Phase 2 Study to Assess Activity & Safety of Front-line Ibrutinib + Rituximab in Unfit Chronic Lymphocytic Leukemia

NCT02232386 | Completed Phase 2

• 2 other identifiers: LLC11142014-002714-23
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 36

Brief Summary

The present study aims at evaluating whether treatment with two different drugs, Ibrutinib and Rituximab is both efficient and safe for newly diagnosed patients with chronic lymphocytic leukemia.

Conditions

Chronic Lymphocyte Leukemia; Adult Patients

Keywords

Chronic lymphocyte leukemia; Adults; Ibrutinib

Outcome Measures

Primary Outcomes (1)

• Number of patients on progression-free survival

  To estimate Progression-Free Survival (PFS) at 12 months in patients treated with Ibrutinib plus Rituximab combination in unfit patients with CLL.

  At 12 months from treatment start

Secondary Outcomes (13)

• Number of patients in complete response (CR) or partial response (OR)

  At the end of induction therapy, that is, 7 months from treatment start

• Number of patients in CR

  At the end of induction therapy, that is, at 7 months from treatment start

• Number of negative minimal residual disease CRs

  At the end of induction therapy, that is, at 7 months from treatment start

• Number of days from treatment discontinuation to new treatment restart.

  At the end of the study, that is, 90 months from treatment start

• Number of patients in event-free survival

  At 36 months from treatment start

Study Arms (1)

Treatment

EXPERIMENTAL

Ibrutinib (PCI-32765) 420 mg (3 x 140 mg capsules) will be administered orally once daily. The first dose will be delivered in the clinic on Day 1, after which subsequent dosing is typically on an outpatient basis. Treatment duration with Ibrutinib will be based on what comes first of the following three options: * Treatment until progression or toxicity * Treatment until MRD negativity for 6 months * Treatment for 6 years. Rituximab 375 mg/m2 iv. Month 1: day 1 of weeks 1, 2, 3, 4; months 2-6: day 1of week 1.

Drug: Ibrutinib; Drug: Rituximab

Interventions

Ibrutinib DRUG

Ibrutinib (PCI-32765) 420 mg (3 x 140 mg capsules) will be administered orally once daily. The first dose will be delivered in the clinic on Day 1, after which subsequent dosing is typically on an outpatient basis.

Treatment

Rituximab DRUG

Rituximab 375 mg/m2 iv. Month 1: day 1 of weeks 1, 2, 3, 4; months 2-6: day 1of week 1.

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older.
• Diagnosis of CLL meeting IWCLL criteria.
• The diagnosis of CLL requires a history of lymphocytosis with a B-lymphocyte count ≥5,000/μL. Prolymphocytes may comprise no more than 55% of blood lymphocytes.
• Active disease meeting at least 1 of the following IWCLL 2008 criteria for requiring treatment:
• Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia or thrombocytopenia.
• Massive (ie, at least 6 cm below the left costal margin), progressive, or symptomatic splenomegaly.
• Massive nodes (ie, at least 10 cm in longest diameter), progressive, or symptomatic lymphadenopathy.
• Progressive lymphocytosis with an increase of more than 50% over a 2-month period or a lymphocyte doubling time (LDT) of less than 6 months (which may be extrapolated). Lymphocyte doubling time can be obtained by linear regression extrapolation of ALCs obtained at intervals of 2 weeks over an observation period of 2 to 3 months. For patients with initial blood lymphocyte counts of less than 30 x 109/L (30,000/μL), LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infections) should be excluded.
• Constitutional symptoms, defined as 1 or more of the following disease-related symptoms or signs:
• Unintentional weight loss \>10% within the previous 6 months prior to screening
• Significant fatigue (inability to work or perform usual activities)
• Fevers higher than 38.0°C for 2 or more weeks without evidence of infection; or
• Night sweats for more than 1 month without evidence of infection
• Measurable nodal disease by computed tomography (CT). Measurable nodal disease is defined as at least one lymph node \>1.5 cm in longest diameter in a site that has not been previously irradiated. An irradiated lesion may be assessed for measurable disease only if there has been documented progression in that lesion since radiotherapy has ended.
• No prior treatment.

You may not qualify if:

• Any significant concurrent, uncontrolled medical condition or organ system dysfunction and/or laboratory abnormality or psychiatric disease which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk or prevent the subject from signing the informed consent form.
• Pregnant or lactating females
• Known presence of alcohol and/or drug abuse.
• Any potential subject who meets any of the following criteria will be excluded from participating in the study.
• Major surgery within 4weeks of randomization.
• Uncontrolled autoimmune hemolytic anemia or thrombocytopenia.
• Known central nervous system lymphoma.
• History of stroke or intracranial hemorrhage within 6 months prior to randomization, or of a significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae.
• Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) in any moment of the study.
• Requires treatment with strong CYP3A inhibitors.
• Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association
• Vaccinated with live, attenuated vaccines within 4 weeks of randomization.
• Known history of human immunodeficiency virus (HIV) positive serology for HIV; active Hepatitis B Virus infection or positive serology for Hepatitis B (HBV) defined as a positive test for HBsAg and HBV-DNA; active Hepatitis C or HCV-RNA positive; any uncontrolled active systemic infection requiring intravenous (IV) antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection; history of tuberculosis within the last five years or recent exposure to tuberculosis equal to or less than 6 months.
• Richter's syndrome (RS), concomitant or past 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.

