Sustained Treatment-free Remission in BCR-ABL+ Chronic Myeloid Leukemia

NCT02602314 | Unknown Phase 4 DMC

• 1 other identifier: CML1415
• Study Type: interventional
• Target: 450
• Locations: 2 countries
• Sites: 82

Brief Summary

The study will investigate in newly diagnosed CP-CML patients the efficacy of NIL frontline therapy vs IM followed by switch to NIL in the case of absence of optimal response as defined by the ELN criteria.

Conditions

Chronyc Myeloid Leukemia

Keywords

Chronic myeloid leukemia; Nilotinib; Imatinib

Outcome Measures

Primary Outcomes (2)

• Number of of patients with molecular response

  At 24 months from study entry

• Number of patients who remain in sustained treatment free remission, without molecular relapse

  After 12 months after entering the treatment-free-remission (TFR) phase

Secondary Outcomes (6)

• Number of patients with molecular response

  4 years after study entry

• Number of patiens in progression-free survival

  5 years after study entry

• Number of patients with major molecular response

  At 1, 2, 3 and 4 years from study entry

• Number of toxic events

  At 5 years from study entry

• Number of patients who discontinue treatment

  At 5 years from study entry

Study Arms (2)

Imatinib + Nilotinib

EXPERIMENTAL

Drug: Imatinib; Drug: Nilotinib

Nilotinib

EXPERIMENTAL

Drug: Nilotinib

Interventions

Imatinib DRUG

Imatinib + Nilotinib

Nilotinib DRUG

Imatinib + Nilotinib; Nilotinib

Eligibility Criteria

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

You may qualify if:

• Patients with a confirmed diagnosis of BCR/ABL+ CML in chronic phase
• Documented chronic phase CML must meet all the following criteria:
• \< 15% blasts in peripheral blood \< 30% blasts plus promyelocytes in peripheral blood \< 20% basophils in the peripheral blood
• x 109/L (≥ 100,000/mm3) platelets
• Age ≥18
• ECOG performance status of 0-2
• Evidence of typical BCR-ABL transcripts which are amenable to standardized RQ-PCR
• Adequate end organ function as defined by:
• Total bilirubin \< 1.5 x ULN (ULN = upper limit of normal in a local institution lab).
• Does not apply to patients with isolated hyperbilirubinemia (e.g., Gilbert's disease) grade \< 3 SGOT (AST) and SGPT (ALT) ≤ 3 x ULN Serum amylase and lipase ≤ 2 x ULN Alkaline phosphatase ≤ 2.5 x ULN Serum creatinine \< 1.5 x ULN
• Having completed the QoL baseline evaluation (i.e., before randomization)
• Written informed consent prior to any study procedures.

You may not qualify if:

• Expression of any atypical BCR-ABL transcripts, instead of the classical P210-encoding type with the e13a2 or the e14a2 junction at screening.
• Previous treatment with BCR-ABL inhibitors for a period longer than 1 month.
• Previous anticancer agents (hydroxyurea, anagrelide, interferon) for CML for a time longer than three months.
• Poorly controlled diabetes mellitus (defined as HbA1c \>8%).
• Prior documented history of coronary heart disease, including myocardial infarction, coronary bypass, coronary stent, and symptomatic angina:
• LVEF \<45% or below the institutional lower limit of the normal range (whichever ishigher) Complete left bundle branch block Right bundle branch block plus left anterior or posterior hemiblock Use of a ventricular-paced pacemaker Congenital long QT syndrome or a known family history of long QT syndrome History of or presence of clinically significant ventricular or atrial tachyarrhythmias
• Atrial fibrillation or flutter
• Clinically significant resting bradycardia (\< 50 beats per minute)
• QTc \> 450 msec on the average of three serial screening ECGs (using the QTcF formula). If QTcF \> 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and the patient re-tested History or clinical signs of myocardial infarction within 12 months of study entry History of unstable angina within 12 months of study entry Other clinically significant heart disease (e.g. congestive heart failure)
• Uncontrolled hypertension is not a heart disease.
• History of peripheral arterial occlusive disease.
• History of acute pancreatitis within 12 months of study entry, or a past medical history of chronic pancreatitis.
• Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers which cannot be either discontinued or switched to a different medication prior to starting study drug.
• Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and for which cannot be either safely discontinued or switched to a different medication prior to starting study drug.

