Trial Outcomes & Findings for Total Body Irradiation +/- Total Lymphoid Irradiation & Anti-Thymocyte Globulin in Non-myeloablative Hematopoietic Cell Transplantation (NCT NCT03734601)

Last Updated: 2023-12-12

Results Overview

Subsequent to TLI/ATG/TBI conditioning, the proportion of participants with full dose donor chimerism (FDC) will be determined by Day 28. FDC is defined as achieving ≥ 95% donor type in the CD3+ lineage within 28 days of donor cell infusion, as assessed by short tandem repeat (STR) testing. The outcome will be expressed as the number of participants that achieve FDC by Day 28, a number without dispersion.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

22 participants

Primary outcome timeframe

Day 28

Results posted on

2023-12-12

Participant Flow

Participant milestones

Participant milestones
Measure	TBI+TLI TBI, single exposure on Day -1, 80 centigray (cGy) in addition to total lymphoid irradiation (TLI, 120 cGy/day for 9 days, weekends excluded) and anti-thymocyte globulin (ATG) 1.5 mg/kg (conditioning regimen) Total body irradiation (TBI): Administer Total body irradiation (TBI) 80 cGy on Day 1 of standard TLI ATG conditioning Anti-thymocyte globulin (ATG): Given intravenous (IV), Dose 1.5 mg/kg x 5 days Tacrolimus: Oral, Dose 0.05 mg/kg twice daily, can be given intravenous (IV) Mycophenolate mofetil (MMF): Given Oral, 15 mg/k every 2 hours for peripheral blood stem cells (PBSC) from matched related donors; 15 mg/kg every 8 hours for PBSC from unrelated donors (URDs) or mismatched related donors. Total lymphoid irradiation (TLI): 9 x 120 cGy over 11 days
Overall Study STARTED	22
Overall Study COMPLETED	22
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Total Body Irradiation +/- Total Lymphoid Irradiation & Anti-Thymocyte Globulin in Non-myeloablative Hematopoietic Cell Transplantation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TBI+TLI n=22 Participants TBI, single exposure on Day -1, 80 centigray (cGy) in addition to total lymphoid irradiation (TLI, 120 cGy/day for 9 days, weekends excluded) and anti-thymocyte globulin (ATG) 1.5 mg/kg (conditioning regimen) Total body irradiation (TBI): Administer Total body irradiation (TBI) 80 cGy on Day 1 of standard TLI ATG conditioning Anti-thymocyte globulin (ATG): Given intravenous (IV), Dose 1.5 mg/kg x 5 days Tacrolimus: Oral, Dose 0.05 mg/kg twice daily, can be given intravenous (IV) Mycophenolate mofetil (MMF): Given Oral, 15 mg/k every 2 hours for peripheral blood stem cells (PBSC) from matched related donors; 15 mg/kg every 8 hours for PBSC from unrelated donors (URDs) or mismatched related donors. Total lymphoid irradiation (TLI): 9 x 120 cGy over 11 days
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants
Age, Categorical >=65 years	17 Participants n=5 Participants
Age, Continuous	67.2 years STANDARD_DEVIATION 10.8 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	15 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants
Region of Enrollment United States	22 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 28

Outcome measures

Outcome measures
Measure	TBI+TLI n=22 Participants TBI, single exposure on Day -1, 80 centigray (cGy) in addition to total lymphoid irradiation (TLI, 120 cGy/day for 9 days, weekends excluded) and anti-thymocyte globulin (ATG) 1.5 mg/kg (conditioning regimen) Total body irradiation (TBI): Administer Total body irradiation (TBI) 80 cGy on Day 1 of standard TLI ATG conditioning Anti-thymocyte globulin (ATG): Given intravenous (IV), Dose 1.5 mg/kg x 5 days Tacrolimus: Oral, Dose 0.05 mg/kg twice daily, can be given intravenous (IV) Mycophenolate mofetil (MMF): Given Oral, 15 mg/k every 2 hours for peripheral blood stem cells (PBSC) from matched related donors; 15 mg/kg every 8 hours for PBSC from unrelated donors (URDs) or mismatched related donors. Total lymphoid irradiation (TLI): 9 x 120 cGy over 11 days
Full-dose Donor Chimerism (FDC) at Day 28 Following TLI/ATG/TBI Conditioning.	13 Participants

SECONDARY outcome

Timeframe: 1 year

Transplant recipients will be assessed for disease progression at 1 year after hematopoietic cell transplantation (HCT). The outcome is reported as the number of transplant recipients who experienced disease progression.

