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

NCT00769327 | Completed Phase 2

• 4 other identifiers: CML0408GIMEMA-CML0408EUDRACT-2008-004384-19EU-20881
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 37

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.

Conditions

Leukemia

Keywords

chronic myelogenous leukemia, BCR-ABL1 positive; chronic phase chronic myelogenous leukemia

Outcome Measures

Primary Outcomes (1)

• Complete cytogenetic response rate

  At 12 months from study entry

Secondary Outcomes (7)

• Complete cytogenetic response

  At at 6 and 24 months from study entry

• Major and complete molecular response rate

  At at 6, 12 and 24 months from study entry

• Development of BCR-ABL kinase domain mutations (number, timing, and type)

  At at 24 months during and for 3 years after study treatment

• Rate of failures and the time to failure

  At 12, 24, and 60 months from study entry

• Safety and tolerability

  At 24 months from study entry

Interventions

imatinib mesylate DRUG

nilotinib DRUG

cytogenetic analysis GENETIC

fluorescence in situ hybridization GENETIC

microarray analysis GENETIC

mutation analysis GENETIC

polymerase chain reaction GENETIC

polymorphism analysis GENETIC

laboratory biomarker analysis OTHER

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Gruppo Italiano Malattie EMatologiche dell'Adulto: lead

Study Sites (37)

Centro Oncologico Basilicata

Rionero in Vulture, Potenza, Italy

Location

Ospedale Civile Alessandria

Alessandria, I-15100, Italy

Location

Dipartimento Area Medica P.O.

Ascoli Piceno, 63100, Italy

Location

S.G. Moscati Hospital

Avellino, 83100, Italy

Location

Unità Operativa Ematologia 1 - Università degli Studi di Bari

Bari, 70010, Italy

Location

Ospedali Riuniti di Bergamo

Bergamo, 24100, Italy

Location

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

Bologna, Italy

Location

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

Cagliari, Italy

Location

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

Catania, Italy

Location

Unità di Oncoematologia Azienda Ospedaliera Garibaldi

Catania, Italy

Location

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

Catanzaro, Italy

Location

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

Ferrara, 44100, Italy

Location

Azienda Ospedaliera di Firenze

Florence, 50011, 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

Clinica Ematologica - Università degli Studi

Genova, Italy

Location

A.O. Universitaria Policlinico Martina di Messina

Messina, Italy

Location

Azienda ospedaliera Ospedali Riuniti "Papardo Piemonte"

Messina, Italy

Location

Sez. di medicina Interna Oncologia ed Ematologia

Modena, Italy

Location

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

Napoli, Italy

Location

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

Novara, Italy

Location

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

Orbassano, Italy

Location

Ospedali Riuniti "Villa Sofia-Cervello"

Palermo, Italy

Location

U.O. Ematologia Clinica - Azienda USL di Pescara

Pescara, 65100, Italy

Location

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

Piacenza, Italy

Location

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

Reggio Calabria, Italy

Location

Unità operativa complessa di Ematologia

Reggio Emilia, Italy

Location

A.O Umberto I

Roma, Italy

Location

Complesso Ospedaliero S. Giovanni Addolorata

Roma, Italy

Location

Ospedale S.Eugenio

Roma, Italy

Location

Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Italy

Location

U.O. Ematologia, Azienda Ospedaliera Universitaria Senese

Siena, 53100, Italy

Location

Azienda ospedaliera S. Maria di Terni

Terni, Italy

Location

SCDO Ematologia 2 AOU S.Giovanni Battista

Torino, Italy

Location

Policlinico Universitario Udine

Udine, 33100, Italy

Location

Policlinico G. B. Rossi - Borgo Roma

Verona, 37134, Italy

Location

Ospedale San Bortolo

Vicenza, 36100, Italy

Location

Related Publications (1)

• 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.

  PMID: 25361995 DERIVED

MeSH Terms

Conditions

Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase

Interventions

Imatinib Mesylate; nilotinib; Cytogenetic Analysis; In Situ Hybridization, Fluorescence; Microarray Analysis; Polymerase Chain Reaction; Amplified Fragment Length Polymorphism Analysis

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow 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; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; In Situ Hybridization; Staining and Labeling; Histocytological Preparation Techniques; Histological Techniques; Nucleic Acid Hybridization; Microchip Analytical Procedures; Nucleic Acid Amplification Techniques; DNA Fingerprinting

Study Officials

• Michele Baccarani, MD

  Gruppo Italiano Malattie EMatologiche dell'Adulto

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 8, 2008
• First Posted: October 9, 2008
• Study Start: February 9, 2009
• Primary Completion: October 1, 2014
• Study Completion: October 10, 2014
• Last Updated: January 4, 2022

Record last verified: 2022-01

Locations

IT (37)