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

Sponsor

Gruppo Italiano Malattie EMatologiche dell'Adulto (Other)

Overall Status

Completed

CT.gov ID

NCT01762202

Collaborator

(none)

Enrollment

Locations

Arm

58.8

Actual Duration (Months)

3.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:

Interventional

Actual Enrollment :

80 participants

Allocation:

N/A

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).

Actual Study Start Date :

Nov 5, 2013

Actual Primary Completion Date :

Nov 1, 2015

Actual Study Completion Date :

Oct 1, 2018

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Study therapy

Drug: Cyclophosphamide

Drug: Fludarabine

Drug: Ofatumumab

Outcome Measures

Primary Outcome Measures

Number of complete responses. [After 8 months from study entry.]
The complete response (CR) rate after FCO2 front-line treatment.

Secondary Outcome Measures

Number of overall responses. [After 8 months from study entry.]
Overall Response (OR) rate after FCO2 front-line treatment.
Number of patients in progression-free survival. [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.
Number of patients needing a new CLL Treatment. [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.
Number of patients in overall survival [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.
Number of toxic events. [After 32 months from study entry.]
Toxicity of treatment according the last NCI criteria.
Outcome of patients according to clinical and biologica variables. [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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Calculated creatinine clearance (Cockroft-Gault)<60mL/min.
Absolute granulocyte count <1500/ƒÊL not disease related.
Platelet count < 75000/ƒÊL not disease related.
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

Locations

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

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.