Trial Outcomes & Findings for Autologous Followed by Non-myeloablative Allogeneic Transplantation for Non-Hodgkin's Lymphoma (NCT NCT00481832)

NCT ID: NCT00481832

Last Updated: 2018-02-14

Results Overview

Event-free survival (EFS) as determined for participants who receive both planned transplants, for a minimum of 3 years. Events are defined as "disease progression/relapse" and "death of all causes".

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 50 participants
• Primary outcome timeframe: 3 years
• Results posted on: 2018-02-14

Participant Flow

Participant milestones

Measure	T & B Cell Mobilization Auto & Allo HCT A transplant regimen that conditions the subjects using total lymphoid irradiation (TLI) and anti-thymocyte globulin(ATG) which will reduce acute graft-vs-host disease to negligible rates while maintaining the anti-tumor graft vs lymphoma GvL benefit. Along with TLI/ATG regiment; Solumedrol will be used as pre-medication and anti-emetic for any side effects. For stem cell mobilization, participants will be given either B Cell NLH or T Cell NHL. Before the filgrastim (G-CSF) mobilized PBPC infusion: acetaminophen, diphenhydramine and hydrocortisone will also be given as another set of pre-medications. BCNU, Etoposide, and Cyclophosphamide will be used as a preparative regimen. Cyclosporine and mycophenolate mofetil will be administered as an immunosuppressant after transplantation. Lastly, rituximab will be infused at the end of the transplantation regimen.
Enrollment STARTED	50
Enrollment COMPLETED	40
Enrollment NOT COMPLETED	10
Autologous Hematopoietic Cell Transplant STARTED	40
Autologous Hematopoietic Cell Transplant COMPLETED	40
Autologous Hematopoietic Cell Transplant NOT COMPLETED	0
Inter-transplant Period STARTED	40
Inter-transplant Period COMPLETED	13
Inter-transplant Period NOT COMPLETED	27
Allogenic Hematopoietic Cell Transplant STARTED	13
Allogenic Hematopoietic Cell Transplant COMPLETED	13
Allogenic Hematopoietic Cell Transplant NOT COMPLETED	0

Reasons for withdrawal

Measure	T & B Cell Mobilization Auto & Allo HCT A transplant regimen that conditions the subjects using total lymphoid irradiation (TLI) and anti-thymocyte globulin(ATG) which will reduce acute graft-vs-host disease to negligible rates while maintaining the anti-tumor graft vs lymphoma GvL benefit. Along with TLI/ATG regiment; Solumedrol will be used as pre-medication and anti-emetic for any side effects. For stem cell mobilization, participants will be given either B Cell NLH or T Cell NHL. Before the filgrastim (G-CSF) mobilized PBPC infusion: acetaminophen, diphenhydramine and hydrocortisone will also be given as another set of pre-medications. BCNU, Etoposide, and Cyclophosphamide will be used as a preparative regimen. Cyclosporine and mycophenolate mofetil will be administered as an immunosuppressant after transplantation. Lastly, rituximab will be infused at the end of the transplantation regimen.
Enrollment Physician Decision	8
Enrollment Unable to collect enough stem cells	2
Inter-transplant Period Adverse Event	4
Inter-transplant Period Death	3
Inter-transplant Period Physician Decision	4
Inter-transplant Period Disease relapse	11
Inter-transplant Period Lack of allogeneic donor	5

Baseline Characteristics

Autologous Followed by Non-myeloablative Allogeneic Transplantation for Non-Hodgkin's Lymphoma

