Prospective Collection of Biological Data of Prognostic Relevance in Patients With B-Cell Chronic Lymphocytic Leukemia

Prospective Collection of Biological Data of Prognostic Relevance in Patients

The purpose of the present study is to develop a biological prognostic index in patients with Binet stage A Chronic Lymphocytic Leukemia (CLL) who do not necessitate therapy according to NCI guidelines and to prospectively validate the proposed score system based on the absence/presence of 1, 2 or 3 unfavorable prognostic markers such as cluster of differentiation 38 (CD38) expression, Zap-70 expression and immunoglobulin heavy chain variable region (IgVH) configuration.

Study Overview

• Status: Unknown
• Conditions: Chronic Lymphocytic Leukemia Stage A(0); Chronic Lymphocytic Leukemia Stage A(I); Chronic Lymphocytic Leukemia Stage A(II)

Detailed Description

Clinical data including information on disease localization and laboratory parameters will be collected at study entry, during follow up and at disease progression (or after 36 months after registration) Biological markers will be evaluated at centralized laboratory, at study entry and at time of disease progression (or after 24 months of follow-up for non progressed patients) Using the scoring system, patients can be separated into 3 risk groups: low-risk (score 0), intermediate-risk (score 1) and high-risk (score 2-3), with significantly different clinical courses.

• Study Type: Observational
• Enrollment (Anticipated): 495

Contacts and Locations

• Study Contact: Name: Fortunato Morabito, MD; Phone Number: +39 0984 681329; Email: fortunato_morabito@tin.it

Study Locations

• Italy
  • Modena, Italy, 41100
    • Recruiting
    • GISL Trial Office
    • Contact: Emanuela A Pesce, BSc; Phone Number: +39 059 422 2688; Email: emanuelaanna.pesce@unimore.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Previously untreated Binet stage A B-CLL patients, who do not necessitate therapy according to NCI guidelines

Description

Inclusion Criteria:

• Established diagnosis of B-CLL by NCI criteria, performed by local haematologist. (Diagnosis will be confirmed by the biological review committee according to flow cytometry analysis (positive clusters of differentiation antigen 5 (CD5), 19 (CD19),23 (CD23)).
• Age > 18 years and < 70 years.
• Eastern Cooperative Oncology Group (ECOG)<=2.
• Binet stage A.
• Diagnosis performed within 12 months before inclusion in the study.
• Patients who do not necessitate therapy by NCI guidelines (watch and wait policy).
• Shipment of peripheral blood sample to centralized laboratory for biological assessment.
• Clinical data including baseline information on disease localization and laboratory parameters at staging and assurance of follow up updating for at least 3 years are requested.
• Written informed consent.

Exclusion Criteria:

• Patients with CLL whose diagnosis exceed 12 months before registration.
• Patients with leukemic phase of lymphoproliferative disorders of B origin CD5- and/or CD23- according to flow cytometry analysis.
• Clinical Binet stage B or C.
• Patients who necessitate therapy according to NCI guide-lines (no watch and wait policy).
• Age > 70 years.
• Without a written informed consent.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Prospective validation of the prognostic potential of a score system based on the presence/absence of three risk factors (VH mutational status, Zap-70 and CD38 expression) on Progression Free Survival (PFS ).	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Quality of Life	6 months
Overall Survival	3 years
Time to Treatment	6 months

Collaborators and Investigators

• Sponsor: Gruppo Italiano Studio Linfomi
• Investigators: Study Chair: Fortunato Morabito, MD, GISL; Study Chair: Manlio Ferrarini, MD, GISL

Publications and helpful links

General Publications

• Kreuzberger N, Damen JA, Trivella M, Estcourt LJ, Aldin A, Umlauff L, Vazquez-Montes MD, Wolff R, Moons KG, Monsef I, Foroutan F, Kreuzer KA, Skoetz N. Prognostic models for newly-diagnosed chronic lymphocytic leukaemia in adults: a systematic review and meta-analysis. Cochrane Database Syst Rev. 2020 Jul 31;7(7):CD012022. doi: 10.1002/14651858.CD012022.pub2.
• Matis S, Grazia Recchia A, Colombo M, Cardillo M, Fabbi M, Todoerti K, Bossio S, Fabris S, Cancila V, Massara R, Reverberi D, Emionite L, Cilli M, Cerruti G, Salvi S, Bet P, Pigozzi S, Fiocca R, Ibatici A, Angelucci E, Gentile M, Monti P, Menichini P, Fronza G, Torricelli F, Ciarrocchi A, Neri A, Fais F, Tripodo C, Morabito F, Ferrarini M, Cutrona G. MiR-146b-5p regulates IL-23 receptor complex expression in chronic lymphocytic leukemia cells. Blood Adv. 2022 Oct 25;6(20):5593-5612. doi: 10.1182/bloodadvances.2021005726.
• Morabito F, Tripepi G, Vigna E, Bossio S, D'Arrigo G, Martino EA, Storino F, Recchia AG, Fronza G, Di Raimondo F, Colombo M, Fais F, Neri A, Cutrona G, Ferrarini M, Gentile M. Validation of the Alternative International Prognostic Score-E (AIPS-E): Analysis of Binet stage A chronic lymphocytic leukemia patients enrolled into the O-CLL1-GISL protocol. Eur J Haematol. 2021 Jun;106(6):831-835. doi: 10.1111/ejh.13614. Epub 2021 Apr 7.
• Morabito F, Cutrona G, Mosca L, D'Anca M, Matis S, Gentile M, Vigna E, Colombo M, Recchia AG, Bossio S, De Stefano L, Maura F, Manzoni M, Ilariucci F, Consoli U, Vincelli I, Musolino C, Cortelezzi A, Molica S, Ferrarini M, Neri A. Surrogate molecular markers for IGHV mutational status in chronic lymphocytic leukemia for predicting time to first treatment. Leuk Res. 2015 Aug;39(8):840-5. doi: 10.1016/j.leukres.2015.05.005. Epub 2015 May 19.
• Maura F, Mosca L, Fabris S, Cutrona G, Matis S, Lionetti M, Agnelli L, Barbieri M, D'Anca M, Manzoni M, Colombo M, Massucco C, Reverberi D, Gentile M, Recchia AG, Bossio S, Ilariucci F, Musolino C, Di Raimondo F, Cortelezzi A, Morabito F, Ferrarini M, Neri A. Insulin growth factor 1 receptor expression is associated with NOTCH1 mutation, trisomy 12 and aggressive clinical course in chronic lymphocytic leukaemia. PLoS One. 2015 Mar 18;10(3):e0118801. doi: 10.1371/journal.pone.0118801. eCollection 2015.

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Study Completion (Anticipated): April 1, 2013

Study Registration Dates

• First Submitted: May 8, 2009
• First Submitted That Met QC Criteria: June 8, 2009
• First Posted (Estimate): June 10, 2009

Study Record Updates

• Last Update Posted (Estimate): April 9, 2013
• Last Update Submitted That Met QC Criteria: April 5, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid
• Other Study ID Numbers: O-CLL1