- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT00118352
Alemtuzumab, Fludarabine Phosphate, and Total-Body Irradiation Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer
Campath (Alemtuzumab) Dose Escalation, Low-Dose TBI and Fludarabine Followed by HLA Class II Mismatched Donor Stem Cell Transplantation for Patients With Hematologic Malignancies: A Multicenter Trial
Studienübersicht
Status
Bedingungen
- Chronische myelomonozytäre Leukämie
- Wiederkehrende akute myeloische Leukämie bei Erwachsenen
- Juvenile myelomonozytäre Leukämie
- Extranodales B-Zell-Lymphom der Randzone von Schleimhaut-assoziiertem lymphatischem Gewebe
- Nodales Marginalzonen-B-Zell-Lymphom
- Rezidivierendes Burkitt-Lymphom bei Erwachsenen
- Wiederkehrendes diffuses großzelliges Lymphom bei Erwachsenen
- Rezidivierendes diffuses gemischtzelliges Lymphom bei Erwachsenen
- Rezidivierendes diffuses kleinzelliges Lymphom bei Erwachsenen
- Rezidivierendes erwachsenes immunoblastisches großzelliges Lymphom
- Rezidivierendes lymphoblastisches Lymphom bei Erwachsenen
- Rezidivierendes follikuläres Lymphom Grad 1
- Rezidivierendes follikuläres Lymphom Grad 2
- Rezidivierendes follikuläres Lymphom Grad 3
- Rezidivierendes Mantelzell-Lymphom
- Rezidivierendes Marginalzonen-Lymphom
- Milz-Marginalzonen-Lymphom
- Waldenström Makroglobulinämie
- Akute myeloische Leukämie bei Erwachsenen in Remission
- Akute myeloische Leukämie im Kindesalter in Remission
- Peripheres T-Zell-Lymphom
- Anaplastisches großzelliges Lymphom
- Angioimmunoblastisches T-Zell-Lymphom
- Akute lymphoblastische Leukämie bei Erwachsenen in Remission
- Extranodales NK/T-Zell-Lymphom vom nasalen Typ bei Erwachsenen
- Akute lymphoblastische Leukämie im Kindesalter in Remission
- Chronische myeloische Leukämie im Kindesalter
- Myelodysplastische Syndrome im Kindesalter
- Chronische myeloische Leukämie in der chronischen Phase
- Kutanes B-Zell-Non-Hodgkin-Lymphom
- Hepatosplenales T-Zell-Lymphom
- Intraokulares Lymphom
- Zuvor behandelte myelodysplastische Syndrome
- Wiederkehrende akute lymphoblastische Leukämie bei Erwachsenen
- Rezidivierende lymphomatoide Granulomatose Grad III bei Erwachsenen
- Rezidivierendes Hodgkin-Lymphom bei Erwachsenen
- Rezidivierende adulte T-Zell-Leukämie/Lymphom
- Wiederkehrende akute lymphoblastische Leukämie im Kindesalter
- Wiederkehrende akute myeloische Leukämie im Kindesalter
- Wiederkehrendes kutanes T-Zell-Non-Hodgkin-Lymphom
- Rezidivierende Mycosis Fungoides/Sezary-Syndrom
- Rezidivierendes kleines lymphozytisches Lymphom
- Refraktäres multiples Myelom
- Rezidivierende chronische myeloische Leukämie
- Sekundäre myelodysplastische Syndrome
- Dünndarm-Lymphom
- Hodenlymphom
- Refraktäre chronische lymphatische Leukämie
- Refraktäre Haarzell-Leukämie
- Akute undifferenzierte Leukämie
- Atypische chronische myeloische Leukämie, BCR-ABL1 negativ
- Mastzellleukämie
- Myelodysplastische/myeloproliferative Neubildung, nicht klassifizierbar
- Diffuses großzelliges Lymphom im Kindesalter
- Immunoblastisches großzelliges Lymphom im Kindesalter
- Extranodales NK/T-Zell-Lymphom des kindlichen nasalen Typs
- Rezidivierendes anaplastisches großzelliges Lymphom im Kindesalter
- Wiederkehrende kindliche lymphomatoide Granulomatose Grad III
- Rezidivierendes großzelliges Lymphom im Kindesalter
- Rezidivierendes kindliches lymphoblastisches Lymphom
- Rezidivierendes kleinzelliges Lymphom im Kindesalter
- Rezidivierendes/refraktäres Hodgkin-Lymphom im Kindesalter
- Burkitt-Lymphom im Kindesalter
- Nichtkutanes extranodales Lymphom
Intervention / Behandlung
- Sonstiges: Labor-Biomarker-Analyse
- Arzneimittel: Fludarabinphosphat
- Verfahren: Transplantation peripherer Blutstammzellen
- Arzneimittel: Mycophenolatmofetil
- Biologisch: Alemtuzumab
- Strahlung: Ganzkörperbestrahlung
- Arzneimittel: Cyclosporin
- Verfahren: allogene hämatopoetische Stammzelltransplantation
- Biologisch: graft versus host disease prophylaxis/therapy
Detaillierte Beschreibung
PRIMARY OBJECTIVES:
I. To determine which dose of Campath (alemtuzumab) allows related and unrelated human leukocyte antigen (HLA) class-II mismatched hematopoietic cell transplantation (HCT) with an incidence of grade III-IV acute graft-versus-host disease (GVHD) less than 40%.
SECONDARY OBJECTIVES:
I. Incidence of graft rejection.
II. Number of days of steroids >= 1mg/kg required before day 100 in each patient.
III. Incidence of non-relapse mortality.
IV. Risk/incidence of infections.
V. Immune reconstitution.
VI. Risk for disease progression and relapse.
OUTLINE: This is a dose-escalation study of alemtuzumab.
NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive alemtuzumab intravenously (IV) over 6 hours once daily on days -6, -5, and -4 OR days -5 and -4 and fludarabine phosphate IV over 30 minutes on days -4, -3, and -2. Patients also undergo low-dose total-body irradiation (TBI) on day 0.
ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION (PBSCT): After completion of TBI, patients undergo allogeneic PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) or IV every 12 hours on days -3 to 180 followed by a taper until day 365 in the absence of GVHD. Beginning 4-6 hours after completion of allogeneic PBSCT, patients receive mycophenolate mofetil PO every 8 hours on days 0 to 100 followed by a taper until day 156 in the absence of GVHD.
After completion of study treatment, patients are followed up periodically for 12 months, at 18 months, and then annually for 5 years.
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 2
Kontakte und Standorte
Studienorte
-
-
-
Torino, Italien, 10126
- University of Torino
-
-
-
-
Washington
-
Seattle, Washington, Vereinigte Staaten, 98109
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
-
-
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
Inclusion Criteria:
- The patient must be not eligible for conventional transplants and must have disease expected to be stable for at least 100 days without chemotherapy
Patients with hematologic malignancies treatable with HCT will be included:
- Aggressive non-Hodgkin lymphomas (NHLs) and other histologies such as diffuse large B-cell NHL: not eligible for autologous HCT, not eligible for conventional myeloablative HCT, or after failed autologous HCT;
- Low grade NHL: with < 6 month duration of complete response (CR) between courses of conventional therapy;
- Mantle cell NHL: may be treated in first CR;
- Chronic lymphocytic leukemia (CLL): must have failed 2 lines of conventional therapy and must be refractory to fludarabine; this includes patients who fail to have a complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog] or experience disease relapse within 12 months after completing therapy with a regimen containing fludarabine [or another nucleoside analog);
- Hodgkin's disease (HD): must have received and failed frontline therapy and have failed or were not eligible for autologous transplant;
- Multiple myeloma (MM): must have received prior chemotherapy or failed autografting; following a planned autologous transplant [tandem] is allowed;
- Acute myeloid leukemia (AML): must have < 5% marrow blasts at the time of transplant;
- Acute lymphocytic leukemia (ALL): must have < 5% marrow blasts at the time of transplant;
- Chronic myelogenous leukemia (CML): patients will be accepted beyond first clinical progression (CP1) if they have received previous myelosuppressive chemotherapy or HCT, and have < 5% marrow blasts at time of transplant;