Baseline characteristics by cohort

Measure	T & B Cell Mobilization Auto & Allo HCT n=50 Participants A transplant regimen that conditions the subjects using total lymphoid irradiation (TLI) and anti-thymocyte globulin(ATG) which will reduce acute graft-vs-host disease to negligible rates while maintaining the anti-tumor graft vs lymphoma GvL benefit. Along with TLI/ATG regiment; Solumedrol will be used as pre-medication and anti-emetic for any side effects. For stem cell mobilization, participants will be given either B Cell NLH or T Cell NHL. Before the filgrastim (G-CSF) mobilized PBPC infusion: acetaminophen, diphenhydramine and hydrocortisone will also be given as another set of pre-medications. BCNU, Etoposide, and Cyclophosphamide will be used as a preparative regimen. Cyclosporine and mycophenolate mofetil will be administered as an immunosuppressant after transplantation. Lastly, rituximab will be infused at the end of the transplantation regimen.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	43 Participants n=5 Participants
Age, Categorical >=65 years	7 Participants n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	44 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 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	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	38 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: 3 years

Event-free survival (EFS) as determined for participants who receive both planned transplants, for a minimum of 3 years.

Events are defined as "disease progression/relapse" and "death of all causes".

Outcome measures

Measure

T & B Cell Mobilization Auto & Allo HCT n=13 Participants A transplant regimen that conditions the subjects using total lymphoid irradiation (TLI) and anti-thymocyte globulin(ATG) which will reduce acute graft-vs-host disease to negligible rates while maintaining the anti-tumor graft vs lymphoma GvL benefit. Along with TLI/ATG regiment; Solumedrol will be used as pre-medication and anti-emetic for any side effects. For stem cell mobilization, participants will be given either B Cell NLH or T Cell NHL. Before the filgrastim (G-CSF) mobilized PBPC infusion: acetaminophen, diphenhydramine and hydrocortisone will also be given as another set of pre-medications. BCNU, Etoposide, and Cyclophosphamide will be used as a preparative regimen. Cyclosporine and mycophenolate mofetil will be administered as an immunosuppressant after transplantation. Lastly, rituximab will be infused at the end of the transplantation regimen.

Event-free Survival (EFS)

35 percentage of participants Interval 27.0 to 80.0

SECONDARY outcome

Timeframe: 3 years

Interstitial pneumonitis (IP) is a risk associated with high-dose carmustine (BCNU) or other chemotherapy drugs used for transplantation. IP is diagnosed by 1) a decrease of >25% in DLCO compared with pre-transplant PFT DLCO values or 2) a drop of 7% or more in oxygen saturation after exertion.

Outcome measures

Measure

T & B Cell Mobilization Auto & Allo HCT n=40 Participants A transplant regimen that conditions the subjects using total lymphoid irradiation (TLI) and anti-thymocyte globulin(ATG) which will reduce acute graft-vs-host disease to negligible rates while maintaining the anti-tumor graft vs lymphoma GvL benefit. Along with TLI/ATG regiment; Solumedrol will be used as pre-medication and anti-emetic for any side effects. For stem cell mobilization, participants will be given either B Cell NLH or T Cell NHL. Before the filgrastim (G-CSF) mobilized PBPC infusion: acetaminophen, diphenhydramine and hydrocortisone will also be given as another set of pre-medications. BCNU, Etoposide, and Cyclophosphamide will be used as a preparative regimen. Cyclosporine and mycophenolate mofetil will be administered as an immunosuppressant after transplantation. Lastly, rituximab will be infused at the end of the transplantation regimen.

Incidence of Chemotherapy-associated Pneumonitis

16 Participants

SECONDARY outcome

Timeframe: 3 years

Relapse rate (disease recurrence) 3 years after transplant, for participants who received both transplants, as determined by Kaplan-Meier estimation.

Outcome measures

Measure

T & B Cell Mobilization Auto & Allo HCT n=13 Participants A transplant regimen that conditions the subjects using total lymphoid irradiation (TLI) and anti-thymocyte globulin(ATG) which will reduce acute graft-vs-host disease to negligible rates while maintaining the anti-tumor graft vs lymphoma GvL benefit. Along with TLI/ATG regiment; Solumedrol will be used as pre-medication and anti-emetic for any side effects. For stem cell mobilization, participants will be given either B Cell NLH or T Cell NHL. Before the filgrastim (G-CSF) mobilized PBPC infusion: acetaminophen, diphenhydramine and hydrocortisone will also be given as another set of pre-medications. BCNU, Etoposide, and Cyclophosphamide will be used as a preparative regimen. Cyclosporine and mycophenolate mofetil will be administered as an immunosuppressant after transplantation. Lastly, rituximab will be infused at the end of the transplantation regimen.

