Trial Outcomes & Findings for Phase 2 Study of Autologous Followed by Nonmyeloablative Allogeneic Transplantation Using TLI & ATG (NCT NCT00899847)

NCT ID: NCT00899847

Last Updated: 2017-10-20

Results Overview

To evaluate the incidence acute GvHD of this tandem autologous/allogeneic transplant setting

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 9 participants
• Primary outcome timeframe: 2 years after the last participant is enrolled.
• Results posted on: 2017-10-20

Participant Flow

Participant milestones

Measure	Autologous-Allogeneic Hematopoietic Stem Cell Transplant Study treatment is a high-dose sequential chemotherapy approach to hematopoietic stem cell (HSC) transplant that uses an autologous peripheral blood stem cell (auto-PBSC) transplant followed by allogeneic peripheral blood stem cell (allo-PBSC) transplant to evaluate improved graft vs host disease (GvHD) control. Participant auto-PBSC are mobilized with cyclophosphamide (also to provide cytoreduction) and filgrastim, followed by melphalan as an auto-PBSC conditioning agent, then auto-PBSC infusion. For the allo-PBSC transplant, donors are mobilized with filgrastim, and participants receive a regimen of total lymphoid irradiation and anti-thymocyte globulin (TLI/ATG), followed by infusion of donor allo-PBSC. Solumedrol, diphenhydramine, acetaminophen, and hydrocortisone are administered as premedications, and rabbit anti-thymocyte globulin (ATG) plus mycophenolate mofetil (MMF) are administered for post-allo-PBSC immunosuppression.
Overall Study STARTED	9
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure

Autologous-Allogeneic Hematopoietic Stem Cell Transplant Study treatment is a high-dose sequential chemotherapy approach to hematopoietic stem cell (HSC) transplant that uses an autologous peripheral blood stem cell (auto-PBSC) transplant followed by allogeneic peripheral blood stem cell (allo-PBSC) transplant to evaluate improved graft vs host disease (GvHD) control. Participant auto-PBSC are mobilized with cyclophosphamide (also to provide cytoreduction) and filgrastim, followed by melphalan as an auto-PBSC conditioning agent, then auto-PBSC infusion. For the allo-PBSC transplant, donors are mobilized with filgrastim, and participants receive a regimen of total lymphoid irradiation and anti-thymocyte globulin (TLI/ATG), followed by infusion of donor allo-PBSC. Solumedrol, diphenhydramine, acetaminophen, and hydrocortisone are administered as premedications, and rabbit anti-thymocyte globulin (ATG) plus mycophenolate mofetil (MMF) are administered for post-allo-PBSC immunosuppression.

Overall Study Lack of suitable allogeneic donor

2

Baseline Characteristics

Phase 2 Study of Autologous Followed by Nonmyeloablative Allogeneic Transplantation Using TLI & ATG

Baseline characteristics by cohort

Measure	Autologous-Allogeneic Hematopoietic Stem Cell Transplant n=9 Participants A high-dose sequential chemotherapy approach with cyclophosphamide and etoposide followed by granulocyte colony stimulating factor (G-CSF) for collection of peripheral blood progenitor cells as well as for cytoreduction. Total Lymphoid irradiation and anti-thymocyte globulin (TLI/ATG).The preparatory regimens use BCNU and melphalan.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	54 years n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 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	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 years after the last participant is enrolled.

Population: Due to the significance of the allo-PBSC transplant as a component to the treatment plan, participants who did not receive allo-PBSC are not included.

To evaluate the incidence acute GvHD of this tandem autologous/allogeneic transplant setting

Outcome measures

Measure

Autologous-Allogeneic Hematopoietic Stem Cell Transplant n=7 Participants A high-dose sequential chemotherapy approach with cyclophosphamide and etoposide followed by granulocyte colony stimulating factor (G-CSF) for collection of peripheral blood progenitor cells as well as for cytoreduction. Total Lymphoid irradiation and anti-thymocyte globulin (TLI/ATG).The preparatory regimens use BCNU and melphalan.

Incidence of Graft Versus Host Disease (GvHD)

1 Participants

SECONDARY outcome

Timeframe: 1 month

Population: Includes all study participants

Engraftment is assessed as:

• Neutrophil engraftment is > 0.5 x 10⁹/L after cytopenia
• Platelet engraftment is > 20 x 10⁹/L after cytopenia

Outcome measures

Measure	Autologous-Allogeneic Hematopoietic Stem Cell Transplant n=9 Participants A high-dose sequential chemotherapy approach with cyclophosphamide and etoposide followed by granulocyte colony stimulating factor (G-CSF) for collection of peripheral blood progenitor cells as well as for cytoreduction. Total Lymphoid irradiation and anti-thymocyte globulin (TLI/ATG).The preparatory regimens use BCNU and melphalan.
Median Time to Engraftment After Auto-PBSC Transplant Neutrophil Engraftment	11 Days Interval 10.0 to 12.0
Median Time to Engraftment After Auto-PBSC Transplant Platelet Engraftment	15 Days Interval 10.0 to 20.0

SECONDARY outcome

Timeframe: 1 month

Population: Due to the less intensive conditioning before allo-PBSC, only 2 participants experienced cytopenia, and thus only 2 participants could be evaluated for engraftment after allo-PBSC.

