Clinical trial NCT01762202: Assessment of Efficacy and Safety of Front-line Fludarabine, Cyclophoshamide and Ofatumumab Chemoimmunotherapy in Young Patients With Chronic Lymphocytic Leukemia.
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: B-cell Lymphoid Leukemia
Young Patients
Keywords: CLL
Fludarabine
Cyclophosphamide
Ofatumumab
Lead sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
Sponsor class: OTHER
First posted: 2013-01-07
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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 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.

Primary outcomes:
measure: Number of complete responses.
timeFrame: After 8 months from study entry.
Secondary outcomes:
measure: Number of overall responses.
timeFrame: After 8 months from study entry.
measure: Number of patients in progression-free survival.
timeFrame: After 32 months from study entry.
measure: Number of patients needing a new CLL Treatment.
timeFrame: After 32 months from study entry.
measure: Number of patients in overall survival
timeFrame: After 32 months from study entry.
measure: Number of toxic events.
timeFrame: After 32 months from study entry.
measure: Outcome of patients according to clinical and biologica variables.
timeFrame: After 32 months from study entry.
Other outcomes:
Locations:
city: Alessandria
country: Italy
facility: S.O.C. di Ematologia - Azienda Ospedaliera - SS. Antonio e Biagio e Cesare Arrigo
city: Ascoli Piceno
country: Italy
facility: Dipartimento Area Medica - Presidio Ospedaliero "C. e G.Mazzoni"
city: Asti
country: Italy
facility: S.O.C. di Medicina Interna B - Ospedale - Cardinal Massaia di Asti
city: Biella
country: Italy
facility: ASL12 - Biella Ospedale degli Infermi - Dip. di Medicina e Geriatria - Struttura Complessa di Medicina Interna
city: Catanzaro
country: Italy
facility: Azienda Ospedaliera Pugliese Ciaccio - Presidio Ospedaliero A.Pugliese - Unità Operativa di Ematologia
city: Ferrara
country: Italy
facility: Sezione di Ematologia e Fisiopatologia delle Emostasi - Azienda Ospedaliera - Arcispedale S. Anna
city: Genova
country: Italy
facility: RCCS_AOU San Martino-IST-Ematologia 1-Monoblocco 11°piano- lato ponente
city: Lecce
country: Italy
facility: ASL Le/1 P.O. Vito Fazzi - U.O. di Ematologia ed UTIE
city: Messina
country: Italy
facility: Azienda Ospedaliera Universitaria - Policlinico G. Martino Dipartimento di Medicina Interna - U.O. Messina
city: Milano
country: Italy
facility: Ospedale Niguarda " Ca Granda"
city: Novara
country: Italy
facility: S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro
city: Palermo
country: Italy
facility: Divisione di Ematologia con trapianto di midollo - A.U. Policlinico "Paolo Giaccone"
city: Parma
country: Italy
facility: Cattedra di Ematologia CTMO Università degli Studi di Parma
city: Reggio Calabria
country: Italy
facility: Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"
city: Reggio Emilia
country: Italy
facility: Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova
city: Roma
country: Italy
facility: Padiglione Cesalpino - I piano - Divisione di Ematologia - Ospedale S. Camillo
city: Roma
country: Italy
facility: Policlinico Umberto I, Hematology Department - Sapienza
city: Roma
country: Italy
facility: U.O.C. Ematologia - Ospedale S.Eugenio
city: Siena
country: Italy
facility: U.O.C. Ematologia e Trapianti - A.O. Senese - Policlinico " Le Scotte"
city: Terni
country: Italy
facility: SS.C. di Oncoematologia - Dipartimento di Medicina Clinica e Sperimentale - Azienda Ospedaliera - S. Maria Di Terni
city: Torino
country: Italy
facility: Div. di Ematologia Ospedale "S.Giovanni Battista"
city: Udine
country: Italy
facility: Clinica Ematologica - Policlinico Universitario
Study officials:
affiliation: Policlinico Umberto I, Hematology Department.
name: Roberto Foà, Pr.
role: STUDY_CHAIR
affiliation: Policlinico Umberto I, Hematology Department.
name: Francesca R. Mauro
role: STUDY_DIRECTOR
References: