Nilotinib and Imatinib Mesylate in Treating Patients With Early Chronic Phase Chronic Myelogenous Leukemia

NCT ID: NCT00769327

Last Updated: 2022-01-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 129 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-09
• Study Completion Date: 2014-10-10

Brief Summary

RATIONALE: Nilotinib and imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well giving nilotinib together with imatinib mesylate works in treating patients with early chronic phase chronic myelogenous leukemia.

Detailed Description

OBJECTIVES:

Primary

• To assess the complete cytogenetic response rate at 12 months in patients with Philadelphia chromosome- and BCR-ABL-positive early chronic phase chronic myelogenous leukemia treated with nilotinib and imatinib mesylate.

Secondary

• To assess the complete cytogenetic response rate at 6 and 24 months in these patients.
• To assess the major and complete molecular response rate at 6, 12, and 24 months in these patients.
• To assess the frequency and the types of BCR-ABL kinase domain mutations at 24 months during and for 3 years after study treatment.
• To assess the rate of failures and the time to failure at 12, 24, and 60 months in these patients.
• To assess compliance, toxicity, and adverse events in these patients.
• To understand the relationship between response, gene expression profile, biomarkers, and drug plasma concentrations in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral nilotinib twice daily in months 1-3, 7-9, 13-15, and 19-21 and oral imatinib mesylate once daily in months 4-6, 10-12, 16-18, and 22-24. Treatment continues for 24 months in the absence of disease progression or unacceptable toxicity. Patients may be eligible to continue oral nilotinib and oral imatinib mesylate for up to another 36 months if it is in the interest of the patient.

Blood samples and bone marrow biopsies are collected periodically for cytogenetic response by chromosome banding analysis and FISH analysis; real-time quantitative PCR mutational analysis and single nucleotide polymorphism analysis of BCR-ABL transcripts; and gene expression profiling and correlative biomarker studies.

After completion of study therapy, patients are followed every 6 months for 3 years and then every 12 months for 5 years.

Conditions

Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

imatinib mesylate

Intervention Type: DRUG

nilotinib

Intervention Type: DRUG

cytogenetic analysis

Intervention Type: GENETIC

fluorescence in situ hybridization

Intervention Type: GENETIC

microarray analysis

Intervention Type: GENETIC

mutation analysis

Intervention Type: GENETIC

polymerase chain reaction

Intervention Type: GENETIC

polymorphism analysis

Intervention Type: GENETIC

laboratory biomarker analysis

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Cytologically and cytogenetically confirmed chronic myelogenous leukemia meeting the following criteria:

• Early chronic phase disease (< 6 months from diagnosis)
• Philadelphia chromosome-positive disease
• BCR-ABL-positive

PATIENT CHARACTERISTICS:

• WHO performance status 0-1
• ALT and AST = 2.5 times upper limit of normal (ULN) (5.0 times ULN if considered due to leukemia)
• Alkaline phosphatase = 2.5 times ULN (unless considered due to leukemia)
• Serum bilirubin = 1.5 times ULN
• Serum creatinine = 1.5 times ULN
• Serum amylase = 1.5 times ULN
• Serum lipase = 1.5 times ULN
• Normal serum levels of the following or correctable with supplements:

• Potassium
• Total calcium (corrected for serum albumin)
• Magnesium
• Phosphorus
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier method contraception during study and for up to 3 months following completion of study treatment
• No impaired cardiac function, including any of the following:

• LVEF < 45% by MUGA scan or echocardiogram
• Uncontrolled congestive heart failure
• Uncontrolled hypertension
• Uncontrolled angina pectoris
• Myocardial infarction within the past 12 months
• No significant electric heart abnormalities, including any of the following:

• History or active ventricular or atrial tachyarrhythmias
• Congenital long QT syndrome and/or QTc > 450 msec on screening ECG
• No history of acute (within one year) or chronic pancreatitis
• No impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• No acute or chronic liver or renal disease considered unrelated to leukemia
• No known diagnosis of HIV infection
• No other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes, active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol
• No other primary malignancy that is currently clinically significant or requires active intervention

PRIOR CONCURRENT THERAPY:

• More than 2 weeks since prior major surgery and recovered
• More than 30 days since prior imatinib mesylate, with a washout period of ≥ 7 days
• More than 4 weeks since prior investigational drug
• No prior hematopoietic stem cell transplantation
• No concurrent therapeutic coumarin derivates (i.e., warfarin, acenocoumarol, phenprocoumon)
• No concurrent medications that would prolong the QT interval
• No concurrent chemotherapy, investigational agents, radiotherapy, or biologic therapy
• Prior treatment with hydroxyurea or anagrelide allowed

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 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

Michele Baccarani, MD

Role: PRINCIPAL_INVESTIGATOR

Gruppo Italiano Malattie EMatologiche dell'Adulto

Locations

Centro Oncologico Basilicata

Rionero in Vulture, Potenza, Italy

Ospedale Civile Alessandria

Alessandria, , Italy

Dipartimento Area Medica P.O.

Ascoli Piceno, , Italy

S.G. Moscati Hospital

Avellino, , Italy

Unità Operativa Ematologia 1 - Università degli Studi di Bari

Bari, , Italy

Ospedali Riuniti di Bergamo

Bergamo, , Italy

Ist.Ematologia e Oncologia Medica L.e A. Seragnoli

Bologna, , Italy

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

Cagliari, , Italy

Ctc U.O Di Ematologia Con Trapianto Di Midollo Osseo - Catania

Catania, , Italy

Unità di Oncoematologia Azienda Ospedaliera Garibaldi

Catania, , Italy

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

Catanzaro, , Italy

Sez.Ematologia e Dip. scienze Biomediche Arcispedale S. Anna

Ferrara, , Italy

Azienda Ospedaliera di Firenze

Florence, , Italy

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

Foggia, , Italy

Clinica Ematologica - DiMI - Università degli Studi di Genova

Genova, , Italy

Clinica Ematologica - Università degli Studi

Genova, , Italy

A.O. Universitaria Policlinico Martina di Messina

Messina, , Italy

Azienda ospedaliera Ospedali Riuniti "Papardo Piemonte"

Messina, , Italy

Sez. di medicina Interna Oncologia ed Ematologia

Modena, , Italy

Universtià degli Studi di Napoli "Federico II" - Facoltà di medicina e chirurgia

Napoli, , Italy

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

Novara, , Italy

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

Orbassano, , Italy

Ospedali Riuniti "Villa Sofia-Cervello"

Palermo, , Italy

U.O. Ematologia Clinica - Azienda USL di Pescara

Pescara, , Italy

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

Piacenza, , Italy

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

Reggio Calabria, , Italy

Unità operativa complessa di Ematologia

Reggio Emilia, , Italy

A.O Umberto I

Roma, , Italy

Complesso Ospedaliero S. Giovanni Addolorata

Roma, , Italy

Ospedale S.Eugenio

Roma, , Italy

Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, , Italy

U.O. Ematologia, Azienda Ospedaliera Universitaria Senese

Siena, , Italy

Azienda ospedaliera S. Maria di Terni

Terni, , Italy

SCDO Ematologia 2 AOU S.Giovanni Battista

Torino, , Italy

Policlinico Universitario Udine

Udine, , Italy

Policlinico G. B. Rossi - Borgo Roma

Verona, , Italy

Ospedale San Bortolo

Vicenza, , Italy

Countries

Italy

References

Castagnetti F, Gugliotta G, Baccarani M, Breccia M, Specchia G, Levato L, Abruzzese E, Rossi G, Iurlo A, Martino B, Pregno P, Stagno F, Cuneo A, Bonifacio M, Gobbi M, Russo D, Gozzini A, Tiribelli M, de Vivo A, Alimena G, Cavo M, Martinelli G, Pane F, Saglio G, Rosti G; GIMEMA CML Working Party. Differences among young adults, adults and elderly chronic myeloid leukemia patients. Ann Oncol. 2015 Jan;26(1):185-192. doi: 10.1093/annonc/mdu490. Epub 2014 Oct 30.

Reference Type: DERIVED

PMID: 25361995 (View on PubMed)

Other Identifiers

GIMEMA-CML0408

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2008-004384-19

Identifier Type: -

Identifier Source: secondary_id

EU-20881

Identifier Type: -

Identifier Source: secondary_id

CML0408

Identifier Type: -

Identifier Source: org_study_id