Trial Outcomes & Findings for Phase 2 Poor Risk DLBCL of TLI and ATG Followed by Matched Allogeneic HT as Consolidation to Autologous HCT (NCT NCT00482053)

NCT ID: NCT00482053

Last Updated: 2018-05-14

Results Overview

Event-free survival (EFS) through 4 years, as assessed in participants with poor-risk recurrent or primary refractory DLBCL treated with TLI and ATG followed by matched allogeneic hematopoietic cell transplantation as a consolidation to HCT. Event is defined as tumor progression or death.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

3 participants

Primary outcome timeframe

48 months

Results posted on

2018-05-14

Participant Flow

Participant milestones

Participant milestones
Measure	Auto-HCT Followed by Allo-HCT for Poor-risk DLBCL Participants will have peripheral blood stem cells (PBSC, aka progenitor / stem cells) mobilized to peripheral blood with rituximab, chemotherapy (cyclophosphamide or etoposide), and filgrastim; undergo apheresis to collect (self/autologous PBSC), and receive carmustine, etoposide, and cyclophosphamide as conditioning for PBSC infusion as a hematopoietic cell transplant (auto-HCT). Then participants will receive allogeneic HCT (allo-HCT) transplant conditioning \[total lymphoid irradiation (TLI) + anti-thymocyte globulin (ATG)\] followed by allogenic PBSC (allo-HCT) obtained from a human leukocyte antigen (HLA)-matched or single mismatch filgrastim-mobilized donor. Participant allo-HCT transplant is to occur within 150 days of auto-HCT. Post-allo-HCT treatment includes cyclosporine + mycophenolate mofetil (MMF). Subject's participation ends if donor is not identified within 150 days. Pre-medication includes acetaminophen; diphenhydramine; hydrocortisone; \& methylprednisolone.
Autologous Peripheral Stem Cells STARTED	3
Autologous Peripheral Stem Cells COMPLETED	3
Autologous Peripheral Stem Cells NOT COMPLETED	0
Inter-treatment Period STARTED	3
Inter-treatment Period COMPLETED	2
Inter-treatment Period NOT COMPLETED	1
Allogeneic Peripheral Stem Cells STARTED	2
Allogeneic Peripheral Stem Cells COMPLETED	2
Allogeneic Peripheral Stem Cells NOT COMPLETED	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Auto-HCT Followed by Allo-HCT for Poor-risk DLBCL Participants will have peripheral blood stem cells (PBSC, aka progenitor / stem cells) mobilized to peripheral blood with rituximab, chemotherapy (cyclophosphamide or etoposide), and filgrastim; undergo apheresis to collect (self/autologous PBSC), and receive carmustine, etoposide, and cyclophosphamide as conditioning for PBSC infusion as a hematopoietic cell transplant (auto-HCT). Then participants will receive allogeneic HCT (allo-HCT) transplant conditioning \[total lymphoid irradiation (TLI) + anti-thymocyte globulin (ATG)\] followed by allogenic PBSC (allo-HCT) obtained from a human leukocyte antigen (HLA)-matched or single mismatch filgrastim-mobilized donor. Participant allo-HCT transplant is to occur within 150 days of auto-HCT. Post-allo-HCT treatment includes cyclosporine + mycophenolate mofetil (MMF). Subject's participation ends if donor is not identified within 150 days. Pre-medication includes acetaminophen; diphenhydramine; hydrocortisone; \& methylprednisolone.
Inter-treatment Period Disease progression	1

Baseline Characteristics

Phase 2 Poor Risk DLBCL of TLI and ATG Followed by Matched Allogeneic HT as Consolidation to Autologous HCT

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Auto-HCT Followed by Allo-HCT for Poor-risk DLBCL n=3 Participants Participants will have peripheral blood stem cells (PBSC, aka progenitor / stem cells) mobilized to peripheral blood with rituximab, chemotherapy (cyclophosphamide or etoposide), and filgrastim; undergo apheresis to collect (self/autologous PBSC), and receive carmustine, etoposide, and cyclophosphamide as conditioning for PBSC infusion as a hematopoietic cell transplant (auto-HCT). Then participants will receive allogeneic HCT (allo-HCT) transplant conditioning \[total lymphoid irradiation (TLI) + anti-thymocyte globulin (ATG)\] followed by allogenic PBSC (allo-HCT) obtained from a human leukocyte antigen (HLA)-matched or single mismatch filgrastim-mobilized donor. Participant allo-HCT transplant is to occur within 150 days of auto-HCT. Post-allo-HCT treatment includes cyclosporine + mycophenolate mofetil (MMF). Subject's participation ends if donor is not identified within 150 days. Pre-medication includes acetaminophen; diphenhydramine; hydrocortisone; \& methylprednisolone.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 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	0 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	2 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 48 months

Population: Reported data values are limited by protocol-specified upper boundary for the timeframe of this assessment.

Outcome measures

Outcome measures
Measure	Auto-HCT Followed by Allo-HCT for Poor-risk DLBCL n=2 Participants Participants will have peripheral blood stem cells (PBSC, aka progenitor / stem cells) mobilized to peripheral blood with rituximab, chemotherapy (cyclophosphamide or etoposide), and filgrastim; undergo apheresis to collect (self/autologous PBSC), and receive carmustine, etoposide, and cyclophosphamide as conditioning for PBSC infusion as a hematopoietic cell transplant (auto-HCT). Then participants will receive allogeneic HCT (allo-HCT) transplant conditioning \[total lymphoid irradiation (TLI) + anti-thymocyte globulin (ATG)\] followed by allogenic PBSC (allo-HCT) obtained from a human leukocyte antigen (HLA)-matched or single mismatch filgrastim-mobilized donor. Participant allo-HCT transplant is to occur within 150 days of auto-HCT. Post-allo-HCT treatment includes cyclosporine + mycophenolate mofetil (MMF). Subject's participation ends if donor is not identified within 150 days. Pre-medication includes acetaminophen; diphenhydramine; hydrocortisone; \& methylprednisolone.
Event-free Survival (EFS) Per Protocol	48 months Interval 48.0 to 48.0

SECONDARY outcome

Timeframe: within 1 month

Reported as neutrophil engraftment after autologous transplant, defined as absolute neutrophil count (ANC) \> 500/µL, counting from the day of transplant.

Outcome measures

Outcome measures
Measure	Auto-HCT Followed by Allo-HCT for Poor-risk DLBCL n=3 Participants Participants will have peripheral blood stem cells (PBSC, aka progenitor / stem cells) mobilized to peripheral blood with rituximab, chemotherapy (cyclophosphamide or etoposide), and filgrastim; undergo apheresis to collect (self/autologous PBSC), and receive carmustine, etoposide, and cyclophosphamide as conditioning for PBSC infusion as a hematopoietic cell transplant (auto-HCT). Then participants will receive allogeneic HCT (allo-HCT) transplant conditioning \[total lymphoid irradiation (TLI) + anti-thymocyte globulin (ATG)\] followed by allogenic PBSC (allo-HCT) obtained from a human leukocyte antigen (HLA)-matched or single mismatch filgrastim-mobilized donor. Participant allo-HCT transplant is to occur within 150 days of auto-HCT. Post-allo-HCT treatment includes cyclosporine + mycophenolate mofetil (MMF). Subject's participation ends if donor is not identified within 150 days. Pre-medication includes acetaminophen; diphenhydramine; hydrocortisone; \& methylprednisolone.
Median Time to Neutrophil Engraftment After Autologous Transplant	11 Days Interval 9.0 to 12.0

SECONDARY outcome

Timeframe: within 1 month

Reported as platelet engraftment after autologous transplant, defined as platelet count \> 20,000/µL, counting from the day of transplant.

