Trial Outcomes & Findings for Visilizumab for the Prevention of Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation (NCT NCT00720629)

Results Overview

Cumulative Incidence of Grade II-IV Acute GVHD Score at 100 Days. Investigators had planned to assess whether the grade of acute GVHD was decreased by visilizumab in combination with tacrolimus/methotrexate compared to standard treatment with thymoglobulin/tacrolimus/methotrexate after transplantation from unrelated mismatched donors, from day of transplant up to one year. Study was closed during the first treatment stage and did not proceed to the second stage treatment comparison to ATG in combination with tacrolimus/methotrexate as originally planned. Overall GVHD Grade: From Filipovich AH, Weisdorf D, Pavletic S, etal: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. Diagnosis and Staging Working Group Report. Biology of Blood and Marrow Transplantation 11:945-955 (2005). Grade I: Skin Stage 1-2, Liver Stage 0, Gut State 0; Grade II: Skin Stage 3 or, Liver Stage 1 or, Gut Stage 1; Grade II

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

8 participants

Primary outcome timeframe

100 days

Results posted on

2014-07-18

Participant Flow

Participants were enrolled at Moffitt Cancer Center between February 2008 and April 2010.

The study was closed during the single-arm, first stage and did not proceed to the second stage comparison to antithymocyte globulin (ATG) in combination with tacrolimus/methotrexate as originally planned.

Participant milestones

Participant milestones
Measure	First Study Stage: Study Treatment Visilizumab, Tacrolimus and Methotrexate. All participants.
Overall Study STARTED	8
Overall Study COMPLETED	8
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Visilizumab for the Prevention of Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	First Stage: Study Treatment n=8 Participants Visilizumab, Tacrolimus and Methotrexate. All participants.
Age, Continuous	36.5 years n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants

PRIMARY outcome

Timeframe: 100 days

Population: All participants

Cumulative Incidence of Grade II-IV Acute GVHD Score at 100 Days. Investigators had planned to assess whether the grade of acute GVHD was decreased by visilizumab in combination with tacrolimus/methotrexate compared to standard treatment with thymoglobulin/tacrolimus/methotrexate after transplantation from unrelated mismatched donors, from day of transplant up to one year. Study was closed during the first treatment stage and did not proceed to the second stage treatment comparison to ATG in combination with tacrolimus/methotrexate as originally planned. Overall GVHD Grade: From Filipovich AH, Weisdorf D, Pavletic S, etal: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. Diagnosis and Staging Working Group Report. Biology of Blood and Marrow Transplantation 11:945-955 (2005). Grade I: Skin Stage 1-2, Liver Stage 0, Gut State 0; Grade II: Skin Stage 3 or, Liver Stage 1 or, Gut Stage 1; Grade II

Outcome measures

Outcome measures
Measure	First Study Stage: Study Treatment n=8 Participants Visilizumab, Tacrolimus and Methotrexate. All participants.	5 Year Analysis Group First Study Stage: Study Treatment. Visilizumab, Tacrolimus and Methotrexate.
Number of Participants With Grade II-IV Acute Graft-versus-Host Disease (GVHD) Score at 100 Days Grade II-IV Acute GVHD	8 participants	—
Number of Participants With Grade II-IV Acute Graft-versus-Host Disease (GVHD) Score at 100 Days Grade I-II Acute GVHD	6 participants	—
Number of Participants With Grade II-IV Acute Graft-versus-Host Disease (GVHD) Score at 100 Days Grade III-IV Acute GVHD	2 participants	—

SECONDARY outcome

Timeframe: 3 months

Population: All participants

Number of participants who reactivated EBV. Patients had their plasma tested once weekly using the TaqMan polymerase chain reaction (PCR) for quantitative determination of EBV-DNA for 6 weeks. Plasma levels \> 1000 copies per ml plasma were scored as positive.

Outcome measures

Outcome measures
Measure	First Study Stage: Study Treatment n=8 Participants Visilizumab, Tacrolimus and Methotrexate. All participants.	5 Year Analysis Group First Study Stage: Study Treatment. Visilizumab, Tacrolimus and Methotrexate.
Incidence of Epstein-Barr Virus (EBV) Reactivation	6 participants	—

SECONDARY outcome

Timeframe: 100 days

Population: Reactivated EBV participants

Participants who developed plasma EBV-DNA of \>1000 copies/mL on any tests received rituximab. Incidence of Rituximab Response: Reactivated EBV participants whose plasma titers cleared after rituximab, without post-transplant lymphoproliferative disorder (PTLD).

Outcome measures

Outcome measures
Measure	First Study Stage: Study Treatment n=6 Participants Visilizumab, Tacrolimus and Methotrexate. All participants.	5 Year Analysis Group First Study Stage: Study Treatment. Visilizumab, Tacrolimus and Methotrexate.
Incidence of Rituximab Response to Reactivated EBV Without PTLD	6 participants	—

SECONDARY outcome

Timeframe: At 2 years and 5 years

Population: Participants who had died by Year 2 and additional participants who had died by Year 5.