Relapse Rate

27 percentage of participants Interval 10.0 to 62.0

SECONDARY outcome

Timeframe: 3 years

Overall Survival (OS) 3 years after transplant, for participants who received both transplants, as determined by Kaplan-Meier estimation.

Outcome measures

Measure

T & B Cell Mobilization Auto & Allo HCT n=13 Participants A transplant regimen that conditions the subjects using total lymphoid irradiation (TLI) and anti-thymocyte globulin(ATG) which will reduce acute graft-vs-host disease to negligible rates while maintaining the anti-tumor graft vs lymphoma GvL benefit. Along with TLI/ATG regiment; Solumedrol will be used as pre-medication and anti-emetic for any side effects. For stem cell mobilization, participants will be given either B Cell NLH or T Cell NHL. Before the filgrastim (G-CSF) mobilized PBPC infusion: acetaminophen, diphenhydramine and hydrocortisone will also be given as another set of pre-medications. BCNU, Etoposide, and Cyclophosphamide will be used as a preparative regimen. Cyclosporine and mycophenolate mofetil will be administered as an immunosuppressant after transplantation. Lastly, rituximab will be infused at the end of the transplantation regimen.

Overall Survival (OS)

57 percentage of participants Interval 26.0 to 79.0

SECONDARY outcome

Timeframe: 6 Months

Population: Only 13 participants received both therapies and were evaluated for GVHD

The development of GvHD in vaccinated patients of any grade and at 6 months.

Outcome measures

Measure

T & B Cell Mobilization Auto & Allo HCT n=13 Participants A transplant regimen that conditions the subjects using total lymphoid irradiation (TLI) and anti-thymocyte globulin(ATG) which will reduce acute graft-vs-host disease to negligible rates while maintaining the anti-tumor graft vs lymphoma GvL benefit. Along with TLI/ATG regiment; Solumedrol will be used as pre-medication and anti-emetic for any side effects. For stem cell mobilization, participants will be given either B Cell NLH or T Cell NHL. Before the filgrastim (G-CSF) mobilized PBPC infusion: acetaminophen, diphenhydramine and hydrocortisone will also be given as another set of pre-medications. BCNU, Etoposide, and Cyclophosphamide will be used as a preparative regimen. Cyclosporine and mycophenolate mofetil will be administered as an immunosuppressant after transplantation. Lastly, rituximab will be infused at the end of the transplantation regimen.

Incidence of Acute Graft Versus Host Disease (GvHD)

3 Participants

SECONDARY outcome

Timeframe: 3 years

The development of GvHD in vaccinated patients of any grade at 6 months.

Outcome measures

Measure

T & B Cell Mobilization Auto & Allo HCT n=13 Participants A transplant regimen that conditions the subjects using total lymphoid irradiation (TLI) and anti-thymocyte globulin(ATG) which will reduce acute graft-vs-host disease to negligible rates while maintaining the anti-tumor graft vs lymphoma GvL benefit. Along with TLI/ATG regiment; Solumedrol will be used as pre-medication and anti-emetic for any side effects. For stem cell mobilization, participants will be given either B Cell NLH or T Cell NHL. Before the filgrastim (G-CSF) mobilized PBPC infusion: acetaminophen, diphenhydramine and hydrocortisone will also be given as another set of pre-medications. BCNU, Etoposide, and Cyclophosphamide will be used as a preparative regimen. Cyclosporine and mycophenolate mofetil will be administered as an immunosuppressant after transplantation. Lastly, rituximab will be infused at the end of the transplantation regimen.

Incidence of Chronic Graft Versus Host Disease (GvHD)

3 Participants

SECONDARY outcome

Timeframe: 3 years

Overall mortality is determined by Kaplan-Meier estimation. The overall morality rate is expressed as the percentage of patients who died for any reason, including disease-related death.