Outcome measures

Outcome measures
Measure	Auto-HCT Followed by Allo-HCT for Poor-risk DLBCL n=3 Participants Participants will have peripheral blood stem cells (PBSC, aka progenitor / stem cells) mobilized to peripheral blood with rituximab, chemotherapy (cyclophosphamide or etoposide), and filgrastim; undergo apheresis to collect (self/autologous PBSC), and receive carmustine, etoposide, and cyclophosphamide as conditioning for PBSC infusion as a hematopoietic cell transplant (auto-HCT). Then participants will receive allogeneic HCT (allo-HCT) transplant conditioning \[total lymphoid irradiation (TLI) + anti-thymocyte globulin (ATG)\] followed by allogenic PBSC (allo-HCT) obtained from a human leukocyte antigen (HLA)-matched or single mismatch filgrastim-mobilized donor. Participant allo-HCT transplant is to occur within 150 days of auto-HCT. Post-allo-HCT treatment includes cyclosporine + mycophenolate mofetil (MMF). Subject's participation ends if donor is not identified within 150 days. Pre-medication includes acetaminophen; diphenhydramine; hydrocortisone; \& methylprednisolone.
Median Time to Platelet Engraftment After Autologous Transplant	19 Days Interval 15.0 to 19.0

SECONDARY outcome

Timeframe: within 1 month

Reported as neutrophil engraftment after allogeneic transplant, defined as absolute neutrophil count (ANC) \> 500/µL, counting from the day of transplant.

Outcome measures

Outcome measures
Measure	Auto-HCT Followed by Allo-HCT for Poor-risk DLBCL n=2 Participants Participants will have peripheral blood stem cells (PBSC, aka progenitor / stem cells) mobilized to peripheral blood with rituximab, chemotherapy (cyclophosphamide or etoposide), and filgrastim; undergo apheresis to collect (self/autologous PBSC), and receive carmustine, etoposide, and cyclophosphamide as conditioning for PBSC infusion as a hematopoietic cell transplant (auto-HCT). Then participants will receive allogeneic HCT (allo-HCT) transplant conditioning \[total lymphoid irradiation (TLI) + anti-thymocyte globulin (ATG)\] followed by allogenic PBSC (allo-HCT) obtained from a human leukocyte antigen (HLA)-matched or single mismatch filgrastim-mobilized donor. Participant allo-HCT transplant is to occur within 150 days of auto-HCT. Post-allo-HCT treatment includes cyclosporine + mycophenolate mofetil (MMF). Subject's participation ends if donor is not identified within 150 days. Pre-medication includes acetaminophen; diphenhydramine; hydrocortisone; \& methylprednisolone.
Median Time to Neutrophil Engraftment After Allogeneic Transplant	10.5 Days Interval 9.0 to 12.0

SECONDARY outcome

Timeframe: within 1 month

Population: Note: all participants engrafted platelets on the same day (see below for data values).

Reported as platelet engraftment after allogeneic transplant, defined as platelet count \> 20,000/µL, counting from the day of transplant.

Outcome measures

Outcome measures
Measure	Auto-HCT Followed by Allo-HCT for Poor-risk DLBCL n=2 Participants Participants will have peripheral blood stem cells (PBSC, aka progenitor / stem cells) mobilized to peripheral blood with rituximab, chemotherapy (cyclophosphamide or etoposide), and filgrastim; undergo apheresis to collect (self/autologous PBSC), and receive carmustine, etoposide, and cyclophosphamide as conditioning for PBSC infusion as a hematopoietic cell transplant (auto-HCT). Then participants will receive allogeneic HCT (allo-HCT) transplant conditioning \[total lymphoid irradiation (TLI) + anti-thymocyte globulin (ATG)\] followed by allogenic PBSC (allo-HCT) obtained from a human leukocyte antigen (HLA)-matched or single mismatch filgrastim-mobilized donor. Participant allo-HCT transplant is to occur within 150 days of auto-HCT. Post-allo-HCT treatment includes cyclosporine + mycophenolate mofetil (MMF). Subject's participation ends if donor is not identified within 150 days. Pre-medication includes acetaminophen; diphenhydramine; hydrocortisone; \& methylprednisolone.
Median Time to Platelet Engraftment After Allogeneic Transplant	10 Days Interval 10.0 to 10.0

SECONDARY outcome

Timeframe: 3 years

The incidence of chronic graft vs host disease (GvHD) is reported as any events within 3 years. Note that GvHD was assessed per investigator judgement. There was no protocol-specified criteria of GvHD.

