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Assessment of Efficacy and Safety of Front-line Fludarabine, Cyclophoshamide and Ofatumumab Chemoimmunotherapy in Young Patients With Chronic Lymphocytic Leukemia. (CLL0911)

12 oktober 2020 uppdaterad av: Gruppo Italiano Malattie EMatologiche dell'Adulto

Phase 2 Multicenter, Study to Assess the Efficacy and the Safety of Front-line Fludarabine, Cyclophoshamide and Ofatumumab (FCO2) Chemoimmunotherapy in Young (≤65 Yrs) Patients With Chronic Lymphocytic Leukemia (CLL).

Assessment of safety and efficacy of with fludarabine and cyclophosphamide (FC) combined with ofatumumab (FCO2) in previously untreated "young" patients with Chronic Lymphocytic Leukemia (CLL).

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Detaljerad beskrivning

Given that:

  • rituximab, fludarabine and cyclophosphamide (FCR) front-line treatment was associated with a high OR rate, superior PFS and OS as compared to fludarabine and cyclophosphamide regimen;
  • a direct relationship between the dose of rituximab and the response rate has been reported;
  • ofatumumab, as single agent, proved activity in CLL patients with refractory disease;
  • ofatumumab, fludarabine and cylophosphamide (O-FC) front-line treatment has been associated with a high complete response (CR) rate;
  • the expected grade 3-4 granulocytopenia could led to reduce the dose intensity of study drugs (FC) and increase the infection rate; a schedule combining FC with an increased dose of ofatumumab associated to primary phrophylaxis of granulocytopenia could be associated with an improvement in the CR rate. The purpose of this study is to determine whether we could improve the CR rate of the golden standard treatment for fit patients with CLL , the FCR regimen, with a chemoimmunotherapy including FC combined with an increased dose of the monoclonal antibody ofatumumab, given every other week (FCO2) associated with a primary prophylaxis of granulocytopenia.

Studietyp

Interventionell

Inskrivning (Faktisk)

80

Fas

  • Fas 2

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Italien
      • Alessandria, Italien
        • S.O.C. di Ematologia - Azienda Ospedaliera - SS. Antonio e Biagio e Cesare Arrigo
      • Ascoli Piceno, Italien
        • Dipartimento Area Medica - Presidio Ospedaliero "C. e G.Mazzoni"
      • Asti, Italien
        • S.O.C. di Medicina Interna B - Ospedale - Cardinal Massaia di Asti
      • Biella, Italien
        • ASL12 - Biella Ospedale degli Infermi - Dip. di Medicina e Geriatria - Struttura Complessa di Medicina Interna
      • Catanzaro, Italien
        • Azienda Ospedaliera Pugliese Ciaccio - Presidio Ospedaliero A.Pugliese - Unità Operativa di Ematologia
      • Ferrara, Italien
        • Sezione di Ematologia e Fisiopatologia delle Emostasi - Azienda Ospedaliera - Arcispedale S. Anna
      • Genova, Italien
        • RCCS_AOU San Martino-IST-Ematologia 1-Monoblocco 11°piano- lato ponente
      • Lecce, Italien
        • ASL Le/1 P.O. Vito Fazzi - U.O. di Ematologia ed UTIE
      • Messina, Italien
        • Azienda Ospedaliera Universitaria - Policlinico G. Martino Dipartimento di Medicina Interna - U.O. Messina
      • Milano, Italien
        • Ospedale Niguarda " Ca Granda"
      • Novara, Italien
        • S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro
      • Palermo, Italien
        • Divisione di Ematologia con trapianto di midollo - A.U. Policlinico "Paolo Giaccone"
      • Parma, Italien
        • Cattedra di Ematologia CTMO Università degli Studi di Parma
      • Reggio Calabria, Italien
        • Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"
      • Reggio Emilia, Italien
        • Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova
      • Roma, Italien
        • U.O.C. Ematologia - Ospedale S.Eugenio
      • Roma, Italien
        • Padiglione Cesalpino - I piano - Divisione di Ematologia - Ospedale S. Camillo
      • Roma, Italien
        • Policlinico Umberto I, Hematology Department - Sapienza
      • Siena, Italien
        • U.O.C. Ematologia e Trapianti - A.O. Senese - Policlinico " Le Scotte"
      • Terni, Italien
        • SS.C. di Oncoematologia - Dipartimento di Medicina Clinica e Sperimentale - Azienda Ospedaliera - S. Maria Di Terni
      • Torino, Italien
        • Div. di Ematologia Ospedale "S.Giovanni Battista"
      • Udine, Italien
        • Clinica Ematologica - Policlinico Universitario

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år till 65 år (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

Inclusion Criteria:

  • B-cell CLL diagnosis by 2008 revised IWCLL criteria.
  • Treatment requirement according to the 2008 revised IWCLL criteria.
  • No previous treatment.
  • Age > 18 year and . 65 years.
  • ECOG performance status of 0-1 at study entry and CIRS score .6.
  • Adequate renal function (creatinine clearance.60 ml/min estimated using the Cockcroft-Gaultequation) .
  • For male and female subjects of childbearing potential, agreement to use effective contraception.
  • Signed written informed const according to ICH/EU/GCP and national local laws.