Outcome measures

Measure

T & B Cell Mobilization Auto & Allo HCT n=40 Participants A transplant regimen that conditions the subjects using total lymphoid irradiation (TLI) and anti-thymocyte globulin(ATG) which will reduce acute graft-vs-host disease to negligible rates while maintaining the anti-tumor graft vs lymphoma GvL benefit. Along with TLI/ATG regiment; Solumedrol will be used as pre-medication and anti-emetic for any side effects. For stem cell mobilization, participants will be given either B Cell NLH or T Cell NHL. Before the filgrastim (G-CSF) mobilized PBPC infusion: acetaminophen, diphenhydramine and hydrocortisone will also be given as another set of pre-medications. BCNU, Etoposide, and Cyclophosphamide will be used as a preparative regimen. Cyclosporine and mycophenolate mofetil will be administered as an immunosuppressant after transplantation. Lastly, rituximab will be infused at the end of the transplantation regimen.

Overall Mortality Rate

56 percentage of participants Interval 42.0 to 71.0

SECONDARY outcome

Timeframe: up to 45 days

Complete blood counts were measured daily after allogeneic transplant. Time to neutrophil engraftment is defined as the number of days it takes to reach an absolute neutrophils count (ANC) >500, counting from the day of transplant.

Outcome measures

Measure

T & B Cell Mobilization Auto & Allo HCT n=13 Participants A transplant regimen that conditions the subjects using total lymphoid irradiation (TLI) and anti-thymocyte globulin(ATG) which will reduce acute graft-vs-host disease to negligible rates while maintaining the anti-tumor graft vs lymphoma GvL benefit. Along with TLI/ATG regiment; Solumedrol will be used as pre-medication and anti-emetic for any side effects. For stem cell mobilization, participants will be given either B Cell NLH or T Cell NHL. Before the filgrastim (G-CSF) mobilized PBPC infusion: acetaminophen, diphenhydramine and hydrocortisone will also be given as another set of pre-medications. BCNU, Etoposide, and Cyclophosphamide will be used as a preparative regimen. Cyclosporine and mycophenolate mofetil will be administered as an immunosuppressant after transplantation. Lastly, rituximab will be infused at the end of the transplantation regimen.

Median Time to Neutrophile Engraftment

17 Days Interval 9.0 to 26.0

SECONDARY outcome

Timeframe: Up to 1 year

Achieving full donor chimerism (donor T cells >95%): Blood was sent for donor cell percentage measured by short tandem repeat (STR) at post-transplant Day 30; Day 60; Day 90; Day 120; Day 180; Day 270; and Day 360. Full donor chimerism is defined as donor CD3+ cells > 95%.

Outcome measures

Measure

T & B Cell Mobilization Auto & Allo HCT n=13 Participants A transplant regimen that conditions the subjects using total lymphoid irradiation (TLI) and anti-thymocyte globulin(ATG) which will reduce acute graft-vs-host disease to negligible rates while maintaining the anti-tumor graft vs lymphoma GvL benefit. Along with TLI/ATG regiment; Solumedrol will be used as pre-medication and anti-emetic for any side effects. For stem cell mobilization, participants will be given either B Cell NLH or T Cell NHL. Before the filgrastim (G-CSF) mobilized PBPC infusion: acetaminophen, diphenhydramine and hydrocortisone will also be given as another set of pre-medications. BCNU, Etoposide, and Cyclophosphamide will be used as a preparative regimen. Cyclosporine and mycophenolate mofetil will be administered as an immunosuppressant after transplantation. Lastly, rituximab will be infused at the end of the transplantation regimen.

Achieving Full Donor Chimerism

10 Participants

SECONDARY outcome

Timeframe: Up to 45 days

Complete blood counts were measured daily after allogeneic transplant. Time to platelet engraftment is defined as the number of days it takes to reach platelet count >20,000, counting from the day of transplant.

