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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01762202
Recruitment Status : Active, not recruiting
First Posted : January 7, 2013
Last Update Posted : March 22, 2018
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto

Brief Summary:
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 or disease Intervention/treatment Phase
B-cell Lymphoid Leukemia Young Patients Drug: Cyclophosphamide Drug: Fludarabine Drug: Ofatumumab Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Intervention Model: Single Group Assignment
Masking: None (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).
Study Start Date : November 2013
Actual Primary Completion Date : November 2015
Estimated Study Completion Date : May 2018

Arm Intervention/treatment
Experimental: Study therapy Drug: Cyclophosphamide
Drug: Fludarabine
Drug: Ofatumumab

Primary Outcome Measures :
  1. Number of complete responses. [ Time Frame: After 8 months from study entry. ]
    The complete response (CR) rate after FCO2 front-line treatment.

Secondary Outcome Measures :
  1. Number of overall responses. [ Time Frame: After 8 months from study entry. ]
    Overall Response (OR) rate after FCO2 front-line treatment.

  2. Number of patients in progression-free survival. [ Time Frame: 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.

  3. Number of patients needing a new CLL Treatment. [ Time Frame: 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.

  4. Number of patients in overall survival [ Time Frame: 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.

  5. Number of toxic events. [ Time Frame: After 32 months from study entry. ]
    Toxicity of treatment according the last NCI criteria.

  6. Outcome of patients according to clinical and biologica variables. [ Time Frame: 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).

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01762202

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

Additional Information:
Responsible Party: Gruppo Italiano Malattie EMatologiche dell'Adulto Identifier: NCT01762202     History of Changes
Other Study ID Numbers: CLL0911
2011-005329-27 ( EudraCT Number )
First Posted: January 7, 2013    Key Record Dates
Last Update Posted: March 22, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:

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