Sirolimus as Secondary Therapy in Chronic Graft-Versus-Host Disease Not Responding To Prior Treatment
23. Mai 2017 aktualisiert von: 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
Studienübersicht
Status
Abgeschlossen
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
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.
Studientyp
Interventionell
Einschreibung (Tatsächlich)
44
Phase
- Phase 2
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienorte
-
-
Washington
-
Seattle, Washington, Vereinigte Staaten, 98109
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
-
-
Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
- Kind
- Erwachsene
- Älterer Erwachsener
Akzeptiert gesunde Freiwillige
Nein
Studienberechtigte Geschlechter
Alle
Beschreibung
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
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Unterstützende Pflege
- Zuteilung: N / A
- Interventionsmodell: Einzelgruppenzuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
|
Experimental: 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.
|
PO gegeben
Andere Namen:
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Number of Participants Experiencing Treatment Success
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Proportion of Patients Who Discontinue Administration of Sirolimus Because of Toxicity
Zeitfenster: Approximately 7 years
|
Approximately 7 years
|
|
|
Proportion With Infections Categorized by Organism
Zeitfenster: Approximately 7 years
|
Approximately 7 years
|
|
|
Secondary Malignancies
Zeitfenster: 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
Zeitfenster: Approximately 7 years
|
Approximately 7 years
|
|
|
Probability of Survival Without Recurrent Malignancy
Zeitfenster: Approximately 7 years
|
Kaplan-Meier estimate assessed at 7 years for probability of survival without recurrent malignancy.
|
Approximately 7 years
|
|
Probability of Overall Survival
Zeitfenster: Approximately 7 years
|
Kaplan-Meier estimate assessed at 7 years
|
Approximately 7 years
|
|
Probability of Cumulative Incidence of Death Without Recurrent Malignancy
Zeitfenster: 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
Zeitfenster: Approximately 7 years
|
Analyzed with death as a competing risk factor.
Assessed at 7 years.
|
Approximately 7 years
|
Mitarbeiter und Ermittler
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Sponsor
Mitarbeiter
Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn
1. April 2002
Primärer Abschluss (Tatsächlich)
1. Juli 2009
Studienabschluss (Tatsächlich)
10. Juni 2010
Studienanmeldedaten
Zuerst eingereicht
8. März 2004
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
9. März 2004
Zuerst gepostet (Schätzen)
10. März 2004
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
20. Juni 2017
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
23. Mai 2017
Zuletzt verifiziert
1. Mai 2017
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- 1706.00
- NCI-2011-01817 (Registrierungskennung: CTRP (Clinical Trial Reporting Program))
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