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

NCT00720629 | Terminated Phase 2 Results DMC

• 2 other identifiers: MCC-15033R01CA132197-06A2
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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".

Conditions

Graft Versus Host Disease

Keywords

graft versus host disease; GVHD; allogeneic transplant; GVHD prevention; unrelated donors; mismatched unrelated donors; hematological malignancies; Leukemia; Lymphoma; Myelodysplastic Syndrome; Myelofibrosis; Aplastic Anemia; Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

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

  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

  100 days

Secondary Outcomes (5)

• Incidence of Epstein-Barr Virus (EBV) Reactivation

  3 months

• Incidence of Rituximab Response to Reactivated EBV Without PTLD

  100 days

• Overall Survival (OS)

  At 2 years and 5 years

• Pharmacodynamics of Visilizumab - Test 1

  At 1 - 2 hours

• Pharmacodynamics of Visilizumab - Test 2

  Up to 205 hours

Study Arms (2)

First Study Stage: Study Treatment

EXPERIMENTAL

Visilizumab, Tacrolimus and Methotrexate.

Drug: Visilizumab; Drug: Tacrolimus; Drug: Methotrexate

Second Study Stage: Standard Treatment

ACTIVE COMPARATOR

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.

Drug: Antithymocyte globulin (ATG); Drug: Tacrolimus; Drug: Methotrexate

Interventions

Visilizumab DRUG

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

First Study Stage: Study Treatment

Tacrolimus 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.

First Study Stage: Study Treatment

Methotrexate 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.

First Study Stage: Study Treatment

Antithymocyte globulin (ATG) 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.

Also known as: Thymoglobulin-ATG

Second Study Stage: Standard Treatment

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Related Publications (1)

• 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 DERIVED

Related Links

• H. Lee Moffitt Cancer Center \& Research Institute

MeSH Terms

Conditions

Graft vs Host Disease; Hematologic Neoplasms; Leukemia; Lymphoma; Myelodysplastic Syndromes; Primary Myelofibrosis; Anemia, Aplastic; Multiple Myeloma

Interventions

visilizumab; Tacrolimus; Methotrexate; Antilymphocyte Serum; thymoglobulin

Condition Hierarchy (Ancestors)

Immune System Diseases; Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Bone Marrow Diseases; Myeloproliferative Disorders; Anemia; Bone Marrow Failure Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Limitations and Caveats

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.

Results Point of Contact

• Title: Lia Perez, M.D.
• Organization: H. Lee Moffitt Cancer Center and Research Institute

lia.perez@moffitt.org

813-745-7202

Study Officials

• Lia Perez, MD

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2008
• First Posted: July 23, 2008
• Study Start: December 1, 2007
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: July 18, 2014
• Results First Posted: July 4, 2014

Record last verified: 2014-04

Locations

US (1)