Clinical-biological Characteristics and Outcome of Chronic Lymphocytic Leukemia Under Ibrutinib-named Patient Program

NCT ID: NCT02582320

Last Updated: 2021-09-13

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 264 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2018-10-03

Brief Summary

This is a retrospective observational study aimed at describing the characteristics and outcome of CLL patients included in the NPP in Italy in a period of time ranging from the start of the NPP until November, 30th 2014. A longitudinal survey will be carried out by collecting data of patients who received at least 1 dose of Ibrutinib. All patients will be observed for at least 12 months from the treatment start.

Detailed Description

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. The disease is characterized by the progressive accumulation of phenotypically mature malignant B lymphocytes, primarily in the peripheral blood, bone marrow, and lymph nodes. Over the last 10-15 years several biological prognostic markers have been identified, starting from the immunoglobulin gene mutational analysis to CD38, ZAP70, CD49d expression, and many others. The very recent discovery of several new genes that carry point mutations in CLL, including NOTCH1, SF3B1 and BIRC3, has added more markers that seem to correlate with resistance to treatment and with transformation into Richter syndrome. A large number of chemoimmunotherapy regimens are currently considered for the treatment of CLL patients.

NPP program The Named Patient Program (NPP) is a program intended to provide early access to ibrutinib in Italy. This program is specifically for patients who have relapsed or refractory chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL), mantle cell lymphoma.

Rationale In patients with CLL Ibrutinib, given as single agent has shown marked activity and a good safety profile. Data from patients treated with ibrutinib outside a controlled clinical trial within a National Patient Program (NPP) could give additional information about the clinical use, treatment duration, efficacy, and toxicity of ibrutinib given to CLL patients in a real life context.

Conditions

Chronic Lymphocytic Leukemia

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Study patients

Patients with Relapsed or refractory CLL or 17p deleted CLL fulfilling the eligibility criteria required by the Named Patient Program (NPP) who received at least 1 dose of Ibrutinib 420 mg daily before November, 30th 2014.

Ibrutinib

Intervention Type: DRUG

A longitudinal survey will be carried out by collecting data of patients who received at least 1 dose of Ibrutinib. All patients will be observed for at least 12 months from the treatment start.

Interventions

Ibrutinib

A longitudinal survey will be carried out by collecting data of patients who received at least 1 dose of Ibrutinib. All patients will be observed for at least 12 months from the treatment start.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients ≥18 years of age.

2. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.

3. A minimum of one prior line of systemic chemotherapy, chemo-immunotherapy, or an alemtuzumab-based regimen, consisting of at least two cycles of therapy.

4. Relapsed or refractory CLL with one or more of the following criteria:

• Presence of deletion of the short-arm of chromosome 17 (ie 17p deletion).
• Relapsed: Failed two or more previous treatments, at least one with a purine analogue such as fludarabine.
• Relapsed: Progression-free interval of less than 24 months from completing treatment with a nucleoside analogue, or bendamustine-containing regimen in combination with an anti-CD20 monoclonal antibody such as rituximab.
• Refractory: Failure to respond to a prior chemotherapy-based treatment, stable disease, or disease progression while on treatment.

5. Patient has active CLL requiring treatment as defined by the IWCLL 2008 criteria. A minimum of one of the following criteria is required:

• Evidence of progressive marrow failure, as manifested by the development of, or worsening of, anemia or thrombocytopenia.
• Massive (at least 6 cm below the left costal margin), progressive, or symptomatic splenomegaly.

c. Massive nodes (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 of less than 6 months (which may be extrapolated). For patients with initial blood lymphocyte counts of less than 30 x 109/L (30,000/mL), lymphocyte doubling time should not be used as a single parameter to define indication for treatment. Factors contributing to lymphocytosis or lymphadenopathy other than CLL (e.g., infections) should be excluded.
• Constitutional symptoms, defined as 1 or more of the following disease-related symptoms or signs:

i. Unintentional weight loss >10% within the previous 6 months prior to screening.

ii. Significant fatigue (inability to work or perform usual activities). iii. Fever higher than 38.0°C for 2 or more weeks without evidence of infection.

iv. Night sweats for more than 1 month without evidence of infection.

6. Haematology values within the following parameters:

• Absolute neutrophil count (ANC) of ≥0.75 x109/L independent of growth factor support.
• Platelet count of ≥30 x109/L independent of platelet support.

7. Biochemical values within the following limits:

• Serum creatinine ≤2 times the upper limit of normal (ULN) or estimated glomerular filtration rate (GFR [Crockcoft-Gault]) ≥30 mL/minute.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times ULN.
• Total bilirubin ≤1.5 times ULN (unless the bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin) for whom the upper limit of serum bilirubin is 3 mg/dl.

8. No problems to swallowing regularly capsules.

9. Agreed to practice a highly effective method of birth control during and after participation in the NPP if they are of childbearing potential and sexually active.

10. Signed informed consent document (if feasible) indicating that they understand the purpose of the study, they agree to give complete access to their medical records.

