- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT00602693
T-Regulatory Cell Infusion Post Umbilical Cord Blood Transplant in Patients With Advanced Hematologic Cancer
Phase I Study of Infusion of Umbilical Cord Blood (UCB) Derived CD25+CD4+ T-Regulatory (Treg) Cells After Nonmyeloablative Cord Blood Transplantation
RATIONALE: Giving chemotherapy, such as fludarabine and cyclophosphamide, and total-body irradiation before a donor umbilical cord blood transplant helps stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T-regulatory cells after the transplant may decrease this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. However, the donor immune system may also react against the recipient's tissues (graft-versus-host disease).
PURPOSE: This phase I trial is studying the side effects and best dose of donor T-regulatory cells after an umbilical cord blood transplant in treating patients with advanced hematologic cancer or other disorder.
Studienübersicht
Status
Bedingungen
Detaillierte Beschreibung
OBJECTIVES:
Primary
- Determine the maximum tolerated dose (MTD) of umbilical cord blood (UCB)-derived T-regulatory (Treg) cells.
Secondary
- Estimate the proportion of patients with detectable circulating Treg cells at 0, 1, 3, 7, and 14 days after infusion.
- Estimate the risk of grades II-IV and III-IV acute graft versus host disease (GVHD) at day +100 with the infusion of Treg cells.
- Estimate the proportion of patients with sustained donor engraftment.
- Estimate the proportion of patients with double chimerism at 6 months and 1 year.
- Determine the speed and cumulative incidence of neutrophil recovery by day 42 and platelet recovery by 6 months after UCB transplantation.
- Estimate the risk of chronic GVHD at 1 year.
- Estimate the probability of disease-free survival at 100 days and 1 year.
- Estimate the risk of fungal and viral infections at 1 year
- Estimate the risk of relapse at 1 year
- Characterize the pattern of immune cell recovery over 1 year
OUTLINE: This is a dose-escalation study of umbilical cord blood (UCB)-derived T-regulatory (Treg) cells. Patients receive nonmyeloablative UCB transplantation and post-transplant immunosuppression as in protocol UMN-2005LS036 (without antithymocyte globulin during conditioning regimen).
- Nonmyeloablative conditioning and UCB transplantation: Patients receive allopurinol on days -7 to day 0, fludarabine phosphate intravenously (IV) over 1 hour on days -6 to -2 and cyclophosphamide IV over 2 hours on day -6; undergo total-body irradiation (TBI) once on day -1; and undergo UCB transplantation on day 0.
- Immunosuppression therapy: Beginning on day -3 and continuing until day +100, patients receive sirolimus intravenously (IV) with 8-12 mg oral loading dose followed by a single dose of 4mg/day with a target serum concentration of 3-12 mg/mL with a taper until day +180. Patients also receive mycophenolate mofetil IV or orally every 8 hours on days -3 to +30.
- Radiation therapy: total body irradiation is administered on Day -1 of 200 cGy.
- UCB Treg cell infusion: Patients receive escalating doses of UCB-derived CD4+ CD25+ Treg cells IV on day +1 (and Day +15 for dose level 5 only) until the maximum tolerated dose is obtained.
After completion of study treatment, patients are followed at day 180, 360, and 720.
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 1
Kontakte und Standorte
Studienorte
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Minnesota
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Minneapolis, Minnesota, Vereinigte Staaten, 55455
- Masonic Cancer Center at University of Minnesota
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
Inclusion Criteria:
- Ages 18 to 75 years old
Eligible for and co-enrolled on protocol UMN-2005LS036, for treatment of any of the following advanced hematologic malignancies:
- Acute leukemias in complete remission (high risk CR1 or subsequent CR); chronic myelogenous leukemia (except refractory blast crisis); myelodysplastic syndrome with severe pancytopenia or complex cytogenetics, large-cell lymphoma, Hodgkin's lymphoma and multiple myeloma, chronic lymphocytic leukemia/small lymphocytic lymphoma, marginal zone b-cell lymphoma, follicular lymphoma, lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia may be eligible after initial therapy.
- Have three partially HLA matched umbilical cord blood (UCB) units (1-2 units for UCB transplantation per MT2005-02 and 1 unit for the Treg cell infusion.)
- Adequate organ function
Exclusion Criteria:
- Patients not exposed to highly immunosuppressive single agent or multi-agent chemotherapy within 3 months, or an ablative preparative regimen for autologous hematopoietic stem cell transplant (HCT) within 1 year.
- Pregnancy or breastfeeding
- Current active serious infection
- Evidence of human immunodeficiency virus (HIV) or known HIV positive serology
- Patients with acute leukemia in morphologic relapse/persistent disease defined as >5% blasts in a > or = 15% cellular bone marrow or any % blasts if blasts have unique morphologic markers (e.g., Auer rods) or associated cytogenetic markers that allows morphologic relapse to be distinguished are not eligible.
- Chronic myelogenous leukemia in refractory blast crisis.
- Active central nervous system malignancy.
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: UCB post-transplant Treg Cell Infusion
Includes patients with high risk malignancy receiving allopurinol, fludarabine phosphate, cyclophosphamide, sirolimus, total body irradiation, double umbilical cord blood transplantation and Treg infusion cells after transplant.
