (800 cGy) has been delivered. The irradiation will consist of a supradiaphragmatic mantle field, a subdiaphragmatic field including an inverted Y and splenic ports, encompassing all major lymphoid organs, including the thymus, spleen, and lymph nodes, as used in the treatment of Hodgkin's disease (Kaplan HS, Cancer Research 26:1268-1276, 1966). The Waldeyer ring is not included. ATG (Thymoglobulin®, Genzyme), at a dose of 1.5 mg/kg/d, will be given intravenously on days -11 through -7.
Conditioning regimen II (TLI 8 Gy + ATG \[Thymoglobulin\]): TLI 8 Gy + ATG (Thymoglobulin) 7.5 mg/kg
|
|---|---|---|
|
Percentage of Relapse Rate in the 2 Groups
|
22 percentage of Relapse
|
50 percentage of Relapse
|
SECONDARY outcome
Timeframe: Day 0, Day 3 and Day 10Analyses of ATG levels in order to assess the immune system recuperation
Outcome measures
| Measure |
Flu-TBI
n=15 Participants
Conditioning regimen consisting of fludarabine 30 mg/m2 on days -4, -3 and -2 (total dose 90 mg/m2), followed by a singe dose of 2 Gy TBI administered on day 0, at a low dose-rate (≈ 7 cGy/min), before infusion of cells.
Conditioning regimen TBI + Fludarabine: 2 Gy TBI, Fludarabine 90 mg/m²
|
TLI-ATG
Conditioning consisting of 8 Gy TLI and ATG. TLI will be administered by linear accelerator at a dose of 80 cGy daily, starting 11 days before transplantation, until a total of 10 doses (800 cGy) has been delivered. The irradiation will consist of a supradiaphragmatic mantle field, a subdiaphragmatic field including an inverted Y and splenic ports, encompassing all major lymphoid organs, including the thymus, spleen, and lymph nodes, as used in the treatment of Hodgkin's disease (Kaplan HS, Cancer Research 26:1268-1276, 1966). The Waldeyer ring is not included. ATG (Thymoglobulin®, Genzyme), at a dose of 1.5 mg/kg/d, will be given intravenously on days -11 through -7.
Conditioning regimen II (TLI 8 Gy + ATG \[Thymoglobulin\]): TLI 8 Gy + ATG (Thymoglobulin) 7.5 mg/kg
|
|---|---|---|
|
Quality and Timing of Immunologic Reconstitution: Concentration of ATG Levels
Median ATG serum levels at day 0
|
4 mg/L
Interval 3.8 to 4.2
|
—
|
|
Quality and Timing of Immunologic Reconstitution: Concentration of ATG Levels
Median ATG serum levels at day 3
|
2.2 mg/L
Interval 2.09 to 2.31
|
—
|
|
Quality and Timing of Immunologic Reconstitution: Concentration of ATG Levels
Median ATG serum levels at day 10
|
0.95 mg/L
Interval 0.9025 to 0.9975
|
—
|
SECONDARY outcome
Timeframe: 1 year after HCTOutcome measures
| Measure |
Flu-TBI
n=49 Participants
Conditioning regimen consisting of fludarabine 30 mg/m2 on days -4, -3 and -2 (total dose 90 mg/m2), followed by a singe dose of 2 Gy TBI administered on day 0, at a low dose-rate (≈ 7 cGy/min), before infusion of cells.
Conditioning regimen TBI + Fludarabine: 2 Gy TBI, Fludarabine 90 mg/m²
|
TLI-ATG
n=45 Participants
Conditioning consisting of 8 Gy TLI and ATG. TLI will be administered by linear accelerator at a dose of 80 cGy daily, starting 11 days before transplantation, until a total of 10 doses (800 cGy) has been delivered. The irradiation will consist of a supradiaphragmatic mantle field, a subdiaphragmatic field including an inverted Y and splenic ports, encompassing all major lymphoid organs, including the thymus, spleen, and lymph nodes, as used in the treatment of Hodgkin's disease (Kaplan HS, Cancer Research 26:1268-1276, 1966). The Waldeyer ring is not included. ATG (Thymoglobulin®, Genzyme), at a dose of 1.5 mg/kg/d, will be given intravenously on days -11 through -7.
Conditioning regimen II (TLI 8 Gy + ATG \[Thymoglobulin\]): TLI 8 Gy + ATG (Thymoglobulin) 7.5 mg/kg
|
|---|---|---|
|
Percentage of Non Relapse Mortality in the 2 Groups
|
24 percentage of participants
|
13 percentage of participants
|
SECONDARY outcome
Timeframe: 4 year after HCTOutcome measures
| Measure |
Flu-TBI
n=49 Participants
Conditioning regimen consisting of fludarabine 30 mg/m2 on days -4, -3 and -2 (total dose 90 mg/m2), followed by a singe dose of 2 Gy TBI administered on day 0, at a low dose-rate (≈ 7 cGy/min), before infusion of cells.
Conditioning regimen TBI + Fludarabine: 2 Gy TBI, Fludarabine 90 mg/m²
|
TLI-ATG
n=45 Participants
Conditioning consisting of 8 Gy TLI and ATG. TLI will be administered by linear accelerator at a dose of 80 cGy daily, starting 11 days before transplantation, until a total of 10 doses (800 cGy) has been delivered. The irradiation will consist of a supradiaphragmatic mantle field, a subdiaphragmatic field including an inverted Y and splenic ports, encompassing all major lymphoid organs, including the thymus, spleen, and lymph nodes, as used in the treatment of Hodgkin's disease (Kaplan HS, Cancer Research 26:1268-1276, 1966). The Waldeyer ring is not included. ATG (Thymoglobulin®, Genzyme), at a dose of 1.5 mg/kg/d, will be given intravenously on days -11 through -7.
Conditioning regimen II (TLI 8 Gy + ATG \[Thymoglobulin\]): TLI 8 Gy + ATG (Thymoglobulin) 7.5 mg/kg
|
|---|---|---|
|
Percentage of 4-year Progression Free Survival in the 2 Groups
|
54 percentage of participants
|
37 percentage of participants
|
SECONDARY outcome
Timeframe: 5 year after HCTOutcome measures
| Measure |
Flu-TBI
n=49 Participants
Conditioning regimen consisting of fludarabine 30 mg/m2 on days -4, -3 and -2 (total dose 90 mg/m2), followed by a singe dose of 2 Gy TBI administered on day 0, at a low dose-rate (≈ 7 cGy/min), before infusion of cells.
Conditioning regimen TBI + Fludarabine: 2 Gy TBI, Fludarabine 90 mg/m²
|
TLI-ATG
n=45 Participants
Conditioning consisting of 8 Gy TLI and ATG. TLI will be administered by linear accelerator at a dose of 80 cGy daily, starting 11 days before transplantation, until a total of 10 doses (800 cGy) has been delivered. The irradiation will consist of a supradiaphragmatic mantle field, a subdiaphragmatic field including an inverted Y and splenic ports, encompassing all major lymphoid organs, including the thymus, spleen, and lymph nodes, as used in the treatment of Hodgkin's disease (Kaplan HS, Cancer Research 26:1268-1276, 1966). The Waldeyer ring is not included. ATG (Thymoglobulin®, Genzyme), at a dose of 1.5 mg/kg/d, will be given intravenously on days -11 through -7.
Conditioning regimen II (TLI 8 Gy + ATG \[Thymoglobulin\]): TLI 8 Gy + ATG (Thymoglobulin) 7.5 mg/kg
|
|---|---|---|
|
Percentage of 5-year Progression Free Survival in the 2 Groups
|
50 percentage of participants
|
37 percentage of participants
|
SECONDARY outcome
Timeframe: 4 year after HCTOutcome measures
| Measure |
Flu-TBI
n=49 Participants
Conditioning regimen consisting of fludarabine 30 mg/m2 on days -4, -3 and -2 (total dose 90 mg/m2), followed by a singe dose of 2 Gy TBI administered on day 0, at a low dose-rate (≈ 7 cGy/min), before infusion of cells.
