- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT02315118
Pilot Study of Autologous T Lymphocytes With ADCC in Patients With CD20-Positive B-Cell Malignancies
Pilot Study of Autologous T Lymphocytes With Antibody-Dependent Cell Cytotoxicity in Patients With CD20-Positive B-Cell Malignancies
Despite advancement in chemotherapy, radiotherapy and haematopoietic stem cell transplant (HSCT), and the recent introduction of more targeted therapies, a substantial proportion of patients with B-cell malignancies, such as B-cell chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin's lymphoma (NHL) still succumb to their malignancies. For CLL and low-grade NHL, cure is achievable only with HSCT but such aggressive approach is not justified as the initial therapy for most patients who have indolent disease; when disease has progressed, transplant is either not feasible or ineffective. For high-grade B-cell NHL, the availability of Rituximab has improved disease outcome but treatment failure portends nearly inevitable death from disease or treatment-related complications. Thus, newer, more effective therapies for patients with B-cell malignancies are urgently needed.
The present study translates recent laboratory findings into clinical application. In patients with B-cell malignancies receiving the anti-CD20 antibody Rituximab as standard therapy, the study aims to assess the feasibility and safety, as well as explore the efficacy, of infusing autologous T-lymphocytes engineered to express a CD16-41BB-CD3zeta chimeric receptor which mediates antibody-dependent cell cytotoxicity. Receptor expression is achieved by electroporation of mRNA.
Studienübersicht
Status
Intervention / Behandlung
Studientyp
Einschreibung (Voraussichtlich)
Phase
- Phase 2
- Phase 1
Kontakte und Standorte
Studienkontakt
- Name: Michelle Poon, MBBS, MRCP
- Telefonnummer: (65) 6779 5555
Studienorte
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Singapore, Singapur, 119228
- Rekrutierung
- National University Hospital
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Kontakt:
- Michelle Poon, MBBS, MRCP
- Telefonnummer: (65) 6779 5555
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Hauptermittler:
- Michelle Poon, MBBS, MRCP
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Hauptermittler:
- Yeh Ching Linn, MBBS, MRCP
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
Inclusion Criteria:
- Age: 6 months to 80 years old.
i) Diagnosis of aggressive CD20+ B-NHL with measurable tumor burden (by imaging, flow cytometry and/or PCR) post-treatment. This includes patients with persistent disease following more than 2 lines of chemotherapy, as well as patients who relapse following autologous transplantation, and in whom further salvage therapy has produced only a partial remission or where no effective salvage therapy available. Patients with bulky disease who require immediate salvage therapy will not be eligible.
OR ii) Diagnosis of poor risk indolent CD20+ B-NHL or Chronic Lymphocytic Leukemia. This includes high risk CLL cases with early relapse (<12 months following purine analog containing treatment or <24 months following autologous transplant), or with 17p deletion needing treatment, and who are not candidates (or refuses) allogeneic transplantation. Patients with advanced progressive indolent B-NHL with relapsed, refractory disease who have failed more than 2 lines of treatment (including autologous transplantation) may also be considered.
- Shortening fraction greater than or equal to 25%.
- Glomerular filtration rate greater than or equal to 50 ml/min/1.73 m2.
- Pulse oximetry greater than or equal to 92% on room air.
- Direct bilirubin less than or equal to 3.0 mg/dL (50 mmol/L).
- Alanine aminotransferase (ALT) is no more than 2 times the upper limit of normal unless determined to be directly due to disease.
- Aspartate transaminases (AST) is no more than 2 times the upper limit of normal unless determined to be directly due to disease.
- Karnofsky or Lansky performance score of greater than or equal to 50.
- No clinical history of or overt autoimmune disease.
- No past history of previous severe adverse reactions to rituximab, eg. cytokine release syndrome
- Has recovered from all acute NCI Common Toxicity Criteria grade II-IV non-hematologic acute toxicities resulting from prior therapy per the judgment of the PI.
- Is not receiving more than the equivalent of prednisone 10 mg daily.
- Not pregnant (negative serum or urine pregnancy test to be conducted within 7 days prior to enrollment).
- Not lactating.
Exclusion Criteria:
Failure to meet any of the inclusion criteria
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: T-cell therapy + Rituximab + IL-2
Patients will undergo apheresis procedure and T cell expansion will be done in the laboratory. All patients will receive Rituximab on day -2 and IL-2 three times per week for one week starting on day -1 (dose 1 of 3). IL-2 dosing will be continued 3 times per week for one week (3 doses total). On Day 0, T cell modification in the laboratory and T cell infusion in the patient will be done. A disease status evaluation will be conducted approximately 4 weeks post-T cell infusion. |
Andere Namen:
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Performance status assessed by age-dependent Performance Scores
Zeitfenster: One-month (30 days) after the last T cell infusion
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Using KARNOFSKY PERFORMANCE STATUS SCALE (Recipient Age ≥ 16 years) and LANSKY PERFORMANCE STATUS SCALE (Recipient Age < 16 years)
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One-month (30 days) after the last T cell infusion
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Toxicity criteria
Zeitfenster: One-month (30 days) after the last T cell infusion
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Participants will be monitored for toxicity for a period of one-month (30 days) after the last T cell infusion. Monitored toxicities will include the following:
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One-month (30 days) after the last T cell infusion
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Disease response criteria
Zeitfenster: One-month (30 days) after the last T cell infusion and at intervals thereafter till progression (approximately every 3 months for about a year)
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Response criteria follow those defined by NCCN Guidelines version 4.2011 for CLL and NHL. For monitoring of treatment response, patients with CLL and NHL will have PET-CT scan at approximately 1 month before and after infusion and at intervals thereafter till progression. Peripheral blood and bone marrow studies (the latter only if bone marrow is involved pre-treatment) will be done to determine levels of residual disease by using established flow cytometric and molecular MRD assays. |
One-month (30 days) after the last T cell infusion and at intervals thereafter till progression (approximately every 3 months for about a year)
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Persistence of CD16+ T cells and impact on B cell function
Zeitfenster: Up to approximately month
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Up to approximately month
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Mitarbeiter und Ermittler
Mitarbeiter
Ermittler
- Hauptermittler: Michelle Poon, MBBS, MRCP, National University Hospital, Singapore
Publikationen und hilfreiche Links
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn
Primärer Abschluss (Voraussichtlich)
Studienabschluss (Voraussichtlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Schätzen)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
- Erkrankungen des Immunsystems
- Neubildungen nach histologischem Typ
- Neubildungen
- Lymphoproliferative Erkrankungen
- Lymphatische Erkrankungen
- Immunproliferative Erkrankungen
- Leukämie, lymphatisch
- Leukämie
- Leukämie, B-Zell
- Leukämie, lymphozytär, chronisch, B-Zell
- Physiologische Wirkungen von Arzneimitteln
- Antirheumatika
- Antineoplastische Mittel
- Immunologische Faktoren
- Antineoplastische Mittel, immunologische
- Rituximab
Andere Studien-ID-Nummern
- 2014/00584
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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