Engraftment is assessed as:

• Neutrophil engraftment is > 0.5 x 10⁹/L after cytopenia
• Platelet engraftment is > 20 x 10⁹/L after cytopenia

Outcome measures

Measure	Autologous-Allogeneic Hematopoietic Stem Cell Transplant n=2 Participants A high-dose sequential chemotherapy approach with cyclophosphamide and etoposide followed by granulocyte colony stimulating factor (G-CSF) for collection of peripheral blood progenitor cells as well as for cytoreduction. Total Lymphoid irradiation and anti-thymocyte globulin (TLI/ATG).The preparatory regimens use BCNU and melphalan.
Median Time to Engraftment After Allo-PBSC Transplant Neutrophil Engraftment	24 Days Interval 24.0 to 24.0
Median Time to Engraftment After Allo-PBSC Transplant Platelet Engraftment	10 Days Interval 10.0 to 10.0

SECONDARY outcome

Timeframe: 1 year

Population: Includes all study participants

Overall response rate (ORR) = Complete Response Rate (CRR) + Partial Response Rate (PRR)

Outcome measures

Measure

Autologous-Allogeneic Hematopoietic Stem Cell Transplant n=9 Participants A high-dose sequential chemotherapy approach with cyclophosphamide and etoposide followed by granulocyte colony stimulating factor (G-CSF) for collection of peripheral blood progenitor cells as well as for cytoreduction. Total Lymphoid irradiation and anti-thymocyte globulin (TLI/ATG).The preparatory regimens use BCNU and melphalan.

Overall Response Rate (ORR)

7 Participants

SECONDARY outcome

Timeframe: 1 year

Population: Includes all study participants

Complete response rate (CRR) was assessed as all of:

• Negative immunoflixation on the serum and urine
• Disappearance of any soft tissue plasmacytomas
• < 5% plasma cells in bone marrow

Outcome measures

Measure

Autologous-Allogeneic Hematopoietic Stem Cell Transplant n=9 Participants A high-dose sequential chemotherapy approach with cyclophosphamide and etoposide followed by granulocyte colony stimulating factor (G-CSF) for collection of peripheral blood progenitor cells as well as for cytoreduction. Total Lymphoid irradiation and anti-thymocyte globulin (TLI/ATG).The preparatory regimens use BCNU and melphalan.

Complete Response Rate (CRR)

3 Participants

SECONDARY outcome

Timeframe: 1 year

Population: Includes all study participants

Partial response rate (PRR) was assessed as

• > 50% reduction in serum M-protein plus urine M-protein reduction by 90% or < 200 mg/24 hr
• If serum M-protein is not measurable, then > 50% reduction in the involved serum free light chain
• If involved serum free light chain is not measurable, then > 50% reduction in the bone marrow plasma cell percentage + > 50% reduction in the size of any soft tissue plasmacytoma.

Outcome measures

Measure

Autologous-Allogeneic Hematopoietic Stem Cell Transplant n=9 Participants A high-dose sequential chemotherapy approach with cyclophosphamide and etoposide followed by granulocyte colony stimulating factor (G-CSF) for collection of peripheral blood progenitor cells as well as for cytoreduction. Total Lymphoid irradiation and anti-thymocyte globulin (TLI/ATG).The preparatory regimens use BCNU and melphalan.

Partial Response Rate (PRR)

4 Participants

SECONDARY outcome

Timeframe: 2 years after the last participant is enrolled

Population: Includes all study participants

To evaluate the graft versus myeloma effect by monitoring rate of event-free survival (EFS)

Outcome measures

Measure

Autologous-Allogeneic Hematopoietic Stem Cell Transplant n=9 Participants A high-dose sequential chemotherapy approach with cyclophosphamide and etoposide followed by granulocyte colony stimulating factor (G-CSF) for collection of peripheral blood progenitor cells as well as for cytoreduction. Total Lymphoid irradiation and anti-thymocyte globulin (TLI/ATG).The preparatory regimens use BCNU and melphalan.

Event-free Survival (EFS)

44 percentage of participants Interval 14.0 to 71.0

SECONDARY outcome

Timeframe: 2 years after the last participant is enrolled

Population: Includes all study participants

To evaluate the graft versus myeloma effect by monitoring rate of overall survival (OS)

Outcome measures

Measure

Autologous-Allogeneic Hematopoietic Stem Cell Transplant n=9 Participants A high-dose sequential chemotherapy approach with cyclophosphamide and etoposide followed by granulocyte colony stimulating factor (G-CSF) for collection of peripheral blood progenitor cells as well as for cytoreduction. Total Lymphoid irradiation and anti-thymocyte globulin (TLI/ATG).The preparatory regimens use BCNU and melphalan.

Overall Survival (OS)

67 percentage of participants Interval 28.0 to 87.0

Adverse Events

Autologous-Allogeneic Hematopoietic Stem Cell Transplant

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Autologous-Allogeneic Hematopoietic Stem Cell Transplant n=9 participants at risk A high-dose sequential chemotherapy approach with cyclophosphamide and etoposide followed by granulocyte colony stimulating factor (G-CSF) for collection of peripheral blood progenitor cells as well as for cytoreduction. Total Lymphoid irradiation and anti-thymocyte globulin (TLI/ATG).The preparatory regimens use BCNU and melphalan.
Vascular disorders Pulmonary Embolism	11.1% 1/9 • Number of events 1 • 2 years
Vascular disorders Deep Vein Thrombosis	11.1% 1/9 • Number of events 1 • 2 years

Other adverse events

Adverse event data not reported

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