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

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ClinicalTrials.gov Identifier: NCT00720629
Recruitment Status : Terminated
First Posted : July 23, 2008
Results First Posted : July 4, 2014
Last Update Posted : July 18, 2014
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Condition Graft Versus Host Disease
Interventions Drug: Visilizumab
Drug: Tacrolimus
Drug: Methotrexate
Drug: Antithymocyte globulin (ATG)
Enrollment 8
Recruitment Details Participants were enrolled at Moffitt Cancer Center between February 2008 and April 2010.
Pre-assignment Details 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.
Arm/Group Title First Study Stage: Study Treatment
Hide Arm/Group Description Visilizumab, Tacrolimus and Methotrexate. All participants.
Period Title: Overall Study
Started 8
Completed 8
Not Completed 0
Arm/Group Title First Stage: Study Treatment
Hide Arm/Group Description Visilizumab, Tacrolimus and Methotrexate. All participants.
Overall Number of Baseline Participants 8
Hide Baseline Analysis Population Description
First Stage: Study Treatment. All participants.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 8 participants
36.5
(23 to 50)
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants
<=18 years
0
   0.0%
Between 18 and 65 years
8
 100.0%
>=65 years
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants
Female
6
  75.0%
Male
2
  25.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 8 participants
8
1.Primary Outcome
Title Number of Participants With Grade II-IV Acute Graft-versus-Host Disease (GVHD) Score at 100 Days
Hide Description

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

Time Frame 100 days
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Hide Analysis Population Description
All participants
Arm/Group Title First Study Stage: Study Treatment
Hide Arm/Group Description:
Visilizumab, Tacrolimus and Methotrexate. All participants.
Overall Number of Participants Analyzed 8
Measure Type: Number
Unit of Measure: participants
Grade II-IV Acute GVHD 8
Grade I-II Acute GVHD 6
Grade III-IV Acute GVHD 2
2.Secondary Outcome
Title Incidence of Epstein-Barr Virus (EBV) Reactivation
Hide Description 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.
Time Frame 3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants
Arm/Group Title First Study Stage: Study Treatment
Hide Arm/Group Description:
Visilizumab, Tacrolimus and Methotrexate. All participants.
Overall Number of Participants Analyzed 8
Measure Type: Number
Unit of Measure: participants
6
3.Secondary Outcome
Title Incidence of Rituximab Response to Reactivated EBV Without PTLD
Hide Description

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).

Time Frame 100 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Reactivated EBV participants
Arm/Group Title First Study Stage: Study Treatment
Hide Arm/Group Description:
Visilizumab, Tacrolimus and Methotrexate. All participants.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: participants
6
4.Secondary Outcome
Title Overall Survival (OS)
Hide Description Median OS in days. Survival was measured from the time of transplant to the time of death.
Time Frame At 2 years and 5 years
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Hide Analysis Population Description
Participants who had died by Year 2 and additional participants who had died by Year 5.
Arm/Group Title 2 Year Analysis Group 5 Year Analysis Group
Hide Arm/Group Description:
First Study Stage: Study Treatment. Visilizumab, Tacrolimus and Methotrexate.
First Study Stage: Study Treatment. Visilizumab, Tacrolimus and Methotrexate.
Overall Number of Participants Analyzed 6 2
Median (Full Range)
Unit of Measure: days
197
(150 to 643)
1803
(1791 to 1816)
5.Secondary Outcome
Title Pharmacodynamics of Visilizumab - Test 1
Hide Description Mean Cmax (±SD)
Time Frame At 1 - 2 hours
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants
Arm/Group Title First Study Stage: Study Treatment
Hide Arm/Group Description:
Visilizumab, Tacrolimus and Methotrexate. All participants.
Overall Number of Participants Analyzed 8
Mean (Standard Deviation)
Unit of Measure: ng/mL
1564  (428)
6.Secondary Outcome
Title Pharmacodynamics of Visilizumab - Test 2
Hide Description Mean terminal half-life (±SD)
Time Frame Up to 205 hours
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Hide Analysis Population Description
All participants
Arm/Group Title First Study Stage: Study Treatment
Hide Arm/Group Description:
Visilizumab, Tacrolimus and Methotrexate. All participants.
Overall Number of Participants Analyzed 8
Mean (Standard Deviation)
Unit of Measure: hours
157  (48)
Time Frame 5 years
Adverse Event Reporting Description 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.
 
Arm/Group Title First Stage: Study Treatment
Hide Arm/Group Description Visilizumab, Tacrolimus and Methotrexate. All participants.
All-Cause Mortality
First Stage: Study Treatment
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
First Stage: Study Treatment
Affected / at Risk (%)
Total   8/8 (100.00%) 
Gastrointestinal disorders   
Hemorrhage, GI - Colon  1  2/8 (25.00%) 
Diarrhea  1  1/8 (12.50%) 
Infections and infestations   
Febrile neutropenia  1  2/8 (25.00%) 
Infection - Blood  1  1/8 (12.50%) 
Infection - Bronchus  1  1/8 (12.50%) 
Respiratory, thoracic and mediastinal disorders   
Adult Respiratory Distress Syndrome (ARDS)  1  1/8 (12.50%) 
Dyspnea (shortness of breath)  1  1/8 (12.50%) 
Pneumonitis/pulmonary infiltrates  1  1/8 (12.50%) 
Pulmonary/Upper Respiratory - Other - pseudomonas pneumonia  1  1/8 (12.50%) 
Skin and subcutaneous tissue disorders   
Rash/desquamation  1  1/8 (12.50%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
First Stage: Study Treatment
Affected / at Risk (%)
Total   0/8 (0.00%) 
Study closed early during the first stage, did not proceed to the second stage comparison as planned. Investigators exercised right to close the study prematurely for lack of efficacy, although no protocol-defined end points had been met.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Lia Perez, M.D.
Organization: H. Lee Moffitt Cancer Center and Research Institute
Phone: 813-745-7202
Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00720629     History of Changes
Other Study ID Numbers: MCC-15033
R01CA132197-06A2 ( U.S. NIH Grant/Contract )
First Submitted: July 21, 2008
First Posted: July 23, 2008
Results First Submitted: May 1, 2014
Results First Posted: July 4, 2014
Last Update Posted: July 18, 2014