Outcome measures

Outcome measures
Measure	TBI+TLI n=22 Participants TBI, single exposure on Day -1, 80 centigray (cGy) in addition to total lymphoid irradiation (TLI, 120 cGy/day for 9 days, weekends excluded) and anti-thymocyte globulin (ATG) 1.5 mg/kg (conditioning regimen) Total body irradiation (TBI): Administer Total body irradiation (TBI) 80 cGy on Day 1 of standard TLI ATG conditioning Anti-thymocyte globulin (ATG): Given intravenous (IV), Dose 1.5 mg/kg x 5 days Tacrolimus: Oral, Dose 0.05 mg/kg twice daily, can be given intravenous (IV) Mycophenolate mofetil (MMF): Given Oral, 15 mg/k every 2 hours for peripheral blood stem cells (PBSC) from matched related donors; 15 mg/kg every 8 hours for PBSC from unrelated donors (URDs) or mismatched related donors. Total lymphoid irradiation (TLI): 9 x 120 cGy over 11 days
Disease Progression	7 Participants

SECONDARY outcome

Timeframe: 1 year

Overall survival (OS) is defined as the number of transplant recipients remaining alive at 12 months after transplant. The outcome is expressed as the number of transplant recipients who remained alive at 12 months after treatment, a number without dispersion.

Outcome measures

Outcome measures
Measure	TBI+TLI n=22 Participants TBI, single exposure on Day -1, 80 centigray (cGy) in addition to total lymphoid irradiation (TLI, 120 cGy/day for 9 days, weekends excluded) and anti-thymocyte globulin (ATG) 1.5 mg/kg (conditioning regimen) Total body irradiation (TBI): Administer Total body irradiation (TBI) 80 cGy on Day 1 of standard TLI ATG conditioning Anti-thymocyte globulin (ATG): Given intravenous (IV), Dose 1.5 mg/kg x 5 days Tacrolimus: Oral, Dose 0.05 mg/kg twice daily, can be given intravenous (IV) Mycophenolate mofetil (MMF): Given Oral, 15 mg/k every 2 hours for peripheral blood stem cells (PBSC) from matched related donors; 15 mg/kg every 8 hours for PBSC from unrelated donors (URDs) or mismatched related donors. Total lymphoid irradiation (TLI): 9 x 120 cGy over 11 days
Overall Survival (OS)	16 Participants

SECONDARY outcome

Timeframe: 1 year

Event-free survival (EFS) is defined as the number of transplant recipients remaining alive at 12 months after transplant and who did not experience disease relapse defined as blasts \< 5%. The outcome is expressed as the number of transplant recipients remaining alive at 12 months after transplant without disease relapse, a number without dispersion.

Outcome measures

Outcome measures
Measure	TBI+TLI n=22 Participants TBI, single exposure on Day -1, 80 centigray (cGy) in addition to total lymphoid irradiation (TLI, 120 cGy/day for 9 days, weekends excluded) and anti-thymocyte globulin (ATG) 1.5 mg/kg (conditioning regimen) Total body irradiation (TBI): Administer Total body irradiation (TBI) 80 cGy on Day 1 of standard TLI ATG conditioning Anti-thymocyte globulin (ATG): Given intravenous (IV), Dose 1.5 mg/kg x 5 days Tacrolimus: Oral, Dose 0.05 mg/kg twice daily, can be given intravenous (IV) Mycophenolate mofetil (MMF): Given Oral, 15 mg/k every 2 hours for peripheral blood stem cells (PBSC) from matched related donors; 15 mg/kg every 8 hours for PBSC from unrelated donors (URDs) or mismatched related donors. Total lymphoid irradiation (TLI): 9 x 120 cGy over 11 days
Event-free Survival (EFS) at 1 Year	16 Participants

SECONDARY outcome

Timeframe: 1 year

Non-relapse mortality (NRM) is defined as death without known disease relapse or recurrence. The outcome is expressed as the number of transplant recipients whose cause of death was not disease relapse or recurrence, a number without dispersion.

Outcome measures

Outcome measures
Measure	TBI+TLI n=22 Participants TBI, single exposure on Day -1, 80 centigray (cGy) in addition to total lymphoid irradiation (TLI, 120 cGy/day for 9 days, weekends excluded) and anti-thymocyte globulin (ATG) 1.5 mg/kg (conditioning regimen) Total body irradiation (TBI): Administer Total body irradiation (TBI) 80 cGy on Day 1 of standard TLI ATG conditioning Anti-thymocyte globulin (ATG): Given intravenous (IV), Dose 1.5 mg/kg x 5 days Tacrolimus: Oral, Dose 0.05 mg/kg twice daily, can be given intravenous (IV) Mycophenolate mofetil (MMF): Given Oral, 15 mg/k every 2 hours for peripheral blood stem cells (PBSC) from matched related donors; 15 mg/kg every 8 hours for PBSC from unrelated donors (URDs) or mismatched related donors. Total lymphoid irradiation (TLI): 9 x 120 cGy over 11 days
Non-relapse Mortality (NRM)	2 Participants

SECONDARY outcome

Timeframe: 1 year

Population: Per protocol, the outcome for chronic extensive and persistent GvHD is based on the subset of participants that had chronic and extensive GvHD.