Patients will receive differing dose levels as they are entered and assigned to determine the maximum tolerated dose.
|
Infusion of umbilical cord blood
Andere Namen:
Administration begins Day -7 through Day 0, tablet or powder prescribed on an individual basis.
Andere Namen:
40 mg/m^2 intravenously over 1 hour on Days -6, -5, -4, -3, -2
Andere Namen:
50 mg/kg intravenous over 2 hours on Day -6
Andere Namen:
200 cGy am Tag -1
Andere Namen:
Infusion of T regulatory cells on Day +1 (also Day +15 for Dose level 5 only).
Dose escalation ranges include 1, 3, 10, 30, 100, 300 1000, and 300 x 10^5 Treg/kg.
Andere Namen:
Beginning on day -3 and continuing until day +100, patients receive sirolimus intravenously (IV) with 8-12 mg oral loading dose followed by a single dose of 4mg/day with a target serum concentration of 3-12 mg/mL with a taper until day +180.
Andere Namen:
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Maximum tolerated dose
Zeitfenster: 48 Hours
|
Nine dose levels of CD4+CD25+ Treg are scheduled with the doses being 1, 3, 10, 30, 30+30, 100, 300, 1000, and 3000 x 10^5 Treg/kg recipient body weight.
The dose escalation will proceed in cohorts of one patient until the first dose limiting toxicity (DLT) is observed.
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48 Hours
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Number of patients with detectable Treg cells
Zeitfenster: Days 0, +1, +3, +7, and +14 after Treg cell infusion
|
determined by polymerase chain reaction (PCR) and flow cytometry
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Days 0, +1, +3, +7, and +14 after Treg cell infusion
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Number of Patients with grade II-IV and grade III-IV acute graft versus host disease (GVHD)
Zeitfenster: Day 100
|
Patients will be assessed weekly for GVHD between days 0 and 100 after transplantation using standard criteria.
Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level.
Incidence of grades II-IV and grades III-IV GVHD by day 100 will be monitored.
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Day 100
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Number of patients with sustained donor engraftment
Zeitfenster: Day 100
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Day 100
|
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Number of patients with double chimerism
Zeitfenster: 6 Months and 1 Year
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6 Months and 1 Year
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Incidence of neutrophil recovery after umbilical cord blood (UCB) transplantation
Zeitfenster: Day 42
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Day 42
|
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Number of Patients with Chronic Graft Versus Host Disease (GVHD)
Zeitfenster: 1 Year
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1 Year
|
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Number of Patients with disease-free survival
Zeitfenster: Day 100 and 1 Year
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Day 100 and 1 Year
|
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Number of Patients with Fungal and Viral Infections
Zeitfenster: 1 Year
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Count of reported infections.
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1 Year
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Incidence of platelet recovery after umbilical cord blood (UCB)
Zeitfenster: 6 Months After Transplant
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6 Months After Transplant
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Number of Patients with Disease Relapse
Zeitfenster: 1 Year
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1 Year
|
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Percent of Patients with Immune Cell Recovery
Zeitfenster: 1 Year
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1 Year
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Mitarbeiter und Ermittler
Ermittler
- Hauptermittler: Margaret L. MacMillan, MD, Masonic Cancer Center, University of Minnesota
- Hauptermittler: Claudio G. Brunstein, MD, PhD, Masonic Cancer Center, University of Minnesota
Publikationen und hilfreiche Links
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
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Herz-Kreislauf-Erkrankungen
- Gefäßerkrankungen
- Erkrankungen des Immunsystems
- Neubildungen nach histologischem Typ
- Neubildungen
- Lymphoproliferative Erkrankungen
- Lymphatische Erkrankungen
- Immunproliferative Erkrankungen
- Erkrankungen des Knochenmarks
- Hämatologische Erkrankungen
- Hämorrhagische Störungen
- Hämostasestörungen
- Paraproteinämien
- Bluteiweißstörungen
- Lymphom
- Myelodysplastische Syndrome
- Multiples Myelom
- Neubildungen, Plasmazelle
- Leukämie
- Plasmazytom
- Physiologische Wirkungen von Arzneimitteln
- Molekulare Mechanismen der pharmakologischen Wirkung
- Antiinfektiva
- Enzym-Inhibitoren
- Antirheumatika
- Antimetaboliten, antineoplastisch
- Antimetaboliten
- Antineoplastische Mittel
- Immunsuppressive Mittel
- Immunologische Faktoren
- Schutzmittel
- Antineoplastische Mittel, alkylierend
- Alkylierungsmittel
- Myeloablative Agonisten
- Antibakterielle Mittel
- Antibiotika, antineoplastische
- Antimykotika
- Antioxidantien
- Radikalfänger
- Gichtunterdrücker
- Cyclophosphamid
- Fludarabin
- Fludarabinphosphat
- Sirolimus
- Allopurinol
Andere Studien-ID-Nummern
- 2007LS022
- MT2006-01 (Andere Kennung: Blood and Marrow Transplantation Program)
- 0701M00303 (Andere Kennung: IRB, University of Minnesota)
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