NCT00720629 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: TERMINATED
Registry last update: 2014-07-18

The purpose of this study was to test whether a new drug named visilizumab would decrease the severity of graft-versus-host disease in patients treated with a mismatched donor. Investigators planned to use visilizumab in combination with tacrolimus and methotrexate as the "study treatment".

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Participants With Grade II-IV Acute Graft-versus-Host Disease (GVHD) Score at 100 Days

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outcome · POSTED

Incidence of Epstein-Barr Virus (EBV) Reactivation

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outcome · POSTED

Incidence of Rituximab Response to Reactivated EBV Without PTLD

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Pharmacodynamics of Visilizumab - Test 1

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outcome · POSTED

Pharmacodynamics of Visilizumab - Test 2

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * One of the following diagnoses with histological confirmation by the Pathology Department at H. Lee Moffitt Cancer Center: * Acute Lymphocytic Leukemia (ALL) in complete remission 1 (CR1) with t(9:22) or t(4:11), or any ALL beyond CR1 * Acute Myelogenous Leukemia (AML) with high risk cytogenetics in CR1 as defined by Bloomfield any AML beyond CR1 * Myelodysplastic Syndrome (MDS) with International Prognostic Scoring System (IPSS) score \> 1 * Chronic myelomonocytic leukemia (CMML) * Chronic Myelogenous Leukemia (CML) with Imatinib-refractory chronic phase, or beyond chronic phase by morphology or cytogenetics * Myelofibrosis * Severe aplastic anemia * Chemosensitive Non-Hodgkin's lymphoma and Hodgkin's disease that are not candidate to autologous transplant due to prior autologous transplantation * Multiple Myeloma patient not candidate for autologous stem cell transplantation * Karnofsky performance status ≥ 70% (adult) * Normal organ and marrow function as defined below: * Hepatic: Total bilirubin must be less than or equal to 2mg/dL (Gilbert and other syndromes with increased indirect bilirubin are allowed); serum transaminases must be less than two times the upper limit of normal * Pulmonary: diffusing capacity of lung for carbon monoxide (DLCO) (corrected for Hgb), forced expiratory volume-one second (FEV1), forced vital capacity (FVC) must be greater than 50% predicted * Cardiac: Left ventricular ejection fraction at rest must be greater than 50% * Renal: Creatinine clearance (measured or calculated) must be equal or greater than 50 ml/min/1.73m\^2 Exclusion Criteria: * Anti thymocyte globulin (ATG) or anti T cell therapy in prior 45 days * Splenectomized patients; * A positive pregnancy test administered to all females of childbearing potential prior to allogeneic stem cell transplant * Inability to comply with follow up as determined by the patient's physician * HIV-I/II infection prior to hematopoietic stem cell (HSC) transplantation, confirmed by nucleic acid test (NAT) * Uncontrolled bacterial or fungal infection * History of documented invasive aspergillosis or cytomegalovirus (CMV) pneumonia * Presence of any of the following comorbid conditions: * History of myocardial infarction * Congestive heart failure (even if symptomatically controlled) * Peripheral vascular disease (including intermittent claudication or history of bypass for arterial insufficiency) * Untreated thoracic or abdominal aneurysm (6cm or more) * History of any cerebrovascular accident including transient ischemic attacks * Dementia * History of peptic ulcer disease requiring treatment * Connective tissue/rheumatologic disorders * Diabetes unless being managed with dietary changes only * Hemiplegia/paraplegia * History of solid tumor excluding skin or cervical carcinoma after curative resection
healthy Volunteers: false
maximum Age: 60 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT

Treatment arms and interventions

arm Groups

description
Visilizumab, Tacrolimus and Methotrexate.
intervention Names
Drug: Visilizumab
Drug: Tacrolimus
Drug: Methotrexate
label
First Study Stage: Study Treatment
type
EXPERIMENTAL
description
Second Stage: Antithymocyte-globulin (ATG), Tacrolimus and Methotrexate. The study was closed during first stage and did not proceed to the second stage comparison to ATG in combination with tacrolimus/methotrexate as originally planned.
intervention Names
Drug: Antithymocyte globulin (ATG)
Drug: Tacrolimus
Drug: Methotrexate
label
Second Study Stage: Standard Treatment
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
First Study Stage: Study Treatment
description
3 mg/m\^3, IV (in the vein) on day 0, prior to hematopoietic cell infusion (transplant).
name
Visilizumab
type
DRUG
arm Group Labels
First Study Stage: Study Treatment
description
0.02 mg/kg/24h (based on ideal body weight) continuous infusion (over 24 hours) beginning on day 4 after transplant up to approximately day 180 after transplant. Switch to oral tacrolimus as able. Dose adjusted based on levels. In the absence of GVHD, the dose to be tapered beginning 100 days after transplant.
name
Tacrolimus
type
DRUG
arm Group Labels
First Study Stage: Study Treatment
description
15 mg/m\^2 intravenously (IV) on Day 1 after transplant; 10 mg/m\^2 IV on Days 3, 6 and 11 after transplant.
name
Methotrexate
type
DRUG
arm Group Labels
Second Study Stage: Standard Treatment
description
1 mg/kg IV over 6 hours on Day 3 before transplant; 3.25 mg/kg IV over 4 hours on days 2 and 1 before transplant.
name
Antithymocyte globulin (ATG)
other Names
Thymoglobulin-ATG
type
DRUG
arm Group Labels
Second Study Stage: Standard Treatment
description
0.03 mg/kg/24h (based on ideal body weight) continuous infusion (over 24 hours) beginning on day 3 before transplant up to approximately day 180 after transplant. Switch to oral tacrolimus as able. Dose adjusted based on levels. In the absence of GVHD, the dose to be tapered beginning 100 days after transplant.
name
Tacrolimus
type
DRUG
arm Group Labels
Second Study Stage: Standard Treatment
description
15 mg/m\^2 IV on Day 1 after transplant; 10 mg/m\^2 IV on Days 3, 6 and 11 after transplant.
name
Methotrexate
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

PREVENTION

Enrollment

count: 8
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

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
measure
Number of Participants With Grade II-IV Acute Graft-versus-Host Disease (GVHD) Score at 100 Days
time Frame
100 days

secondary Outcomes

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.
measure
Incidence of Epstein-Barr Virus (EBV) Reactivation
time Frame
3 months
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).
measure
Incidence of Rituximab Response to Reactivated EBV Without PTLD
time Frame
100 days
description
Median OS in days. Survival was measured from the time of transplant to the time of death.
measure
Overall Survival (OS)
time Frame
At 2 years and 5 years
description
Mean Cmax (±SD)
measure
Pharmacodynamics of Visilizumab - Test 1
time Frame
At 1 - 2 hours
description
Mean terminal half-life (±SD)
measure
Pharmacodynamics of Visilizumab - Test 2
time Frame
Up to 205 hours

Full study description

brief Summary: The purpose of this study was to test whether a new drug named visilizumab would decrease the severity of graft-versus-host disease in patients treated with a mismatched donor. Investigators planned to use visilizumab in combination with tacrolimus and methotrexate as the "study treatment".
detailed Description: The protocol plan was a two stage, controlled, phase II study to assess safety and compare the grade of acute graft-versus-host disease (GVHD) with visilizumab, or Anti-thymocyte Globulin (ATG) in combination with tacrolimus + methotrexate in patients at high risk of GVHD after transplant from unrelated donors mismatched for 1-2 alleles of any type at human leukocyte antigen (HLA) A, B, C and DRB1. The study design included two stages. The first stage of the trial was to enroll 15 patients on a single arm to be treated with "study treatment" (visilizumab, tacrolimus and methotrexate) to assess for treatment safety and exclude intolerable GVHD. The second stage of the trial was to include a random control group of patients treated with the current "standard treatment" (ATG, tacrolimus, and methotrexate) or "study treatment". The purpose of this comparison was to determine if the "study treatment" visilizumab causes less severe side effects and if it is more potent in reducing graft-versus-host disease symptoms than the "standard treatment".

Source references

references

citation
Pidala J, Perez L, Beato F, Anasetti C. Ustekinumab demonstrates activity in glucocorticoid-refractory acute GVHD. Bone Marrow Transplant. 2012 May;47(5):747-8. doi: 10.1038/bmt.2011.172. Epub 2011 Aug 29. No abstract available.
pmid
21874061
type
DERIVED