Median OS in days. Survival was measured from the time of transplant to the time of death.

Outcome measures

Outcome measures
Measure	First Study Stage: Study Treatment n=6 Participants Visilizumab, Tacrolimus and Methotrexate. All participants.	5 Year Analysis Group n=2 Participants First Study Stage: Study Treatment. Visilizumab, Tacrolimus and Methotrexate.
Overall Survival (OS)	197 days Interval 150.0 to 643.0	1803 days Interval 1791.0 to 1816.0

SECONDARY outcome

Timeframe: At 1 - 2 hours

Population: All participants

Mean Cmax (±SD)

Outcome measures

Outcome measures
Measure	First Study Stage: Study Treatment n=8 Participants Visilizumab, Tacrolimus and Methotrexate. All participants.	5 Year Analysis Group First Study Stage: Study Treatment. Visilizumab, Tacrolimus and Methotrexate.
Pharmacodynamics of Visilizumab - Test 1	1564 ng/mL Standard Deviation 428	—

SECONDARY outcome

Timeframe: Up to 205 hours

Population: All participants

Mean terminal half-life (±SD)

Outcome measures

Outcome measures
Measure	First Study Stage: Study Treatment n=8 Participants Visilizumab, Tacrolimus and Methotrexate. All participants.	5 Year Analysis Group First Study Stage: Study Treatment. Visilizumab, Tacrolimus and Methotrexate.
Pharmacodynamics of Visilizumab - Test 2	157 hours Standard Deviation 48	—

Adverse Events

First Stage: Study Treatment

Serious events: 8 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	First Stage: Study Treatment n=8 participants at risk Visilizumab, Tacrolimus and Methotrexate. All participants.
Skin and subcutaneous tissue disorders Rash/desquamation	12.5% 1/8 • 5 years The time of administration of visilizumab on Day 1 through Day 360. Per protocol, expected transplant/GVHD-related (other than serious) adverse event details were not tabulated in the same manner as serious adverse events.
Gastrointestinal disorders Hemorrhage, GI - Colon	25.0% 2/8 • 5 years The time of administration of visilizumab on Day 1 through Day 360. Per protocol, expected transplant/GVHD-related (other than serious) adverse event details were not tabulated in the same manner as serious adverse events.
Gastrointestinal disorders Diarrhea	12.5% 1/8 • 5 years The time of administration of visilizumab on Day 1 through Day 360. Per protocol, expected transplant/GVHD-related (other than serious) adverse event details were not tabulated in the same manner as serious adverse events.
Infections and infestations Febrile neutropenia	25.0% 2/8 • 5 years The time of administration of visilizumab on Day 1 through Day 360. Per protocol, expected transplant/GVHD-related (other than serious) adverse event details were not tabulated in the same manner as serious adverse events.
Infections and infestations Infection - Blood	12.5% 1/8 • 5 years The time of administration of visilizumab on Day 1 through Day 360. Per protocol, expected transplant/GVHD-related (other than serious) adverse event details were not tabulated in the same manner as serious adverse events.
Infections and infestations Infection - Bronchus	12.5% 1/8 • 5 years The time of administration of visilizumab on Day 1 through Day 360. Per protocol, expected transplant/GVHD-related (other than serious) adverse event details were not tabulated in the same manner as serious adverse events.
Respiratory, thoracic and mediastinal disorders Adult Respiratory Distress Syndrome (ARDS)	12.5% 1/8 • 5 years The time of administration of visilizumab on Day 1 through Day 360. Per protocol, expected transplant/GVHD-related (other than serious) adverse event details were not tabulated in the same manner as serious adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	12.5% 1/8 • 5 years The time of administration of visilizumab on Day 1 through Day 360. Per protocol, expected transplant/GVHD-related (other than serious) adverse event details were not tabulated in the same manner as serious adverse events.
Respiratory, thoracic and mediastinal disorders Pneumonitis/pulmonary infiltrates	12.5% 1/8 • 5 years The time of administration of visilizumab on Day 1 through Day 360. Per protocol, expected transplant/GVHD-related (other than serious) adverse event details were not tabulated in the same manner as serious adverse events.
Respiratory, thoracic and mediastinal disorders Pulmonary/Upper Respiratory - Other - pseudomonas pneumonia	12.5% 1/8 • 5 years The time of administration of visilizumab on Day 1 through Day 360. Per protocol, expected transplant/GVHD-related (other than serious) adverse event details were not tabulated in the same manner as serious adverse events.

Other adverse events

Adverse event data not reported

Additional Information

Lia Perez, M.D.

H. Lee Moffitt Cancer Center and Research Institute

Phone: 813-745-7202

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place