- Myelodysplastic syndrome/myeloproliferative disease (MDS/MPD): must have failed previous myelosuppressive chemotherapy or HCT, and have < 5% marrow blasts at time of transplant;
- Waldenstrom's macroglobulinemia: must have failed 2 courses of therapy
- Patient refuses to be treated on a conventional transplant protocol; for this inclusion criteria, transplants must be approved by both the participating institution's patient review committee, such as the Patient Care Conference (PCC) at the Fred Hutchinson Cancer Research Center (FHCRC), and the FHCRC principal investigator
Patient with related or unrelated donors for whom:
- There is a likelihood of disease progression while HLA typing and results of a preliminary search and the donor pool suggest that a 10/10 HLA-A, B, C, DRB1 and DQB1 matched unrelated donor will not be found;
- Patient and donor must be matched for at least one DRB1 allele and one DQB1 allele;
- Best available matches are HLA class I HLA-A, -B, -C allele matched donors allowing for any one or two DRB1 and/or DQB1 antigen/allele mismatch;
- There is no indication for an autologous transplantation as a treatment option
- DONOR: For HLA matching inclusion criteria, see patient inclusion criteria
- DONOR: Only peripheral blood stem cells (PBSC) will be permitted as a HSC source on this protocol
Exclusion Criteria:
- Positive crossmatch between donor and recipients
- Patient's life expectancy is severely limited by diseases other than malignancy
- Patient has central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy
- Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with AML, ALL or CML
- Patient is a fertile man or woman unwilling to use contraceptives during and for up to 12 months post treatment
- Patient is a female who is pregnant or breastfeeding
- Patient is human immunodeficiency virus (HIV) positive
- Patients with active non-hematologic malignancies (except non-melanoma skin cancers)
- Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence
- Patient has a fungal infection with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
Patient has the following organ dysfunction:
- Symptomatic coronary artery disease or ejection fraction < 35% or other cardiac failure requiring therapy; ejection fraction is required if age > 50 years or if the patient has a history of anthracyclines or history of cardiac disease;
- Diffusion capacity of the lung for carbon monoxide (DLCO) < 35% total lung capacity (TLC) < 35%, forced expiratory volume of the lung in one second (FEV1) < 35% and/or receiving supplementary continuous oxygen; the FHCRC study principal investigator (PI) must approve enrollment of all patients with pulmonary nodules;
- Liver function abnormalities: patient with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; the patient will be excluded if he/she is found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dL, or symptomatic biliary disease
- Patient has poorly controlled hypertension and on multiple antihypertensives
- Karnofsky performance score < 70 for adult patients
- Lansky play-performance score < 70 for pediatric patients
- Patient received cytotoxic agents for "cytoreduction" within three weeks (or the interval in which a cycle of standard chemotherapy would be administered in a non-transplant setting) prior to initiating the nonmyeloablative transplant conditioning; (exceptions are hydroxyurea and imatinib mesylate)
- DONOR: Marrow donors
- DONOR: Positive crossmatch between donor and recipient
- DONOR: Donor is HIV-positive and/or has a medical condition that would result in increased risk for filgrastim (G-CSF) mobilization and harvest of PBSC
- DONOR: Donor age < 12 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: Treatment (chemotherapy, TBI, transplant)
NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive alemtuzumab IV over 6 hours once daily on days -6, -5, and -4 OR days -5 and -4 and fludarabine phosphate IV over 30 minutes on days -4, -3, and -2. Patients also undergo low-dose TBI on day 0. ALLOGENEIC PBSCT: After completion of TBI, patients undergo allogeneic PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine PO or IV every 12 hours on days -3 to 180 followed by a taper until day 365 in the absence of GVHD. Beginning 4-6 hours after completion of allogeneic PBSCT, patients receive mycophenolate mofetil PO every 8 hours on days 0 to 100 followed by a taper until day 156 in the absence of GVHD. |
Korrelative Studien
Gegeben IV
Andere Namen:
Unterziehe dich einer PBSCT
Andere Namen:
PO gegeben
Andere Namen:
Gegeben IV
Andere Namen:
Unterziehen Sie sich einer niedrig dosierten TBI
Andere Namen:
Gegeben PO oder IV
Andere Namen:
Unterziehen Sie sich einer allogenen Stammzelltransplantation
Undergo GVHD prophylaxis/therapy
Andere Namen:
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Incidence of Grade III-IV Acute GVHD
Zeitfenster: 100 days after transplant
|
Severity of Individual Organ Involvement Liver: Stage 2 - bilirubin (3-5.9mg/100ml) Stage 3 - bilirubin (6-14.9mg/100ml) Stage 4 - bilirubin > 15mg/100ml Gut: Diarrhea is graded stage 1 to stage 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as stage 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall Severity of GVHD Grade III - Stage 2 to 4 gastrointestinal involvement and/or Stage 2 to 4 liver involvement with or without a rash Grade IV - Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death |
100 days after transplant
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Incidence of Graft Rejection
Zeitfenster: 84 days after transplant
|
Percentage patients that experienced graft rejection.
|
84 days after transplant
|
Incidence of High-dose Corticosteroid Utilization.
Zeitfenster: 100 days after transplant
|
Percentage patients requiring steroids greater than 1 mg/kg.
|
100 days after transplant
|
Incidence of Non-relapse Mortality
Zeitfenster: 100 days after transplant
|
Percentage patient deaths due to non-relapse mortality
|
100 days after transplant
|
Incidence of Infection
Zeitfenster: Up to 5 years post-transplant
|
Percentage patients that experienced infection(s).
|
Up to 5 years post-transplant
|
Immune Reconstitution
Zeitfenster: Up to 1 year post-transplant
|
The outcome of immune reconstitution was not analyzed by the collaborating laboratory because only a small number of patients were only enrolled in Dose Level 1 (no alemtuzumab).
The Dose Level 1 patients were going to be the baseline for which to compare the other patients on Dose Level 2 (and 3) who would have received alemtuzumab.
The collaborating investigator determined that the study was not worthwhile performing based on this information.
|
Up to 1 year post-transplant
|
Disease Progression/Relapse
Zeitfenster: Up to 5 years
|
CML New cytogenetic abnormality and/or development of accelerated phase or blast crisis. The criteria for accelerated phase will be defined as unexplained fever greater than 38.3°C, new clonal cytogenetic abnormalities in addition to a single Ph-positive chromosome, marrow blasts and promyelocytes >20%. AML, ALL >5% marrow blasts by morphologic or flow cytometric, or appearance of extramedullary disease. CLL ≥1 of: Physical exam/Imaging studies (nodes, liver, and/or spleen) ≥50% increase or new, circulating lymphocytes by morphology and/or flow cytometry ≥50% increase, and lymph node biopsy w/ Richter's transformation. NHL >25% increase in the sum of the products of the perpendicular diameters of marker lesions, or the appearance of new lesions. MM ≥100% increase of the serum myeloma protein from its lowest level, or reappearance of myeloma peaks that had disappeared w/ treatment; or definite increase in the size or number of plasmacytomas or lytic bone lesions. |