Recipients will be monitored for Grade 2 to 4 graft vs host disease (GvHD). The outcome is reported as the number of transplant recipients who experienced acute GvHD grades 2 to 4, the number of transplant recipients who experienced chronic and extensive GvHD. In addition, the number of transplant recipients with chronic and extensive GvHD that was refractory to treatment ("persistent") is reported. Per protocol, the result for chronic extensive and persistent GvHD is based on the subset of participants that had chronic and extensive GvHD.

Outcome measures

Outcome measures
Measure	TBI+TLI n=22 Participants TBI, single exposure on Day -1, 80 centigray (cGy) in addition to total lymphoid irradiation (TLI, 120 cGy/day for 9 days, weekends excluded) and anti-thymocyte globulin (ATG) 1.5 mg/kg (conditioning regimen) Total body irradiation (TBI): Administer Total body irradiation (TBI) 80 cGy on Day 1 of standard TLI ATG conditioning Anti-thymocyte globulin (ATG): Given intravenous (IV), Dose 1.5 mg/kg x 5 days Tacrolimus: Oral, Dose 0.05 mg/kg twice daily, can be given intravenous (IV) Mycophenolate mofetil (MMF): Given Oral, 15 mg/k every 2 hours for peripheral blood stem cells (PBSC) from matched related donors; 15 mg/kg every 8 hours for PBSC from unrelated donors (URDs) or mismatched related donors. Total lymphoid irradiation (TLI): 9 x 120 cGy over 11 days
Graft vs Host Disease (GvHD) Chronic extensive GvHD	8 Participants
Graft vs Host Disease (GvHD) Acute GvHD	5 Participants
Graft vs Host Disease (GvHD) Chronic extensive and persistent GvHD	3 Participants

Adverse Events

TBI+TLI

Serious events: 2 serious events

Other events: 0 other events

Deaths: 6 deaths

Serious adverse events

Serious adverse events
Measure	TBI+TLI n=22 participants at risk TBI, single exposure on Day -1, 80 centigray (cGy) in addition to total lymphoid irradiation (TLI, 120 cGy/day for 9 days, weekends excluded) and anti-thymocyte globulin (ATG) 1.5 mg/kg (conditioning regimen) Total body irradiation (TBI): Administer Total body irradiation (TBI) 80 cGy on Day 1 of standard TLI ATG conditioning Anti-thymocyte globulin (ATG): Given intravenous (IV), Dose 1.5 mg/kg x 5 days Tacrolimus: Oral, Dose 0.05 mg/kg twice daily, can be given intravenous (IV) Mycophenolate mofetil (MMF): Given Oral, 15 mg/k every 2 hours for peripheral blood stem cells (PBSC) from matched related donors; 15 mg/kg every 8 hours for PBSC from unrelated donors (URDs) or mismatched related donors. Total lymphoid irradiation (TLI): 9 x 120 cGy over 11 days
Blood and lymphatic system disorders Febrile neutropenia	4.5% 1/22 • Number of events 1 • 60 days, except collection of mortality information was open-ended. Per protocol, adverse event collection was limited, as follows. * Non-serious adverse event collection was limited to Grade 1 to 3 events that resulted in participant termination or withdrawal from the study * Serious adverse events, and details of, were only collected for 60 days after the transplant. * Mortality collection was open-ended.
Immune system disorders Chronic graft vs host disease	4.5% 1/22 • Number of events 1 • 60 days, except collection of mortality information was open-ended. Per protocol, adverse event collection was limited, as follows. * Non-serious adverse event collection was limited to Grade 1 to 3 events that resulted in participant termination or withdrawal from the study * Serious adverse events, and details of, were only collected for 60 days after the transplant. * Mortality collection was open-ended.
Infections and infestations Sepsis	4.5% 1/22 • Number of events 1 • 60 days, except collection of mortality information was open-ended. Per protocol, adverse event collection was limited, as follows. * Non-serious adverse event collection was limited to Grade 1 to 3 events that resulted in participant termination or withdrawal from the study * Serious adverse events, and details of, were only collected for 60 days after the transplant. * Mortality collection was open-ended.

Other adverse events

Adverse event data not reported

Additional Information

Robert Lowsky, Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

Stanford University

Phone: 650-723-0822

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place