Sponsors & Collaborators

• Gruppo Italiano Malattie EMatologiche dell'Adulto: lead

Study Sites (36)

S.O.C. di Ematologia - Azienda Ospedaliera - SS. Antonio e Biagio e Cesare Arrigo

Alessandria, Italy

Location

U.O.C. Ematologia e Terapia Cellulare - Ospedale "C. e G. Mazzoni" di Ascoli Piceno

Ascoli Piceno, Italy

Location

S.O.C. di Medicina Interna B - Ospedale - Cardinal Massaia di Asti

Asti, Italy

Location

UO Ematologia con trapianto-Università degli Studi di Bari Aldo Moro

Bari, Italy

Location

Istituto di Ematologia "Lorenzo e A. Seragnoli" - Università degli Studi di Bologna - Policlinico S. Orsola - Malpighi

Bologna, Italy

Location

ASL N.8 - Ospedale "A. Businco" - Struttura Complessa di Ematologia e CTMO

Cagliari, Italy

Location

U.O.C. di Onco-Ematologia - Centro di Ricerca e Formazione ad Alta tecnologia nelle Scienze Biomediche

Campobasso, Italy

Location

Unità di Onco-Ematologia - Azienda Ospedaliera - Garibaldi

Catania, Italy

Location

Azienda Ospedaliera Pugliese Ciaccio - Presidio Ospedaliero A.Pugliese - Unità Operativa di Ematologia

Catanzaro, Italy

Location

Azienda Ospedaliero Universitaria Arcispedale Sant'Anna Dipartimento di Scienze Mediche Sezione di Ematologia e Fisiopatologia dell'Emostasi

Cona, Italy

Location

U.O. Ematologia - P.O. Annunziata - A.O. di Cosenza

Cosenza, Italy

Location

Struttura Complessa di Ematologia Ospedali Riuniti Foggia - Azienda Ospedaliero-Universitaria

Foggia, Italy

Location

IRCCS_AOU San Martino-IST-Ematologia 1-Monoblocco 11°piano- lato ponente

Genova, Italy

Location

ASL Le/1 P.O. Vito Fazzi - U.O. di Ematologia ed UTIE

Lecce, Italy

Location

Istituto Scientifico Romagnoli per lo Studio e la Cura dei Tumori- IRST

Meldola, Italy

Location

Azienda Ospedaliera Universitaria - Policlinico G. Martino Dipartimento di Medicina Interna - U.O. Messina

Messina, Italy

Location

Divisione di Ematologia - Azienda Ospedaliera Ospedali Riuniti "Papardo Piemonte"

Messina, Italy

Location

Ospedale Niguarda " Ca Granda" - SC Ematologia Blocco SUD, Ponti Est, Scala E, 4° piano

Milan, Italy

Location

UO Ematologia - AOU Policlinico di Modena

Modena, Italy

Location

.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro Gianluca Gaidano S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro Novara Davide Rossi S

Novara, Italy

Location

Università degli Studi di Padova - Ematologia ed Immunologia Clinica

Padua, Italy

Location

U.O. di Oncoematologia di Nocera Inferiore-plesso ospedaliero "A. Tortora" di Pagani del DEA Nocera-Pagani

Pagani, Italy

Location

Cattedra di Ematologia CTMO Università degli Studi di Parma

Parma, Italy

Location

S.C. Ematologia - Fondazione IRCCS Policlinico S. Matteo

Pavia, Italy

Location

Sezione di Ematologia ed Immunologia Clinica - Ospedale S.Maria della Misericordia

Perugia, Italy

Location

U.O. Ematologia Clinica - Azienda USL di Pescara

Pescara, Italy

Location

Dipartimento Oncologico - Ospedale S.Maria delle Croci

Ravenna, Italy

Location

Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"

Reggio Calabria, Italy

Location

Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova

Reggio Emilia, Italy

Location

Ospedale "Infermi"

Rimini, Italy

Location

Dipartimento di Biotecnologie Cellulari ed Ematologia - Università degli Studi "Sapienza" di Roma

Roma, Italy

Location

Università Cattolica del Sacro Cuore - Policlinico A. Gemelli

Roma, Italy

Location

U.O.C. Ematologia e Trapianti - A.O. Senese - Policlinico " Le Scotte"

Siena, Italy

Location

A.O. Santa Maria - Terni S.C Oncoematologia

Terni, Italy

Location

Dipartimento di Oncologia ed Ematologia S.C. Ematologia 2 A.O. Città della Salute e della Scienza di Torino San Giovanni Battista

Torino, Italy

Location

Divisione di Ematologia dell' Università degli Studi di Torino - "Città della Salute e della Scienza di Torino"

Torino, Italy

Location

Related Publications (1)

• Peragine N, De Propris MS, Intoppa S, Milani ML, Mauro FR, Cuneo A, Rigolin GM, Del Giudice I, Foa R, Guarini A. Early CD49d downmodulation in chronic lymphocytic leukemia patients treated front-line with ibrutinib plus rituximab predicts long-term response. Leuk Lymphoma. 2022 Dec;63(12):2982-2986. doi: 10.1080/10428194.2022.2105324. Epub 2022 Aug 1. No abstract available.

  PMID: 35913400 DERIVED

MeSH Terms

Interventions

ibrutinib; Rituximab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Francesca Mauro

  Policlinico Umberto I di Roma

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2014
• First Posted: September 5, 2014
• Study Start: March 2, 2015
• Primary Completion: April 1, 2018
• Study Completion: April 16, 2024
• Last Updated: January 16, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (36)