Exclusion Criteria:

  • Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease and/or laboratory abnormality which in the opinion of the investigator may represent a risk for the patient and/or that would prevent the subject from signing the informed consent form.
  • Pregnant or lactating females.
  • Known positive serology for HIV.
  • Positive serology for Hepatitis B (HBV) defined as a positive test for HBsAg and HBV-DNA.
  • HCV-RNA positive.
  • Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection, tuberculosis and active hepatitis.
  • History of tuberculosis within the last five years or recent exposure to tuberculosis equal to or less than 6 months.
  • Known presence of alcohol and/or drug abuse.
  • Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to the inclusion in the study, congestive heart failure (NYHA III-IV), arrhythmia unless controlled by therapy.. grade 2 neuropathy; history of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae.
  • Uncontrolled autoimmune hemolytic anemia or thrombocytopenia.

  • One or more laboratory abnormalities:

    1. Calculated creatinine clearance (Cockroft-Gault)<60mL/min.
    2. Absolute granulocyte count <1500/ƒÊL not disease related.
    3. Platelet count < 75000/ƒÊL not disease related.
    4. GOT, GPT, GT, alkaline phosphatase > 1,5 x upper limit of normal value unless due to disease involvement); serum bilirubin >1.5mg/dL, subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones)
  • Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study
  • Other past or current malignancy. Subjects who have been free of malignancy for at least 5 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: N/A
  • Interventionsmodell: Enskild gruppuppgift
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Study therapy
Läkemedel: Cyklofosfamid
Läkemedel: Fludarabin
Läkemedel: Ofatumumab

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Number of complete responses.
Tidsram: After 8 months from study entry.
The complete response (CR) rate after FCO2 front-line treatment.
After 8 months from study entry.

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Number of overall responses.
Tidsram: After 8 months from study entry.
Overall Response (OR) rate after FCO2 front-line treatment.
After 8 months from study entry.
Number of patients in progression-free survival.
Tidsram: After 32 months from study entry.
Progression-free survival (PFS) calculated from the date of first treatment dose - induction phase - until the date of the first documentation of progressive disease or until death (whatever the cause), whichever occurs first. Patients still alive and known to be progression free will be censored at the moment of last follow-up.
After 32 months from study entry.
Number of patients needing a new CLL Treatment.
Tidsram: After 32 months from study entry.
Time to a new CLL treatment (TTT) will be calculated from the date of last treatment dose until date of a new treatment received for CLL, where death occurred before the new treatment will be considered as competing risk. Patients still alive without receiving a new treatment will be censored at the time of the last follow-up.
After 32 months from study entry.
Number of patients in overall survival
Tidsram: After 32 months from study entry.
Overall survival (OS): defined as the time interval between the date of first treatment dose - induction phase- and the date of death for any cause; patients still alive will be censored at the moment of last follow-up.
After 32 months from study entry.
Number of toxic events.
Tidsram: After 32 months from study entry.
Toxicity of treatment according the last NCI criteria.
After 32 months from study entry.
Outcome of patients according to clinical and biologica variables.
Tidsram: After 32 months from study entry.
Outcome of patients (response, PFS OS) according to clinical and biologic variables (age; size of nodes, 2-microglobulin, lymphocyte count, stage, IgVH, p53, FISH, ZAP-70, CD38, FLCs).
After 32 months from study entry.

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Gruppo Italiano Malattie EMatologiche dell'Adulto

Utredare

  • Studiestol: Roberto Foà, Pr., Policlinico Umberto I, Hematology Department.
  • Studierektor: Francesca R. Mauro, Policlinico Umberto I, Hematology Department.

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Användbara länkar

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

5 november 2013

Primärt slutförande (Faktisk)

1 november 2015

Avslutad studie (Faktisk)

1 oktober 2018

Studieregistreringsdatum

Först inskickad

4 januari 2013

Först inskickad som uppfyllde QC-kriterierna

4 januari 2013

Första postat (Uppskatta)

7 januari 2013

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

14 oktober 2020

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

12 oktober 2020

Senast verifierad

1 oktober 2020

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • CLL0911
  • 2011-005329-27 (EudraCT-nummer)

Plan för individuella deltagardata (IPD)

Planerar du att dela individuella deltagardata (IPD)?

NEJ

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