Sponsors & Collaborators

• Gruppo Italiano Malattie EMatologiche dell'Adulto: lead

Study Sites (82)

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

Alessandria, Italy

Location

Azienda Ospedaliero - Universitaria Ospedali Riuniti Umberto I - G.M. Lancisi G. Salesi

Ancona, Italy

Location

Area Vasta N. 5 Ascoli Piceno - S. Benedetto Del Tronto, Presidio Ospedaliero Av5 Osp. Gen. Prov.Le "C.G.Mazzoni" - Uoc Ematologia

Ascoli Piceno, Italy

Location

Asl Di Asti, Ospedali Riuniti - Presidio Ospedaliero Cardinal G. Massaia - Sc Oncologia

Asti, Italy

Location

Ao Di Rilievo Nazionale E Di Alta Specialità "San Giuseppe Moscati" - Avellino - Uoc Ematologia Con Unità Di Trapianto

Avellino, Italy

Location

Aou Consorziale Policlinico - Bari - Uo Ematologia Con Trapianto

Bari, Italy

Location

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

Bari, Italy

Location

Asl Della Provincia Di Barletta, Andria, Trani, Ospedale "Mons. Dimiccoli" - Barletta - Uo Ematologia

Barletta, Italy

Location

Ematologia Torre 6 piano 4 - ASST Papa Giovanni XXIII

Bergamo, Italy

Location

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

Bologna, Italy

Location

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

Brescia, Italy

Location

ASL N.8 -Ospedale A. Businco

Cagliari, Italy

Location

Cagliari CTMO - Ematologia - Ospedale "Binaghi"

Cagliari, Italy

Location

Gemelli Molise - Campobasso - Uosd Onco-Ematologia

Campobasso, Italy

Location

U.O.C. Oncoematologia - Istituto Oncologico Veneto Irccs, Presidio Ospedaliero S. Giacomo Apostolo

Castelfranco Veneto, Italy

Location

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

Catania, Italy

Location

Ao Di Catanzaro "Pugliese-Ciaccio", Presidio Ospedaliero "Ciaccio - de Lellis" - Ematologia

Catanzaro, Italy

Location

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

Civitanova Marche, Italy

Location

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

Cona, Italy

Location

Ao Di Cosenza, Presidio Ospedaliero Annunziata - Uoc Ematologia

Cosenza, Italy

Location

S.C. Ematologia ASO S. Croce e Carle

Cuneo, Italy

Location

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

Florence, Italy

Location

Aou Ospedali Riuniti - Foggia - Uoc Ematologia

Foggia, Italy

Location

Irccs Aou San Martino - Genova - Uo Ematologia E Trapianti

Genova, Italy

Location

IRCCS_AOU San Martino-IST.Clinica Ematologica

Genova, Italy

Location

Asl Latina, Presidio Ospedaliero Nord - Ospedale Santa Maria Goretti - Uoc Ematologia

Latina, Italy

Location

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

Lecce, Italy

Location

I.R.S.T. Srl Irccs - Meldola - Sc Oncologia Medica

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

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

Mestre, Italy

Location

Fondazione Irccs "Istituto Nazionale Tumori" - Milano - Sc Ematologia

Milan, Italy

Location

Fondazione Irccs Ca' Granda, Ospedale Maggiore Policlinico - Milano - Ematologia - Padiglione Marcora

Milan, Italy

Location

UO Ematologia - AOU Policlinico di Modena

Modena, Italy

Location

Asl Napoli 1 Centro, Presidio Ospedaliero Ascalesi - Ospedale S.Maria Di Loreto Nuovo

Napoli, Italy

Location

Azienda Ospedaliera di Rilievo Nazionale A. Cardarelli

Napoli, Italy

Location

Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia

Napoli, Italy

Location

Ospedale San Gennaro - ASL Napoli 1

Napoli, Italy

Location

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

Novara, Italy

Location

U.O. CTMO Ematologia - Osp. S. Francesco

Nuoro, Italy

Location

Dip. di Scienze Cliniche e Biologiche - Ospedale S. Luigi Gonzaga-Medicina Interna 2

