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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Gruppo Italiano Malattie EMatologiche dell'Adulto
Sponsor:
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier:
NCT01762202
First received: January 4, 2013
Last updated: January 30, 2014
Last verified: January 2014
  Purpose

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).


Condition Intervention Phase
B-cell Lymphoid Leukemia
Young Patients
Drug: Cyclophosphamide
Drug: Fludarabine
Drug: Ofatumumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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).

Resource links provided by NLM:


Further study details as provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:

Primary Outcome Measures:
  • Number of complete responses. [ Time Frame: After 8 months from study entry. ] [ Designated as safety issue: No ]
    The complete response (CR) rate after FCO2 front-line treatment.


Secondary Outcome Measures:
  • Number of overall responses. [ Time Frame: After 8 months from study entry. ] [ Designated as safety issue: No ]
    Overall Response (OR) rate after FCO2 front-line treatment.

  • Number of patients in progression-free survival. [ Time Frame: After 32 months from study entry. ] [ Designated as safety issue: No ]
    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.

  • Number of patients needing a new CLL Treatment. [ Time Frame: After 32 months from study entry. ] [ Designated as safety issue: No ]
    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.

  • Number of patients in overall survival [ Time Frame: After 32 months from study entry. ] [ Designated as safety issue: No ]
    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.

  • Number of toxic events. [ Time Frame: After 32 months from study entry. ] [ Designated as safety issue: Yes ]
    Toxicity of treatment according the last NCI criteria.

  • Outcome of patients according to clinical and biologica variables. [ Time Frame: After 32 months from study entry. ] [ Designated as safety issue: No ]
    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).


Estimated Enrollment: 80
Study Start Date: November 2013
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Study therapy Drug: Cyclophosphamide Drug: Fludarabine Drug: Ofatumumab

Detailed Description:

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.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01762202

Contacts
Contact: Paola Fazi, Dr. p.fazi@gimema.it
Contact: Enrico Crea e.crea@gimema.it

