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Sirolimus as Secondary Therapy in Chronic Graft-Versus-Host Disease Not Responding To Prior Treatment

23 mai 2017 mis à jour par: Paul Carpenter, Fred Hutchinson Cancer Center

A Phase II Clinical Trial to Evaluate the Safety and Efficacy of Sirolimus for Secondary Treatment of Chronic Graft-versus-Host Disease

This phase II trial studies the side effects and how well sirolimus works as secondary therapy in treating patients with chronic graft-versus-host disease (GVHD) that did not respond to prior treatment. Sirolimus may be an effective treatment for chronic GVHD

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

PRIMARY OBJECTIVES:

I. To assess the safety of sirolimus administered at a dose which provides steady-state, whole blood trough levels of 5-10 ng/mL in patients with chronic GVHD.

II. To determine whether administration of sirolimus provides benefit for patients with chronic GVHD that has not responded adequately to previous systemic treatment.

OUTLINE:

Patients receive sirolimus orally (PO) once daily (QD). Patients continue to receive prednisone and cyclosporine or tacrolimus at the discretion of the managing physician.

After completion of study treatment, patients are followed up periodically.

Type d'étude

Interventionnel

Inscription (Réel)

44

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • États-Unis
    • Washington
      • Seattle, Washington, États-Unis, 98109
        • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Enfant
  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  • Biopsy-confirmed diagnosis of clinical extensive chronic GVHD with inadequate response to previous treatment and where secondary systemic therapy is indicated because of

    • Clinical progression of signs and symptoms of chronic GVHD in a previously involved organ, or
    • Development of signs and symptoms of chronic GVHD in a previously uninvolved organ, or
    • Absence of improvement after 3 months of primary treatment, or
    • Continued need for treatment with prednisone at doses >= 1.0 mg/kg/day for more than 2 months, without qualification for type of donor, graft or conditioning regimen
  • Patient or guardian able and willing to provide informed consent
  • Stated willingness to use contraception in women of child-bearing potential (Food and Drug Administration [FDA] requirement)
  • Stated willingness of the patient to comply with study procedures and reporting requirements
  • Stated willingness of the physician most involved in management of chronic GVHD (the "managing physician,") to comply with study procedures and reporting requirements

Exclusion Criteria:

  • Fungal or viral infection with no radiographic evidence of improvement during continued appropriate antimicrobial therapy
  • Cytomegalovirus (CMV) antigenemia unresponsive to antiviral therapy
  • Active disseminated varicella zoster virus (VZV) infection with persistent non-crusted lesions
  • Inability to tolerate oral medications
  • Absolute neutrophil count (ANC) < 1500/uL
  • Platelet count < 50,000/uL
  • Persistent or recurrent malignancy, including histopathologic evidence of myeloma or lymphoma; patients with breakpoint cluster region-abelson (bcr/abl) detected by polymerase chain reaction (PCR) assay as the only evidence of persistent chronic myeloid leukemia may be enrolled
  • Pregnancy
  • Known history of hypersensitivity to sirolimus

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Soins de soutien
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Sirolimus
Study participants receive sirolimus added once daily to their baseline combination therapy of prednisone plus either cyclosporine or tacrolimus at the discretion of the managing physician. Treatment other than cyclosporine (or tacrolimus) and prednisone must be discontinued when administration of sirolimus is started. Topical therapy, including psoralen and UVA irradiation (PUVA), glucocorticoid creams, topical tacrolimus, oral beclomethasone, topical azathioprine and ophthalmic glucocorticoids may be given at the discretion of the managing physician in consultation with the transplant center.
Médicament: sirolimus
Bon de commande donné
Autres noms:
  • Rapamune
  • AY 22989
  • rapamycine
  • SLM

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Number of Participants Experiencing Treatment Success
Délai: Approximately 7 years
Defined as the absence of any immunosuppressive treatment, including sirolimus, with resolution of all reversible manifestations of chronic GVHD and no additional systemic therapy.
Approximately 7 years
Number of Participants Experiencing Treatment Failure
Délai: Approximately 7 years
Defined as the initiation of additional systemic therapy, development of bronchiolitis obliterans, or death from causes other than recurrent malignancy during primary treatment for chronic GVHD, whichever occurs first.
Approximately 7 years
Number of Participants Needing Additional Systemic Therapy
Délai: Approximately 7 years
Includes any intervention intended to control chronic GVHD through an immunosuppressive effect from oral or parenteral administration of any systemic medication not originally given under auspices of this protocol.
Approximately 7 years
Number of Participants With Recurrent Malignancy
Délai: Approximately 7 years
Defined as clinical or histopathologic evidence demonstrating the presence of any malignancy considered as the indication for transplant. Recurrent malignancy will also be defined as any post-transplant intervention not routinely used to prevent the development of overt recurrence, prompted by laboratory evidence of persisting malignant cells but without clinical or histopathologic evidence of recurrence.
Approximately 7 years

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Proportion of Patients Who Discontinue Administration of Sirolimus Because of Toxicity
Délai: Approximately 7 years
Approximately 7 years
Proportion With Infections Categorized by Organism
Délai: Approximately 7 years
Approximately 7 years
Secondary Malignancies
Délai: Up to 7 years
Proportion of participants who developed at least one secondary malignancy by 7 years
Up to 7 years
Duration of Treatment With Prednisone
Délai: Approximately 7 years
Approximately 7 years
Probability of Survival Without Recurrent Malignancy
Délai: Approximately 7 years
Kaplan-Meier estimate assessed at 7 years for probability of survival without recurrent malignancy.
Approximately 7 years
Probability of Overall Survival
Délai: Approximately 7 years
Kaplan-Meier estimate assessed at 7 years
Approximately 7 years
Probability of Cumulative Incidence of Death Without Recurrent Malignancy
Délai: Approximately 7 years
Analyzed with recurrent malignancy as a competing risk factor. Assessed at 7 years.
Approximately 7 years
Probability of Cumulative Incidence of Recurrent Malignancy
Délai: Approximately 7 years
Analyzed with death as a competing risk factor. Assessed at 7 years.
Approximately 7 years

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Fred Hutchinson Cancer Center

Collaborateurs

National Cancer Institute (NCI)

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 avril 2002

Achèvement primaire (Réel)

1 juillet 2009

Achèvement de l'étude (Réel)

10 juin 2010

Dates d'inscription aux études

Première soumission

8 mars 2004

Première soumission répondant aux critères de contrôle qualité

9 mars 2004

Première publication (Estimation)

10 mars 2004

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

20 juin 2017

Dernière mise à jour soumise répondant aux critères de contrôle qualité

23 mai 2017

Dernière vérification

1 mai 2017

Plus d'information

Termes liés à cette étude

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • 1706.00
  • NCI-2011-01817 (Identificateur de registre: CTRP (Clinical Trial Reporting Program))

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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