Exclusion Criteria

1. Previous treatment with ibrutinib or participation to an ibrutinib clinical trial (ibrutinib or comparator arm).

2. Eligible to participate in a currently recruiting ibrutinib clinical trial.

3. Previously received ibrutinib as part of a clinical trial.

4. Previously received a Bruton's tyrosine kinase (BTK) inhibitor other than ibrutinib.

5. Currently enrolled in an interventional clinical trial.

6. Currently receiving chemotherapy, anticancer immunotherapy, or experimental therapy.

7. Currently recovering from acute toxicities of prior treatment for CLL.

8. Received stem cell transplantation within the past 6 months.

9. Evidence of graft-versus-host disease and/or requires immunosuppressant therapy.

10. Major surgery within the past 4 weeks or a major wound that has not fully healed.

11. History of human immunodeficiency virus (HIV) or active infection with Hepatitis C or B.

12. Ongoing uncontrolled active systemic infection.

13. Uncontrolled autoimmune haemolytic anemia (AIHA).

14. Uncontrolled idiopathic thrombocytopenic purpura (ITP).

15. Central nervous system leukemia/lymphoma or Richter's transformation.

16. Diagnosed or treated for another malignancy, other than CLL, except for:

• Malignancy treated with curative intent and with no known active disease present for ≥3 years prior to entering this named patient program and considered to be at low risk for recurrence.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated cervical carcinoma in situ without evidence of disease.

17. Stroke within the past 6 months.

18. Intracranial haemorrhage within the past 6 months.

19. Requires anticoagulation with warfarin or equivalent vitamin K antagonist (e.g. phenprocoumon).

20. Requires treatment with a strong CYP3A inhibitor.

21. Clinically significant cardiovascular disease such as:

• Uncontrolled or symptomatic arrhythmias.
• Congestive heart failure.
• Myocardial infarction within the past 6 months.
• Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification.

22. Patient has any life-threatening illness, medical condition, clinically significant.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gruppo Italiano Malattie EMatologiche dell'Adulto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roberto Foà

Role: STUDY_CHAIR

Policlinico Umberto I, Hematology Department.

Locations

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

Ascoli Piceno, , Italy

U.O.C di Ematologia P.O. "S.Giuseppe Moscati" - 2° piano

Aversa, , Italy

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

Bari, , Italy

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

Bologna, , Italy

Spedali Civili - Brescia - Azienda Ospedaliera - U.O. Ematologia

Brescia, , Italy

Divisione di Ematologia Ospedale A. Perrino

Brindisi, , Italy

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

Cagliari, , Italy

US Dipartimentale - Centro per le malattie del sangue - Ospedale Civile - S.Giacomo

Castelfranco Veneto, , Italy

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

Catanzaro, , Italy

U.O. di Medicina Interna - ASUR Marche 8 - Ospedale Civile

Civitanova Marche, , Italy

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

Cona, , Italy

Unità di Ricerca e di Malattie del sangue - Ematologia San Luca Vecchio Pad. 16 - 1° Piano

Florence, , Italy

IRCCS_AOU San Martino-IST.Clinica Ematologica

Genova, , Italy

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

Lecce, , Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico UOC Oncoematologia- Padiglione Marcora 2° piano

Milan, , Italy

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

Milan, , Italy

U.O. Ematologia e Trapianto di MIdollo - Ist.Scientifico Ospedale San Raffaele

Milan, , Italy

Unità Trapianto di Midollo Ist. Nazionale Tumori

Milan, , Italy

UO Ematologia - AOU Policlinico di Modena

Modena, , Italy

Ospedale San Gennaro - ASL Napoli 1

Napoli, , Italy

S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro

Novara di Sicilia, , Italy

Università degli Studi di Padova - Ematologia ed Immunologia Clinica

Padua, , Italy

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

Pagani, , Italy

Cattedra di Ematologia CTMO Università degli Studi di Parma

Parma, , Italy

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

Pavia, , Italy

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

Perugia, , Italy

U.O. Ematologia Clinica - Azienda USL di Pescara

Pescara, , Italy

Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale G. da Saliceto

Piacenza, , Italy

Ematologia - Ospedale San Carlo

Potenza, , Italy

Dipartimento Oncologico - Ospedale S.Maria delle Croci

Ravenna, , Italy

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

Reggio Calabria, , Italy

Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova

Reggio Emilia, , Italy

Ospedale "Infermi"

Rimini, , Italy

U.O.C. Ematologia - IRCCS Centro oncologico della Basilicata

Rionero in Vulture, , Italy

S.C. di Ematologia e Trapianti - I.F.O. Istituto Nazionale Tumori Regina Elena

Roma, , Italy

U.O.C. Ematologia - Ospedale S.Eugenio

Roma, , Italy

U.O.S.A. Ematologia ASL RMA Presidio Nuovo Regina Margherita

Roma, , Italy

Università Cattolica del Sacro Cuore - Policlinico A. Gemelli

Roma, , Italy

Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia

Roma, , Italy

Policlinico Umberto I, Hematology Department - Sapienza

Rome, , Italy

Sezione di Ematologia Cancer Center Humanitas

Rozzano, , Italy

Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, , Italy

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

Siena, , Italy

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

Terni, , Italy

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

Torino, , Italy

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

Torino, , Italy

ULSS N.6 Osp. S. Bortolo

Vicenza, , Italy

Countries

Italy

Related Links

http://www.gimema.it

GIMEMA Foundation website

Other Identifiers

LLC1415

Identifier Type: -

Identifier Source: org_study_id