Nilotinib in PH+, BCR-, ABL+ CML Patients

NCT01535391 | Completed Phase 3

• 2 other identifiers: CML08112011-002787-25
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 34

Brief Summary

This study is an open-label, multicentric, phase IIIb study of NILOTINIB administered orally twice daily for 24 months and indefinitely if it is in the interest of the patient. The primary objective of the trial is to evaluate the efficacy of nilotinib, 300 mg twice daily with dose increase to 400 mg twice daily in case of suboptimal response or failure (excluding patients who will fail for progression to ABP), in a population of patients with Ph-positive, BCR-ABL positive CML in early CP.

Conditions

Chronic Myeloid Leukemia

Keywords

Chronic Myeloid Leukemia,; Nilotinib,; Philadelphia positive,; BCR-ABL+; Early chronic phase

Outcome Measures

Primary Outcomes (1)

• Complete molecular response

  To assess the complete molecular response (CMR4) rate at 24 months of treatment. For the purpose of this protocol, CMR is defined as a negative results of quantitative RT-PCR for BCR-ABL transcripts in a peripheral blood sample of at least 10 ml with a minimum sensitivity of 1:10,000, that corresponds to at least a 4-log reduction (hence, CMR4)

  At 24 months of treatment

Secondary Outcomes (10)

• Toxicity

  At three years from study entry

• Compliance

  At 3 years from study entry

• The complete cytogenetic response (CCgR) rate

  At 3, 6, 12, 18 and 24 months from study entry

• The rate and the degree of molecular response

  At 3, 6, 12, 18 and 24 months from study entry

• The time to CCgR, the time to MMR and the time to CMR

  baseline

Interventions

Nilotinib DRUG

Administered orally at the dose of 300 mg twice daily (total daily dose 600 mg daily) for 24 months (study core), and indefinitely if it is in the interest of the patient (the drug will be given free-of-charge after 24 months to all those patients achieving the CMR4 at 24 months and in absence of safety concerns). Nilotinib dose is increased to 400 mg BID in case of suboptimal response or failure (with the exception of patients who will fail for progression to ABP: in case of progression to ABP, the patient will not be treated with study drug and the choise of the treatment will be up to the physician).

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18
• Male or female patients with diagnosis of Ph+ and/or BCR-ABL+ CML
• Early chronic phase (within 6 months from diagnosis)
• Pretreatment with Hydroxyurea or Anagrelide for a duration of up to 3 months and/or pretreatment with Imatinib for up to 30 days are permitted
• Normal serum levels of potassium, magnesium, phosphorus, total calcium corrected for serum albumin or phosphorus, or correctable to within normal limits with supplements prior to the first dose of study medication
• Written informed consent prior to any study procedures being performed
• AST and ALT ≤ 2.5 x ULN or ≤ 5.0 x ULN if considered due to leukaemia
• Alkaline phosphatase ≤ 2.5 x ULN unless considered due to leukaemia
• Total direct bilirubin ≤ 1.5 x ULN, except know Mb. Gilbert
• Serum creatinine ≤ 1.5 x ULN

You may not qualify if:

• Known impaired cardiac function, including any of the following:
• LVEF \< 45%
• Complete left bundle branch block
• Right bundle branch block plus left anterior hemiblock, bifascicular block
• Use of a ventricular-paced pacemaker
• Congenital long QT syndrome
• History of or presence of clinically significant ventricular or atrial tachyarrhythmias
• Clinically significant resting bradycardia (\<50 beats per minute)
• QTc\>450 msec on screening ECG. If QTc \> 450 msec and electrolytes are not within normal ranges before Nilotinib dosing, electrolytes should be corrected and then the patient rescreened for QTc criterion.
• Myocardial infarction within 12 months prior to starting study drugs
• Other clinical significant heart disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension)
• Serum lipase and amylase \> 1.5 x ULN (upper limit of normal) or history of acute (i.e., within 1 year of starting study medication) or chronic pancreatitis
• Other concurrent uncontrolled medical conditions (e.g., uncontrolled diabetes, active or uncontrolled infections, acute or chronic liver and renal disease) that could cause unacceptable safety risks or compromise compliance with the protocol
• Impaired gastrointestinal function or disease that may alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting and diarrhea, malabsorption syndrome, small bowel resection or gastric by-pass surgery)
• Concomitant medications with potential QT prolongation (see link for complete list: http://www.torsades.org/medical-pros/drug-lists/printable-drug-list.cfm)

