Trial Outcomes & Findings for Allogeneic Transplantation Using Total Lymphoid Irradiation (TLI) and Anti-Thymocyte Globulin (ATG) for Older Patients With Hematologic Malignancies (NCT NCT00185640)

Last Updated: 2021-06-29

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

303 participants

Primary outcome timeframe

100 days post-transplant

Results posted on

2021-06-29

Participant Flow

Participant milestones

Participant milestones
Measure	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
Overall Study STARTED	303
Overall Study Transplanted	296
Overall Study 90 Days Post-transplant	161
Overall Study COMPLETED	158
Overall Study NOT COMPLETED	145

Reasons for withdrawal

Reasons for withdrawal
Measure	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
Overall Study Not Eligible	4
Overall Study Withdrawal by Subject	3
Overall Study Death	138

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Non-myeloablative Transplantation n=303 Participants 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
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	260 Participants n=5 Participants
Age, Categorical >=65 years	43 Participants n=5 Participants
Sex: Female, Male Female	128 Participants n=5 Participants
Sex: Female, Male Male	175 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	276 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	37 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	7 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants
Race (NIH/OMB) White	233 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	20 Participants n=5 Participants
Histology Acute Biphenotypic Leukemia	1 participants n=5 Participants
Histology Acute Leukemia, Nos	1 participants n=5 Participants
Histology Acute Monocytic Leukemia	2 participants n=5 Participants
Histology Acute Myeloid Leukemia	84 participants n=5 Participants
Histology Acute Promyelocytic Leukemia	4 participants n=5 Participants
Histology Angioimmunoblastic T-Cell Lymphoma	1 participants n=5 Participants
Histology B lymphoblastic leukemia/lymphoma, NOS	1 participants n=5 Participants
Histology B-Cell Chr. Lymph. Leuk./Small Lymph. Lymphoma	45 participants n=5 Participants
Histology Chronic Myelogenous Leukemia, Bcr/Abl Positive	1 participants n=5 Participants
Histology Chronic Myeloid Leukemia, Nos	8 participants n=5 Participants
Histology Chronic Myeloproliferative Disease, Nos	2 participants n=5 Participants
Histology Cutaneous T-Cell Lymphoma, Nos	1 participants n=5 Participants
Histology Follicular Lymphoma, Grade 1-3	4 participants n=5 Participants
Histology Hodgkin Lymphoma, Nodular Sclerosis, Nos	4 participants n=5 Participants
Histology Hodgkin Lymphoma, Nos	20 participants n=5 Participants
Histology Malignant Lymphoma, Non-Hodgkin	86 participants n=5 Participants
Histology Mantle Cell Lymphoma	10 participants n=5 Participants
Histology Marginal Zone B-Cell Lymphoma, Nos	2 participants n=5 Participants
Histology Mature T-Cell Lymphoma, Nos	1 participants n=5 Participants
Histology Ml, Large B-Cell, Diffuse	2 participants n=5 Participants
Histology Ml, Small B Lymphocytic, Nos	1 participants n=5 Participants
Histology Myelodysplastic Syndrome, Nos	3 participants n=5 Participants
Histology Precursor Cell Lymphoblastic Leukemia, Nos	15 participants n=5 Participants
Histology Prolymphocytic Leukemia, Nos	1 participants n=5 Participants
Histology Prolymphocytic Leukemia, T-Cell Type	1 participants n=5 Participants
Histology Subcutaneous Panniculitis-Like T-Cell Lymphoma	1 participants n=5 Participants
Histology Unknown	1 participants n=5 Participants

PRIMARY outcome

Timeframe: 100 days post-transplant

Population: 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.

Outcome measures

Outcome measures
Measure	Non-myeloablative Transplantation n=37 Participants 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.
Acute Graft vs Host Disease (GvHD)	2.7 percentage of participants

SECONDARY outcome

Timeframe: 100 days post-transplant

Population: Reports data for all evaluable participants

Outcome measures

Outcome measures
Measure	Non-myeloablative Transplantation n=303 Participants 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.
Acute Graft vs Host Disease (GvHD), All Evaluable	11 percentage of participants

SECONDARY outcome

Timeframe: 3 years

Reports the overall rate of disease relapse, occurring any time within 3 years after transplant

Outcome measures

Outcome measures
Measure	Non-myeloablative Transplantation n=303 Participants 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.
Incidence of Relapse	53 percentage of participants

SECONDARY outcome

Timeframe: 3 and 5 years

Outcome measures

Outcome measures
Measure	Non-myeloablative Transplantation n=303 Participants 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 Survival (OS) 3 years	70 percentage of participants
Overall Survival (OS) 5 years	64 percentage of participants

SECONDARY outcome

Timeframe: 3 and 5 years

Reports the number and proportion of participants who neither died due to any cause nor experienced relapse.

Outcome measures

Outcome measures
Measure	Non-myeloablative Transplantation n=303 Participants 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.
Event-free Survival (EFS) 3 years	44 Participants
Event-free Survival (EFS) 5 years	38 Participants

SECONDARY outcome

Timeframe: 1 year

Reports the proportion of participants who expired within 1 year due to any complication or failure of the transplant.

Outcome measures

Outcome measures
Measure	Non-myeloablative Transplantation n=303 Participants 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.
Transplant-related Mortality	6 percentage of participants

Adverse Events

Non-myeloablative Transplantation

Serious events: 138 serious events

Other events: 55 other events

Deaths: 138 deaths

Serious adverse events

Serious adverse events
Measure	Non-myeloablative Transplantation n=303 participants at risk
Gastrointestinal disorders Deaths	45.5% 138/303 • 5 years Adverse events other than death, secondary malignancy, or relapse were not collected.

Other adverse events

Other adverse events
Measure	Non-myeloablative Transplantation n=303 participants at risk
Gastrointestinal disorders Secondary malignancy	1.3% 4/303 • Number of events 4 • 5 years Adverse events other than death, secondary malignancy, or relapse were not collected.
Skin and subcutaneous tissue disorders Secondary malignancy	8.6% 26/303 • Number of events 26 • 5 years Adverse events other than death, secondary malignancy, or relapse were not collected.
Reproductive system and breast disorders Secondary malignancy	0.66% 2/303 • Number of events 2 • 5 years Adverse events other than death, secondary malignancy, or relapse were not collected.
Respiratory, thoracic and mediastinal disorders Secondary malignancy	0.33% 1/303 • Number of events 1 • 5 years Adverse events other than death, secondary malignancy, or relapse were not collected.
Blood and lymphatic system disorders Secondary malignancy	7.3% 22/303 • Number of events 22 • 5 years Adverse events other than death, secondary malignancy, or relapse were not collected.

Additional Information

Robert Lowsky

Stanford University

Phone: 650-723-0822

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place