Outcome measures

Outcome measures
Measure	Auto-HCT Followed by Allo-HCT for Poor-risk DLBCL n=3 Participants Participants will have peripheral blood stem cells (PBSC, aka progenitor / stem cells) mobilized to peripheral blood with rituximab, chemotherapy (cyclophosphamide or etoposide), and filgrastim; undergo apheresis to collect (self/autologous PBSC), and receive carmustine, etoposide, and cyclophosphamide as conditioning for PBSC infusion as a hematopoietic cell transplant (auto-HCT). Then participants will receive allogeneic HCT (allo-HCT) transplant conditioning \[total lymphoid irradiation (TLI) + anti-thymocyte globulin (ATG)\] followed by allogenic PBSC (allo-HCT) obtained from a human leukocyte antigen (HLA)-matched or single mismatch filgrastim-mobilized donor. Participant allo-HCT transplant is to occur within 150 days of auto-HCT. Post-allo-HCT treatment includes cyclosporine + mycophenolate mofetil (MMF). Subject's participation ends if donor is not identified within 150 days. Pre-medication includes acetaminophen; diphenhydramine; hydrocortisone; \& methylprednisolone.
Incidence of Chronic Graft vs Host Disease (GvHD)	0 Participants

SECONDARY outcome

Timeframe: 3 years

To evaluate the overall and transplant related mortality rate, reported as the number of subjects remaining alive 3 years after transplant.

Outcome measures

Outcome measures
Measure	Auto-HCT Followed by Allo-HCT for Poor-risk DLBCL n=3 Participants Participants will have peripheral blood stem cells (PBSC, aka progenitor / stem cells) mobilized to peripheral blood with rituximab, chemotherapy (cyclophosphamide or etoposide), and filgrastim; undergo apheresis to collect (self/autologous PBSC), and receive carmustine, etoposide, and cyclophosphamide as conditioning for PBSC infusion as a hematopoietic cell transplant (auto-HCT). Then participants will receive allogeneic HCT (allo-HCT) transplant conditioning \[total lymphoid irradiation (TLI) + anti-thymocyte globulin (ATG)\] followed by allogenic PBSC (allo-HCT) obtained from a human leukocyte antigen (HLA)-matched or single mismatch filgrastim-mobilized donor. Participant allo-HCT transplant is to occur within 150 days of auto-HCT. Post-allo-HCT treatment includes cyclosporine + mycophenolate mofetil (MMF). Subject's participation ends if donor is not identified within 150 days. Pre-medication includes acetaminophen; diphenhydramine; hydrocortisone; \& methylprednisolone.
Overall Survival (OS)	2 Participants

Adverse Events

Auto-HCT Followed by Allo-HCT for Poor-risk DLBCL

Serious events: 3 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Auto-HCT Followed by Allo-HCT for Poor-risk DLBCL n=3 participants at risk Participants will have peripheral blood stem cells (PBSC, aka progenitor / stem cells) mobilized to peripheral blood with rituximab, chemotherapy (cyclophosphamide or etoposide), and filgrastim; undergo apheresis to collect (self/autologous PBSC), and receive carmustine, etoposide, and cyclophosphamide as conditioning for PBSC infusion as a hematopoietic cell transplant (auto-HCT). Then participants will receive allogeneic HCT (allo-HCT) transplant conditioning \[total lymphoid irradiation (TLI) + anti-thymocyte globulin (ATG)\] followed by allogenic PBSC (allo-HCT) obtained from a human leukocyte antigen (HLA)-matched or single mismatch filgrastim-mobilized donor. Participant allo-HCT transplant is to occur within 150 days of auto-HCT. Post-allo-HCT treatment includes cyclosporine + mycophenolate mofetil (MMF). Subject's participation ends if donor is not identified within 150 days. Pre-medication includes acetaminophen; diphenhydramine; hydrocortisone; \& methylprednisolone.
Blood and lymphatic system disorders Platelet count decrease	33.3% 1/3 • Number of events 1 • 3 years
Blood and lymphatic system disorders Recurrent lymphoma	33.3% 1/3 • Number of events 2 • 3 years
Blood and lymphatic system disorders lymph nodes	33.3% 1/3 • Number of events 2 • 3 years
Gastrointestinal disorders Nausea	33.3% 1/3 • Number of events 1 • 3 years
Gastrointestinal disorders Mucositis	66.7% 2/3 • Number of events 2 • 3 years
Infections and infestations Febrile neutropenia	66.7% 2/3 • Number of events 2 • 3 years
Skin and subcutaneous tissue disorders Thrush	33.3% 1/3 • Number of events 1 • 3 years
Gastrointestinal disorders Constipation	33.3% 1/3 • Number of events 1 • 3 years
Respiratory, thoracic and mediastinal disorders Dyspnea	33.3% 1/3 • Number of events 1 • 3 years