Sponsors & Collaborators

• Gruppo Italiano Malattie EMatologiche dell'Adulto: lead

Study Sites (34)

Azienda Ospedaliera Nuovo Ospedale "Torrette"

Ancona, Italy

Location

S.G. Moscati Hospital

Avellino, Italy

Location

Azienda Ospedaliera Di Bologna Policlinico S. Orsola - Malpighi

Bologna, 40138, Italy

Location

USD Trapianti di midollo per adulti - Cattedra di Ematologia - Università degli Studi di Brescia

Brescia, 25123, Italy

Location

Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"

Catania, Italy

Location

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

Catanzaro, Italy

Location

Sezione di Ematologia e Fisiopatologia delle Emostasi - Azienda Ospedaliera - Arcispedale S. Anna

Ferrara, Italy

Location

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

Foggia, Italy

Location

Clinica Ematologica - DiMI - Università degli Studi di Genova

Genova, Italy

Location

Divisione Ematologia 1 - Azienda Ospedaliera Universitaria "San Martino"

Genova, Italy

Location

U.O. di Ematologia- Ospedale dell'Angelo - Mestre

Mestre, Italy

Location

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

Milan, Italy

Location

Centro Oncologico Modenese - Dipartimento di Oncoematologia

Modena, Italy

Location

Università degli Studi di Padova - Ematologia ed Immunologia Clinica

Padua, Italy

Location

Ospedale Cervello

Palermo, 90146, Italy

Location

Azienda Ospedaliera Universitaria - Policlinico Paolo Giaccone

Palermo, Italy

Location

Div. di Ematologia di Muraglia -CTMO Ospedale San Salvatore

Pesaro, Italy

Location

Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza

Piacenza, 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

IRCCS Centro di riferimento Oncologico di Basilicata

Rionero in Vulture, Italy

Location

Complesso Ospedaliero S. Giovanni Addolorata

Roma, Italy

Location

Pronto Soccorso e Accettazione Ematologica - Dipartimento Biotecnologie Cellulari ed Ematologia - Università degli Studi di Roma "Sapienza"

Roma, Italy

Location

U.O.C. Ematologia Ospedale S. Eugenio

Roma, Italy

Location

Università degli Studi Policlinico di Tor Vergata

Roma, Italy

Location

Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Italy

Location

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

Siena, Italy

Location

U.O.C. di Ematolgia - A.O. " SS Annunziata" - P.O. S.G. Moscati

Taranto, Italy

Location

SCDO Ematologia 2 AOU S.Giovanni Battista

Torino, Italy

Location

Azienda USL 9 Treviso - U.O. di Ematologia

Treviso, 31100, Italy

Location

Clinica Ematologica - Policlinico Universitario

Udine, Italy

Location

Università degli Studi di Verona - A. O. - Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi

Verona, Italy

Location

Related Publications (1)

• Castagnetti F, Breccia M, Gugliotta G, Martino B, D'Adda M, Stagno F, Carella AM, Avanzini P, Tiribelli M, Trabacchi E, Visani G, Gobbi M, Salvucci M, Levato L, Binotto G, Capalbo SF, Bochicchio MT, Soverini S, Cavo M, Martinelli G, Alimena G, Pane F, Saglio G, Rosti G, Baccarani M; GIMEMA CML Working Party. Nilotinib 300 mg twice daily: an academic single-arm study of newly diagnosed chronic phase chronic myeloid leukemia patients. Haematologica. 2016 Oct;101(10):1200-1207. doi: 10.3324/haematol.2016.144949. Epub 2016 Jul 28.

  PMID: 27470600 DERIVED

Related Links

• GIMEMA Foundation website

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

nilotinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Gianantonio Rosti

  Dpt of Hematology and Oncology, "Seràgnoli", Sant'Orsola-Malpighi. University Hospital of Bologna

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2012
• First Posted: February 17, 2012
• Study Start: January 1, 2012
• Primary Completion: November 1, 2014
• Study Completion: April 27, 2018
• Last Updated: August 6, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (34)