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

NCT ID: NCT00720629

Last Updated: 2014-07-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-31
• Study Completion Date: 2013-12-31

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".

Conditions

Graft Versus Host Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

First Study Stage: Study Treatment

Visilizumab, Tacrolimus and Methotrexate.

Group Type: EXPERIMENTAL

Visilizumab

Intervention Type: DRUG

3 mg/m\^3, IV (in the vein) on day 0, prior to hematopoietic cell infusion (transplant).

Tacrolimus

Intervention Type: DRUG

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.

Methotrexate

Intervention Type: DRUG

15 mg/m\^2 intravenously (IV) on Day 1 after transplant; 10 mg/m\^2 IV on Days 3, 6 and 11 after transplant.

Second Study Stage: Standard Treatment

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.

Group Type: ACTIVE_COMPARATOR

Antithymocyte globulin (ATG)

Intervention Type: DRUG

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.

Tacrolimus

Intervention Type: DRUG

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.

Methotrexate

Intervention Type: DRUG

15 mg/m\^2 IV on Day 1 after transplant; 10 mg/m\^2 IV on Days 3, 6 and 11 after transplant.

Interventions

Visilizumab

3 mg/m\^3, IV (in the vein) on day 0, prior to hematopoietic cell infusion (transplant).

Intervention Type: DRUG

Tacrolimus

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.

Intervention Type: DRUG

Methotrexate

15 mg/m\^2 intravenously (IV) on Day 1 after transplant; 10 mg/m\^2 IV on Days 3, 6 and 11 after transplant.

Intervention Type: DRUG

Antithymocyte globulin (ATG)

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.

Intervention Type: DRUG

Tacrolimus

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.

Intervention Type: DRUG

Methotrexate

15 mg/m\^2 IV on Day 1 after transplant; 10 mg/m\^2 IV on Days 3, 6 and 11 after transplant.

Intervention Type: DRUG

Other Intervention Names

Thymoglobulin-ATG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lia Perez, MD

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Locations

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 21874061 (View on PubMed)

Related Links

http://www.moffitt.org/

H. Lee Moffitt Cancer Center \& Research Institute

Other Identifiers

R01CA132197-06A2

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MCC-15033

Identifier Type: -

Identifier Source: org_study_id