Outcome measures

Measure

T & B Cell Mobilization Auto & Allo HCT n=13 Participants A transplant regimen that conditions the subjects using total lymphoid irradiation (TLI) and anti-thymocyte globulin(ATG) which will reduce acute graft-vs-host disease to negligible rates while maintaining the anti-tumor graft vs lymphoma GvL benefit. Along with TLI/ATG regiment; Solumedrol will be used as pre-medication and anti-emetic for any side effects. For stem cell mobilization, participants will be given either B Cell NLH or T Cell NHL. Before the filgrastim (G-CSF) mobilized PBPC infusion: acetaminophen, diphenhydramine and hydrocortisone will also be given as another set of pre-medications. BCNU, Etoposide, and Cyclophosphamide will be used as a preparative regimen. Cyclosporine and mycophenolate mofetil will be administered as an immunosuppressant after transplantation. Lastly, rituximab will be infused at the end of the transplantation regimen.

Median Time to Platelet Engraftment

11 Days Interval 1.0 to 41.0

Adverse Events

T & B Cell Mobilization Auto & Allo HCT

Serious events: 5 serious events

Other events: 4 other events

Deaths: 24 deaths

Serious adverse events

Measure	T & B Cell Mobilization Auto & Allo HCT n=50 participants at risk A transplant regimen that conditions the subjects using total lymphoid irradiation (TLI) and anti-thymocyte globulin(ATG) which will reduce acute graft-vs-host disease to negligible rates while maintaining the anti-tumor graft vs lymphoma GvL benefit. Along with TLI/ATG regiment; Solumedrol will be used as pre-medication and anti-emetic for any side effects. For stem cell mobilization, participants will be given either B Cell NLH or T Cell NHL. Before the filgrastim (G-CSF) mobilized PBPC infusion: acetaminophen, diphenhydramine and hydrocortisone will also be given as another set of pre-medications. BCNU, Etoposide, and Cyclophosphamide will be used as a preparative regimen. Cyclosporine and mycophenolate mofetil will be administered as an immunosuppressant after transplantation. Lastly, rituximab will be infused at the end of the transplantation regimen.
Respiratory, thoracic and mediastinal disorders Viral Pneumonitis	4.0% 2/50 • Number of events 2 • 3 years
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.0% 1/50 • Number of events 1 • 3 years
Respiratory, thoracic and mediastinal disorders Adult Respiratory Distress Syndrome	2.0% 1/50 • Number of events 1 • 3 years
Renal and urinary disorders Renal/ Liver failure	2.0% 1/50 • Number of events 1 • 3 years

Other adverse events

Measure	T & B Cell Mobilization Auto & Allo HCT n=50 participants at risk A transplant regimen that conditions the subjects using total lymphoid irradiation (TLI) and anti-thymocyte globulin(ATG) which will reduce acute graft-vs-host disease to negligible rates while maintaining the anti-tumor graft vs lymphoma GvL benefit. Along with TLI/ATG regiment; Solumedrol will be used as pre-medication and anti-emetic for any side effects. For stem cell mobilization, participants will be given either B Cell NLH or T Cell NHL. Before the filgrastim (G-CSF) mobilized PBPC infusion: acetaminophen, diphenhydramine and hydrocortisone will also be given as another set of pre-medications. BCNU, Etoposide, and Cyclophosphamide will be used as a preparative regimen. Cyclosporine and mycophenolate mofetil will be administered as an immunosuppressant after transplantation. Lastly, rituximab will be infused at the end of the transplantation regimen.
Blood and lymphatic system disorders Decreased platelet count	4.0% 2/50 • Number of events 2 • 3 years
Respiratory, thoracic and mediastinal disorders Decreased lung persusion capacity	2.0% 1/50 • Number of events 1 • 3 years
Blood and lymphatic system disorders Decreased neutrophile count	2.0% 1/50 • Number of events 1 • 3 years

Additional Information

Wen-Kai Weng, MD; Associate Professor of Medicine

Stanford University School of Med

Phone: 650-723-7689

Email: wkweng@stanford.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place