Other adverse events

Other adverse events
Measure	Auto-HCT Followed by Allo-HCT for Poor-risk DLBCL n=3 participants at risk Participants will have peripheral blood stem cells (PBSC, aka progenitor / stem cells) mobilized to peripheral blood with rituximab, chemotherapy (cyclophosphamide or etoposide), and filgrastim; undergo apheresis to collect (self/autologous PBSC), and receive carmustine, etoposide, and cyclophosphamide as conditioning for PBSC infusion as a hematopoietic cell transplant (auto-HCT). Then participants will receive allogeneic HCT (allo-HCT) transplant conditioning \[total lymphoid irradiation (TLI) + anti-thymocyte globulin (ATG)\] followed by allogenic PBSC (allo-HCT) obtained from a human leukocyte antigen (HLA)-matched or single mismatch filgrastim-mobilized donor. Participant allo-HCT transplant is to occur within 150 days of auto-HCT. Post-allo-HCT treatment includes cyclosporine + mycophenolate mofetil (MMF). Subject's participation ends if donor is not identified within 150 days. Pre-medication includes acetaminophen; diphenhydramine; hydrocortisone; \& methylprednisolone.
Infections and infestations Bacteremia	33.3% 1/3 • Number of events 1 • 3 years
Infections and infestations facial cellulitis	33.3% 1/3 • Number of events 1 • 3 years
Infections and infestations Fever	100.0% 3/3 • Number of events 3 • 3 years
General disorders Headache	33.3% 1/3 • Number of events 1 • 3 years
Blood and lymphatic system disorders Hypermetabolic lymphadenopathy	33.3% 1/3 • Number of events 1 • 3 years
Blood and lymphatic system disorders Leukopenic	33.3% 1/3 • Number of events 1 • 3 years
Skin and subcutaneous tissue disorders Maculo-papular rash	33.3% 1/3 • Number of events 1 • 3 years
Gastrointestinal disorders Mucositis	33.3% 1/3 • Number of events 1 • 3 years
Musculoskeletal and connective tissue disorders Myalgia	33.3% 1/3 • Number of events 1 • 3 years
Gastrointestinal disorders Nausea	33.3% 1/3 • Number of events 1 • 3 years
Nervous system disorders Peripheral sensory neuropathy	33.3% 1/3 • Number of events 1 • 3 years
Respiratory, thoracic and mediastinal disorders Pleural effusion	33.3% 1/3 • Number of events 1 • 3 years
Respiratory, thoracic and mediastinal disorders Pneumonitis	33.3% 1/3 • Number of events 1 • 3 years
Infections and infestations Residual disease	33.3% 1/3 • Number of events 1 • 3 years
Respiratory, thoracic and mediastinal disorders Sinusitis	33.3% 1/3 • Number of events 1 • 3 years
Skin and subcutaneous tissue disorders Thrush	33.3% 1/3 • Number of events 1 • 3 years

Additional Information

Wen-Kai Weng, Assistant Professor of Medicine

Stanford University Medical Center

Phone: 650-723-7689

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place