Up to 5 years
|
Mitarbeiter und Ermittler
Sponsor
Mitarbeiter
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn
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
- Pathologische Prozesse
- Herz-Kreislauf-Erkrankungen
- Gefäßerkrankungen
- Viruserkrankungen
- Infektionen
- Erkrankungen des Immunsystems
- Neubildungen, Binde- und Weichgewebe
- Neubildungen nach histologischem Typ
- Neubildungen
- Lymphoproliferative Erkrankungen
- Lymphatische Erkrankungen
- Immunproliferative Erkrankungen
- Neubildungen nach Standort
- Krankheitsattribute
- Erkrankung
- Erkrankungen des Knochenmarks
- Hämatologische Erkrankungen
- Hämorrhagische Störungen
- Hämostasestörungen
- Paraproteinämien
- Bluteiweißstörungen
- DNA-Virusinfektionen
- Bakterielle Infektionen und Mykosen
- Tumorvirusinfektionen
- Neubildungen, Plasmazelle
- Krebsvorstufen
- Epstein-Barr-Virus-Infektionen
- Herpesviridae-Infektionen
- Leukämie, B-Zell
- Neubildungen, Bindegewebe
- Neubildungen des Auges
- Lymphadenopathie
- Mastozytose, systemisch
- Mastozytose
- Lymphom
- Lymphom, follikulär
- Lymphom, B-Zell
- Lymphom, große B-Zelle, diffus
- Syndrom
- Myelodysplastische Syndrome
- Multiples Myelom
- Leukämie
- Leukämie, Myeloid
- Leukämie, myeloisch, akut
- Hodgkin-Krankheit
- Wiederauftreten
- Lymphom, Non-Hodgkin
- Präleukämie
- Leukämie, myelomonozytär, akut
- Leukämie, myelomonozytär, chronisch
- Leukämie, myelomonozytär, juvenil
- Mykosen
- Burkitt-Lymphom
- Lymphom, Mantelzelle
- Lymphom, B-Zelle, Randzone
- Vorläuferzelle lymphoblastische Leukämie-Lymphom
- Lymphom, großzellig, immunoblastisch
- Plasmablastisches Lymphom
- Waldenstrom-Makroglobulinämie
- Leukämie, lymphozytär, chronisch, B-Zell
- Leukämie, lymphatisch
- Lymphom, T-Zell
- Lymphom, T-Zelle, peripher
- Leukämie, myeloische, chronische, BCR-ABL-positiv
- Leukämie, myeloische, chronische Phase
- Lymphom, T-Zelle, Haut
- Leukämie, T-Zell
- Leukämie-Lymphom, erwachsene T-Zelle
- Mycosis fungoides
- Sezary-Syndrom
- Lymphom, großzellig, anaplastisch
- Lymphomatoide Granulomatose
- Lymphom, extranodale NK-T-Zelle
- Intraokulares Lymphom
- Immunoblastische Lymphadenopathie
- Myeloproliferative Erkrankungen
- Myelodysplastische-myeloproliferative Erkrankungen
- Leukämie, Haarzelle
- Leukämie, myeloisch, chronisch, atypisch, BCR-ABL-negativ
- Leukämie, Mastzelle
- Physiologische Wirkungen von Arzneimitteln
- Molekulare Mechanismen der pharmakologischen Wirkung
- Antiinfektiva
- Enzym-Inhibitoren
- Antirheumatika
- Antimetaboliten, antineoplastisch
- Antimetaboliten
- Antineoplastische Mittel
- Immunsuppressive Mittel
- Immunologische Faktoren
- Dermatologische Wirkstoffe
- Antibakterielle Mittel
- Antibiotika, antineoplastische
- Antimykotika
- Antituberkulöse Mittel
- Antibiotika, Antituberkulose
- Calcineurin-Inhibitoren
- Antikörper
- Immunglobuline
- Antikörper, monoklonal
- Antineoplastische Mittel, immunologische
- Fludarabin
- Fludarabinphosphat
- Mycophenolsäure
- Cyclosporin
- Cyclosporine
- Alemtuzumab
Andere Studien-ID-Nummern
- 1959.00 (Andere Kennung: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium)
- P30CA015704 (US NIH Stipendium/Vertrag)
- NCI-2009-01496 (Registrierungskennung: CTRP (Clinical Trial Reporting Program))
- P01CA018029 (US NIH Stipendium/Vertrag)
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .
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