Orbassano, Italy

Location

Aou Di Padova - Uo Ematologia

Padua, Italy

Location

Asl Salerno, Presidio Ospedaliero Tortora Pagani - Ematologia

Pagani, Italy

Location

Ospedali Riuniti "Villa Sofia-Cervello"

Palermo, Italy

Location

U.O. di Ematologia con trapianto - Centro di Riferimento Regionale per le coagulopatie rare nel bambino e nell'adulto Dipart. Biomedico di Medicina Interna - A.U. Policlinico "Paolo Giaccone"

Palermo, Italy

Location

Aou Di Parma - Sc Ematologia E Centro Trapianti Midollo Osseo

Parma, Italy

Location

Div. di Ematologia di Muraglia - CTMO Ospedale San Salvatore

Pesaro, Italy

Location

Asl Pescara, Presidio Ospedaliero 'Spirito Santo' - Uoc Ematologia Clinica

Pescara, Italy

Location

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

Piacenza, Italy

Location

Az.Ospedaliera S.G.Moscati

Potenza, 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

Ausl Della Romagna, Ospedale "Infermi" - Rimini - Uo Ematologia

Rimini, Italy

Location

Asl Roma 2, Ospedale S. Eugenio- Ospedale S.Eugenio - Uoc Ematologia

Roma, Italy

Location

Az. Ospedaliera "Sant' Andrea"-Università la Sapienza Seconda Facoltà di Medicina e Chirurgia

Roma, Italy

Location

Divisione Ematologia - Università Campus Bio-Medico

Roma, Italy

Location

Università Cattolica del Sacro Cuore - Policlinico A. Gemelli

Roma, Italy

Location

UOC 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

Rome, Italy

Location

Unità Operativa di Oncologia Giovanni Paolo II "Vito Fazzi"

Rossano, Italy

Location

Aulss 5 Polesana, Presidio Ospedaliero Di Rovigo - Uosd Ematologia

Rovigo, Italy

Location

Aou "San Giovanni Di Dio E Ruggi D'Aragona" - Salerno - Uoc Ematologia E Trapianti Di Cellule Staminali Emopoietiche

Salerno, Italy

Location

Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Italy

Location

Ematologia - Dipartimento di Medicina Clinica e Sperimentale

Sassari, Italy

Location

Ospedale Di Sassuolo Spa - Ematologia

Sassuolo, Italy

Location

Aou Senese - Uoc Ematologia E Trapianti

Siena, Italy

Location

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

Terni, Italy

Location

Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia - Università Degli Studi Di Torino

Torino, Italy

Location

Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia 2

Torino, Italy

Location

Ospedale Mauriziano Umberto I - Torino - Scdu Ematologia

Torino, Italy

Location

Unità Operativa Di Ematologia - Presidio Ospedaliero Di Treviso - Azienda Ulss N.2 Marca Trevigiana

Treviso, Italy

Location

Clinica Ematologica-Centro Trapianti e Terapie cellulari Azienda Ospedaliero-Universitaria, Udine

Udine, Italy

Location

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

Verona, Italy

Location

Aulss 8 Berica - Ospedale Di Vicenza - Uoc Ematologia

Vicenza, Italy

Location

ULSS N.6 Osp. S. Bortolo

Vicenza, Italy

Location

Meander Mc - Paesi Bassi

Amersfoort, Netherlands

Location

Vumc - Paesi Bassi

Amsterdam, Netherlands

Location

Reinier de Graaf Gasthuis

Delft, Netherlands

Location

A. Schweitzer Zh, Dordwijk - Paesi Bassi

Dordrecht, Netherlands

Location

Zuyderland Medical Center - Paesi Bassi

Heerlen, Netherlands

Location

Spaarne Ziekenhuis - Paesi Bassi

Hoofddorp, Netherlands

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Imatinib Mesylate; 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

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Fabrizio Pane

  Università Federico II of Naples

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2015
• First Posted: November 11, 2015
• Study Start: November 11, 2016
• Primary Completion: February 1, 2023
• Study Completion: February 1, 2024
• Last Updated: January 20, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (76); NL (6)