Conditioning regimen TBI + Fludarabine: 2 Gy TBI, Fludarabine 90 mg/m²
|
TLI-ATG
n=45 Participants
Conditioning consisting of 8 Gy TLI and ATG. TLI will be administered by linear accelerator at a dose of 80 cGy daily, starting 11 days before transplantation, until a total of 10 doses (800 cGy) has been delivered. The irradiation will consist of a supradiaphragmatic mantle field, a subdiaphragmatic field including an inverted Y and splenic ports, encompassing all major lymphoid organs, including the thymus, spleen, and lymph nodes, as used in the treatment of Hodgkin's disease (Kaplan HS, Cancer Research 26:1268-1276, 1966). The Waldeyer ring is not included. ATG (Thymoglobulin®, Genzyme), at a dose of 1.5 mg/kg/d, will be given intravenously on days -11 through -7.
Conditioning regimen II (TLI 8 Gy + ATG \[Thymoglobulin\]): TLI 8 Gy + ATG (Thymoglobulin) 7.5 mg/kg
|
|---|---|---|
|
Percentage of 4-year Overall Survival in the 2 Groups
|
53 percentage of participants
|
54 percentage of participants
|
SECONDARY outcome
Timeframe: 5 year after HCTOutcome measures
| Measure |
Flu-TBI
n=49 Participants
Conditioning regimen consisting of fludarabine 30 mg/m2 on days -4, -3 and -2 (total dose 90 mg/m2), followed by a singe dose of 2 Gy TBI administered on day 0, at a low dose-rate (≈ 7 cGy/min), before infusion of cells.
Conditioning regimen TBI + Fludarabine: 2 Gy TBI, Fludarabine 90 mg/m²
|
TLI-ATG
n=45 Participants
Conditioning consisting of 8 Gy TLI and ATG. TLI will be administered by linear accelerator at a dose of 80 cGy daily, starting 11 days before transplantation, until a total of 10 doses (800 cGy) has been delivered. The irradiation will consist of a supradiaphragmatic mantle field, a subdiaphragmatic field including an inverted Y and splenic ports, encompassing all major lymphoid organs, including the thymus, spleen, and lymph nodes, as used in the treatment of Hodgkin's disease (Kaplan HS, Cancer Research 26:1268-1276, 1966). The Waldeyer ring is not included. ATG (Thymoglobulin®, Genzyme), at a dose of 1.5 mg/kg/d, will be given intravenously on days -11 through -7.
Conditioning regimen II (TLI 8 Gy + ATG \[Thymoglobulin\]): TLI 8 Gy + ATG (Thymoglobulin) 7.5 mg/kg
|
|---|---|---|
|
Percentage of 5-year Overall Survival in the 2 Groups
|
53 percentage of participants
|
55 percentage of participants
|
Adverse Events
Flu-TBI
Serious events: 41 serious events
Other events: 15 other events
Deaths: 22 deaths
TLI-ATG
Serious events: 41 serious events
Other events: 21 other events
Deaths: 19 deaths
Serious adverse events
| Measure |
Flu-TBI
n=49 participants at risk
Conditioning regimen consisting of fludarabine 30 mg/m2 on days -4, -3 and -2 (total dose 90 mg/m2), followed by a singe dose of 2 Gy TBI administered on day 0, at a low dose-rate (≈ 7 cGy/min), before infusion of cells.
Conditioning regimen TBI + Fludarabine: 2 Gy TBI, Fludarabine 90 mg/m²
|
TLI-ATG
n=45 participants at risk
Conditioning consisting of 8 Gy TLI and ATG. TLI will be administered by linear accelerator at a dose of 80 cGy daily, starting 11 days before transplantation, until a total of 10 doses (800 cGy) has been delivered. The irradiation will consist of a supradiaphragmatic mantle field, a subdiaphragmatic field including an inverted Y and splenic ports, encompassing all major lymphoid organs, including the thymus, spleen, and lymph nodes, as used in the treatment of Hodgkin's disease (Kaplan HS, Cancer Research 26:1268-1276, 1966). The Waldeyer ring is not included. ATG (Thymoglobulin®, Genzyme), at a dose of 1.5 mg/kg/d, will be given intravenously on days -11 through -7.
