- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT01785810
Phase II Maraviroc for GVHD Prevention
A Phase II Study to Assess the Efficacy of Maraviroc in Prophylaxis of GVHD in Patients With Hematologic Malignancies Undergoing Reduced-Intensity Allogeneic SCT From Unrelated Donors
RATIONALE: Successful allogeneic stem-cell transplantation is often limited by graft-versus-host disease (GVHD). Migration of donor cells into tissues plays a major role in GVHD. Drugs that block chemokine receptors such as CCR5, can potentially decrease the migration of donor cells into tissues. Blocking CCR5 after allogeneic stem-cell transplantation may therefore reduce the rates of GVHD.
PURPOSE: This study explores the efficacy of pharmacologic inhibition of CCR5 in prevention of GVHDby administering maraviroc during allogeneic stem-cell transplantation with reduced intensity conditioning.
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
Detailed Description:
PRIMARY OBJECTIVES:
To estimate the cumulative incidence of grade 2-4 acute GVHD by day 180 with the addition of maraviroc to a standard prophylaxis regimen in patients with hematologic malignancies undergoing reduced intensity allogeneic stem-cell transplantation (RIC SCT) from unrelated donors.
SECONDARY OBJECTIVES:
- To assess the toxicity of a prolonged administration of maraviroc in patients undergoing RIC SCT.
- To estimate the rates of severe (grade 3-4) acute GVHD by day 100 and 180, grade 2-4 acute GVHD by day 100, organ-specific acute GVHD, chronic GVHD, relapse, infections, non-relapse mortality, use of immunosuppressive therapies and 1-year survival in patients treated with maraviroc after RIC SCT.
- To assess the effect of treatment with maraviroc on immune recovery, engraftment and donor T-cell chimerism in peripheral blood and in target organs.
- To assess the effect of donor and recipient CCR5 genotype on the incidence of acute GVHD in patients receiving maraviroc as part of a GVHD prophylaxis regimen.
OUTLINE: Patients receive a standard conditioning regimen with fludarabine and busulfan followed by a peripheral blood stem cell infusion from an unrelated donor, standard GVHD prophylaxis and standard antiviral and antifungal prophylaxis. In addition, all patients receive maraviroc from day -3 to d+ 90.
Patients are followed for 1 year after the stem-cell infusion.
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 2
Kontakte und Standorte
Studienorte
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Pennsylvania
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Philadelphia, Pennsylvania, Vereinigte Staaten, 19104
- Abramson Cancer Center of the University of Pennsylvania
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
Inclusion Criteria:
Patients ≥18 years of age with a hematologic malignancy other than aplastic anemia or primary myelofibrosis, scheduled to undergo RIC allogeneic SCT with a peripheral blood stem cell graft from an unrelated donor, using Flu/Bu conditioning and Tac/MTX GVHD prophylaxis. The following diagnoses are included:
- Acute leukemia - AML, ALL or acute biphenotypic leukemia. Patients will have documentation of complete remission within 6 weeks prior to their transplant. Complete remission is defined as <5% blasts on a bone marrow biopsy and absence of any known extramedullary disease.
- Chronic myelogenous leukemia in any stage, but with documentation of <5% blasts on a bone marrow biopsy within 6 weeks prior to transplant.
- Myelodysplastic syndrome of any subtype, but with documentation of <5% blasts on a bone marrow biopsy within 6 weeks prior to transplant.
- Myeloproliferative disorders other than primary myelofibrosis.
- Lymphoma - All types of lymphoma are eligible.
- CLL and PLL.
Patients who meet institutional eligibility criteria for allogeneic SCT:
- Renal function: Serum creatinine ≤2.
- Hepatic function: Baseline direct bilirubin, ALT or AST lower than three times the upper limit of normal.
- Pulmonary disease: FVC or FEV1 ≥ 40% predicted.
- Cardiac ejection fraction ≥ 40%.
- Availability of an unrelated donor, identified and screened by the NMDP. The donor will have at least 7/8 HLA-A, -B, -C and -DRB1 matching by high resolution molecular typing and will meet NMDP eligibility criteria to serve as a peripheral blood stem-cell donor.
- Karnofsky score ≥ 70% at the time of screening.
- Capacity to understand and sign the study informed consent form.
Negative pregnancy test. Women of childbearing potential (not having had a hysterectomy, a bilateral oophorectomy or bilateral tubal ligation, or be post-menopausal with a total cessation of menses of > 1 year) must agree to use documented reliable method(s) of contraception. Men should agree to use condoms during the study period.
- Co-enrollment in other clinical trials that do not include experimental GVHD therapies is allowed.
Exclusion Criteria
- Patients with aplastic anemia or primary myelofibrosis. Patients with marrow fibrosis secondary to MDS, AML or a myeloproliferative disorder other than primary myelofibrosis are eligible.
- Patients who are not expected to be available for follow-up in our institution for at least 180 days after the transplant.
- Prior allogeneic SCT.
- Uncontrolled bacterial, viral or fungal infections.
- Patients who receive maraviroc for the treatment of HIV infection.
- Patients receiving other investigational drugs for GVHD.
- Co-enrollment in other clinical trials that do not include experimental GVHD therapies is allowed.
- Patients with prior malignancies are excluded unless treated with curative intent and known to be free of disease for at least 2 years.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: N / A
- Interventionsmodell: Einzelgruppenzuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
|
Experimental: Maraviroc
Phase II, single arm, single center trial, assessing the efficacy of the combination of tacrolimus, methotrexate and maraviroc as graft-versus-host disease (GVHD) prophylaxis after unrelated donor peripheral blood stem-cell transplantation in patients with hematologic malignancies.
Patients enrolled on this trial will receive a standard conditioning regimen with fludarabine and busulfan followed by a peripheral blood stem cell infusion from an unrelated donor, standard GVHD prophylaxis and standard antiviral and antifungal prophylaxis.
In addition, all patients will receive maraviroc from day -3 to d+ 90.
|
Patients enrolled on this trial will receive a standard conditioning regimen with fludarabine and busulfan followed by a peripheral blood stem cell infusion from an unrelated donor, standard GVHD prophylaxis and standard antiviral and antifungal prophylaxis.
In addition, all patients will receive maraviroc from day -3 to d+ 90.
Andere Namen:
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Day +180 Rate of Grade II-IV Acute GVHD
Zeitfenster: 180 days
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The cumulative incidence of grade II-IV acute GVHD by day 180 after the stem-cell infusion.
This is based on consensus conference criteria.
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180 days
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Mitarbeiter und Ermittler
Ermittler
- Hauptermittler: David Porter, MD, Abramson Cancer Center of the University of Pennsylvania
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
- Neubildungen nach Standort
- Hämatologische Erkrankungen
- Neubildungen
- Hämatologische Neubildungen
- Molekulare Mechanismen der pharmakologischen Wirkung
- Antiinfektiva
- Antivirale Mittel
- Anti-HIV-Agenten
- Antiretrovirale Mittel
- HIV-Fusionsinhibitoren
- Virale Fusionsprotein-Inhibitoren
- CCR5-Rezeptorantagonisten
- Maraviroc
Andere Studien-ID-Nummern
- UPCC 04712
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