Locations
Italy
S.O.C. di Ematologia - Azienda Ospedaliera - SS. Antonio e Biagio e Cesare Arrigo Recruiting
Alessandria, Italy
Contact: Silvia Baraldi         
Principal Investigator: Anna Baraldi         
Sub-Investigator: Flavia Salvi         
Dipartimento Area Medica - Presidio Ospedaliero "C. e G.Mazzoni" Not yet recruiting
Ascoli, Italy
Contact: Piero Galieni         
Principal Investigator: Piero Galieni         
Sub-Investigator: Emanuela Troiani         
UO Ematologia con trapianto-Università degli Studi di Bari Aldo Moro Not yet recruiting
Bari, Italy
Contact: Giorgina Specchia         
Principal Investigator: Giorgina Specchia         
Sub-Investigator: Anna Maria Giordano         
U.O.C. di Onco-Ematologia - Centro di Ricerca e Formazione ad Alta tecnologia nelle Scienze Biomediche Not yet recruiting
Campobasso, Italy
Contact: Sergio Storti         
Principal Investigator: Sergio Storti         
Sub-Investigator: Vincenzo Fraticelli         
Azienda Ospedaliera Pugliese Ciaccio - Presidio Ospedaliero A.Pugliese - Unità Operativa di Ematologia Recruiting
Catanzaro, Italy
Contact: Stefano Molica         
Principal Investigator: Stefano Molica         
Sub-Investigator: Rosanna Mirabelli         
Sezione di Ematologia e Fisiopatologia delle Emostasi - Azienda Ospedaliera - Arcispedale S. Anna Not yet recruiting
Ferrara, Italy
Contact: Antonio Cuneo         
Principal Investigator: Antonio Cuneo         
Sub-Investigator: Gian Matteo Rigolin         
Policlinico Careggi Not yet recruiting
Firenze, Italy
Contact: Alberto Bosi, Dr.         
Principal Investigator: Alberto Bosi, Dr.         
Sub-Investigator: Stefania Ciolli, Dr.         
RCCS_AOU San Martino-IST-Ematologia 1-Monoblocco 11°piano- lato ponente Recruiting
Genova, Italy
Contact: Angelo Michele Carella         
Principal Investigator: Angelo Michele Carella         
Sub-Investigator: Mauro Spriano         
ASL Le/1 P.O. Vito Fazzi - U.O. di Ematologia ed UTIE Not yet recruiting
Lecce, Italy
Contact: Nicola Di Renzo         
Principal Investigator: Nicola Di Renzo         
Sub-Investigator: M.R. De Paolis         
Divisione di Ematologia - Azienda Ospedaliera Ospedali Riuniti "Papardo Piemonte" Not yet recruiting
Messina, Italy
Contact: Maura Brugiatelli, Dr.         
Principal Investigator: Maura Brugiatelli, Pr.         
Sub-Investigator: Laura Nocilli, Dr.         
Azienda Ospedaliera Universitaria - Policlinico G. Martino Dipartimento di Medicina Interna - U.O. Messina Not yet recruiting
Messina, Italy
Contact: Caterina Musolino         
Principal Investigator: Caterina Musolino         
Sub-Investigator: Alessandro Allegra         
Ospedale Niguarda " Ca Granda" Not yet recruiting
Milano, Italy
Contact: Alessandria Tedeschi, Dr.         
Principal Investigator: Alessandria Tedeschi, Dr.         
Sub-Investigator: Marco Montillo, Dr.         
UO Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico Not yet recruiting
Milano, Italy
Contact: Agostino Cortelezzi, Dr.         
Principal Investigator: Agostino Cortelezzi, Dr.         
Sub-Investigator: Gianluca Reda, Dr.         
S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro Not yet recruiting
Novara, Italy
Contact: Gianluca Gaidano         
Principal Investigator: Gianluca Gaidano         
Sub-Investigator: Davide Rossi         
Divisione di Ematologia con trapianto di midollo - A.U. Policlinico "Paolo Giaccone" Not yet recruiting
Palermo, Italy
Contact: Sergio Siragusa         
Principal Investigator: Sergio Siragusa         
Sub-Investigator: Simona Raso         
Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli" Not yet recruiting
Reggio Calabria, Italy
Contact: Francesco Nobile, Dr.         
Principal Investigator: Francesco Nobile, Dr.         
Sub-Investigator: Donatella Vincelli, Dr.         
Ospedale "Infermi" Not yet recruiting
Rimini, Italy
Contact: Anna Lia, Dr.         
Principal Investigator: Anna Lia, Dr.         
Sub-Investigator: Anna Merli, Dr.         
U.O.C. Ematologia - Ospedale S.Eugenio Not yet recruiting
Roma, Italy
Contact: Giovanni Del Poeta         
Principal Investigator: Giovanni Del Poeta         
Sub-Investigator: Dario Raguso         
Policlinico Umberto I, Hematology Department - Sapienza Not yet recruiting
Roma, Italy
Contact: Roberto Foà         
Principal Investigator: Roberto Foà, Pr.         
Sub-Investigator: Francesca R. Mauro, Dr.         
Università Cattolica del Sacro Cuore - Policlinico A. Gemelli Not yet recruiting
Roma, Italy
Contact: Luca Laurenti, Dr.         
Principal Investigator: Luca Laurenti, Dr.         
Sub-Investigator: Barbara Vannata, Dr.         
Università degli Studi - Policlinico di Tor Vergata Not yet recruiting
Roma, Italy
Contact: Sergio Amadori         
Principal Investigator: Sergio Amadori         
Sub-Investigator: Ilaria Del Principe         
U.O.C. Ematologia e Trapianti - A.O. Senese - Policlinico " Le Scotte" Not yet recruiting
Siena, Italy
Contact: Monica Bocchia         
Principal Investigator: Monica Bocchia         
SS.C. di Oncoematologia - Dipartimento di Medicina Clinica e Sperimentale - Azienda Ospedaliera - S. Maria Di Terni Recruiting
Terni, Italy
Contact: Anna Marina Liberati         
Principal Investigator: Anna Marina Liberati         
Sub-Investigator: Ilaria Angeletti         
Div. di Ematologia Ospedale "S.Giovanni Battista" Not yet recruiting
Torino, Italy
Contact: Massimo Massaia         
Principal Investigator: Massimo Massaia         
Sub-Investigator: Marta Coscia         
SCDO Ematologia 2 AOU S.Giovanni Battista Not yet recruiting
Torino, Italy
Contact: Lorella Orsucci         
Principal Investigator: Lorella Orsucci         
Sub-Investigator: Patrizia Pregno         
Clinica Ematologica - Policlinico Universitario Recruiting
Udine, Italy
Contact: Francesco Zaja         
Principal Investigator: Francesco Zaja         
Principal Investigator: Maddalena Mazzucco         
Università degli Studi di Verona - A. O. - Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi Not yet recruiting
Verona, Italy
Contact: Achille Ambrosetti         
Principal Investigator: Achille Ambrosetti         
Sub-Investigator: Roberta Zanotti         
Sponsors and Collaborators
Gruppo Italiano Malattie EMatologiche dell'Adulto
Investigators
Study Chair: Roberto Foà, Pr. Policlinico Umberto I, Hematology Department.
Study Director: Francesca R. Mauro Policlinico Umberto I, Hematology Department.
  More Information

No publications provided

Responsible Party: Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier: NCT01762202     History of Changes
Other Study ID Numbers: CLL0911, 2011-005329-27
Study First Received: January 4, 2013
Last Updated: January 30, 2014
Health Authority: Italy: Ethics Committee

Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:
CLL
Fludarabine
Cyclophosphamide
Ofatumumab

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on September 18, 2014