Conditioning regimen II (TLI 8 Gy + ATG \[Thymoglobulin\]): TLI 8 Gy + ATG (Thymoglobulin) 7.5 mg/kg
|
|---|---|---|
|
Immune system disorders
acute Graft versus Host Disease
|
10.2%
5/49 • 5 years
|
11.1%
5/45 • 5 years
|
|
Immune system disorders
chronic Graft versus Host Disease
|
40.8%
20/49 • 5 years
|
28.9%
13/45 • 5 years
|
|
Blood and lymphatic system disorders
Graft failure
|
6.1%
3/49 • 5 years
|
8.9%
4/45 • 5 years
|
|
Blood and lymphatic system disorders
Relapse/progression
|
24.5%
12/49 • 5 years
|
48.9%
22/45 • 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrom
|
2.0%
1/49 • 5 years
|
0.00%
0/45 • 5 years
|
|
Infections and infestations
Lung
|
14.3%
7/49 • 5 years
|
4.4%
2/45 • 5 years
|
|
Infections and infestations
Septic shock
|
10.2%
5/49 • 5 years
|
11.1%
5/45 • 5 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Second maligancy
|
2.0%
1/49 • 5 years
|
2.2%
1/45 • 5 years
|
|
Infections and infestations
Viral infection
|
12.2%
6/49 • 5 years
|
8.9%
4/45 • 5 years
|
|
General disorders
Fever unknown origin
|
6.1%
3/49 • 5 years
|
11.1%
5/45 • 5 years
|
|
General disorders
Multiple organ failure
|
0.00%
0/49 • 5 years
|
2.2%
1/45 • 5 years
|
|
Surgical and medical procedures
surgical procedure
|
4.1%
2/49 • 5 years
|
6.7%
3/45 • 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
4.1%
2/49 • 5 years
|
0.00%
0/45 • 5 years
|
|
Infections and infestations
Catheter
|
4.1%
2/49 • 5 years
|
0.00%
0/45 • 5 years
|
|
Infections and infestations
Urinary tract
|
4.1%
2/49 • 5 years
|
0.00%
0/45 • 5 years
|
|
Gastrointestinal disorders
GI complains
|
8.2%
4/49 • 5 years
|
6.7%
3/45 • 5 years
|
|
Nervous system disorders
Neurologic troubles
|
8.2%
4/49 • 5 years
|
2.2%
1/45 • 5 years
|
|
Nervous system disorders
Epilepsy
|
2.0%
1/49 • 5 years
|
0.00%
0/45 • 5 years
|
|
Blood and lymphatic system disorders
Hemolytic anemia
|
0.00%
0/49 • 5 years
|
2.2%
1/45 • 5 years
|
|
Blood and lymphatic system disorders
Alveolar Hemorrhage
|
2.0%
1/49 • 5 years
|
2.2%
1/45 • 5 years
|
|
Blood and lymphatic system disorders
Hematuria
|
0.00%
0/49 • 5 years
|
2.2%
1/45 • 5 years
|
|
Renal and urinary disorders
Acute renal failure
|
0.00%
0/49 • 5 years
|
4.4%
2/45 • 5 years
|
Other adverse events
| Measure |
Flu-TBI
n=49 participants at risk
Conditioning regimen consisting of fludarabine 30 mg/m2 on days -4, -3 and -2 (total dose 90 mg/m2), followed by a singe dose of 2 Gy TBI administered on day 0, at a low dose-rate (≈ 7 cGy/min), before infusion of cells.
Conditioning regimen TBI + Fludarabine: 2 Gy TBI, Fludarabine 90 mg/m²
|
TLI-ATG
n=45 participants at risk
Conditioning consisting of 8 Gy TLI and ATG. TLI will be administered by linear accelerator at a dose of 80 cGy daily, starting 11 days before transplantation, until a total of 10 doses (800 cGy) has been delivered. The irradiation will consist of a supradiaphragmatic mantle field, a subdiaphragmatic field including an inverted Y and splenic ports, encompassing all major lymphoid organs, including the thymus, spleen, and lymph nodes, as used in the treatment of Hodgkin's disease (Kaplan HS, Cancer Research 26:1268-1276, 1966). The Waldeyer ring is not included. ATG (Thymoglobulin®, Genzyme), at a dose of 1.5 mg/kg/d, will be given intravenously on days -11 through -7.
Conditioning regimen II (TLI 8 Gy + ATG \[Thymoglobulin\]): TLI 8 Gy + ATG (Thymoglobulin) 7.5 mg/kg
|
|---|---|---|
|
Infections and infestations
CMV reactivation
|
30.6%
15/49 • 5 years
|
46.7%
21/45 • 5 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place