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

10 juli 2014 bijgewerkt door: H. Lee Moffitt Cancer Center and Research Institute

A Phase II Study of Visilizumab for the Prevention of Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation

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".

Studie Overzicht

Toestand

Beëindigd

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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".

Studietype

Ingrijpend

Inschrijving (Werkelijk)

8

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Verenigde Staten
    • Florida
      • Tampa, Florida, Verenigde Staten, 33612
        • H. Lee Moffitt Cancer Center & Research Institute

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 60 jaar (Volwassen)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Preventie
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: First Study Stage: Study Treatment
Visilizumab, Tacrolimus and Methotrexate.
Geneesmiddel: Visilizumab
3 mg/m^3, IV (in the vein) on day 0, prior to hematopoietic cell infusion (transplant).
Geneesmiddel: 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.
Geneesmiddel: 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.
Geneesmiddel: 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.
Geneesmiddel: Methotrexate
15 mg/m^2 IV on Day 1 after transplant; 10 mg/m^2 IV on Days 3, 6 and 11 after transplant.
Actieve vergelijker: 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.
Geneesmiddel: 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.
Geneesmiddel: 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.
Geneesmiddel: 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.
Geneesmiddel: Methotrexate
15 mg/m^2 IV on Day 1 after transplant; 10 mg/m^2 IV on Days 3, 6 and 11 after transplant.
Geneesmiddel: 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.
Andere namen:
  • Thymoglobulin-ATG

Wat meet het onderzoek?

Primaire uitkomstmaten

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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Incidence of Epstein-Barr Virus (EBV) Reactivation
Tijdsspanne: 3 months
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.
3 months
Incidence of Rituximab Response to Reactivated EBV Without PTLD
Tijdsspanne: 100 days

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).
100 days
Overall Survival (OS)
Tijdsspanne: At 2 years and 5 years
Median OS in days. Survival was measured from the time of transplant to the time of death.
At 2 years and 5 years
Pharmacodynamics of Visilizumab - Test 1
Tijdsspanne: At 1 - 2 hours
Mean Cmax (±SD)
At 1 - 2 hours
Pharmacodynamics of Visilizumab - Test 2
Tijdsspanne: Up to 205 hours
Mean terminal half-life (±SD)
Up to 205 hours

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Medewerkers

National Cancer Institute (NCI)
National Institutes of Health (NIH)

Onderzoekers

  • Hoofdonderzoeker: Lia Perez, MD, H. Lee Moffitt Cancer Center and Research Institute

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Nuttige links

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 december 2007

Primaire voltooiing (Werkelijk)

1 december 2013

Studie voltooiing (Werkelijk)

1 december 2013

Studieregistratiedata

Eerst ingediend

21 juli 2008

Eerst ingediend dat voldeed aan de QC-criteria

21 juli 2008

Eerst geplaatst (Schatting)

23 juli 2008

Updates van studierecords

Laatste update geplaatst (Schatting)

18 juli 2014

Laatste update ingediend die voldeed aan QC-criteria

10 juli 2014

Laatst geverifieerd

1 april 2014

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • MCC-15033
  • R01CA132197-06A2 (Subsidie/contract van de Amerikaanse NIH)

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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