CML0408: Nilotinib and Imatinib Mesylate in Treating Patients With Early Chronic Phase Chronic Myelogenous Leukemia

Sponsor
Gruppo Italiano Malattie EMatologiche dell'Adulto (Other)
Overall Status
Completed
CT.gov ID
NCT00769327
Collaborator
(none)
129
37
68
3.5
0.1

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: imatinib mesylate
  • Drug: nilotinib
  • Genetic: cytogenetic analysis
  • Genetic: fluorescence in situ hybridization
  • Genetic: microarray analysis
  • Genetic: mutation analysis
  • Genetic: polymerase chain reaction
  • Genetic: polymorphism analysis
  • Other: laboratory biomarker analysis
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
129 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Front-line Treatment of Philadelphia Positive (Ph Pos), BCRABL Positive, Chronic Myeloid Leukemia (CML) With Two Tyrosine Kinase Inhibitors (TKI) (Nilotinib and Imotinib) A Phase II Exploratory Multicentric Centre.
Actual Study Start Date :
Feb 9, 2009
Actual Primary Completion Date :
Oct 1, 2014
Actual Study Completion Date :
Oct 10, 2014

Outcome Measures

Primary Outcome Measures

  1. Complete cytogenetic response rate [At 12 months from study entry]

Secondary Outcome Measures

  1. Complete cytogenetic response [At at 6 and 24 months from study entry]

  2. Major and complete molecular response rate [At at 6, 12 and 24 months from study entry]

  3. Development of BCR-ABL kinase domain mutations (number, timing, and type) [At at 24 months during and for 3 years after study treatment]

  4. Rate of failures and the time to failure [At 12, 24, and 60 months from study entry]

  5. Safety and tolerability [At 24 months from study entry]

  6. Frequency and type of adverse events (AE) and severe AE [At 24 months from study entry]

  7. Relationship between response, the gene expression profile, the biomarkers of leukemic cells, and plasma concentrations of nilotinib and imatinib mesylate [At 24 months from study entry]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 120 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Centro Oncologico Basilicata Rionero in Vulture Potenza Italy
2 Ospedale Civile Alessandria Alessandria Italy I-15100
3 Dipartimento Area Medica P.O. Ascoli Piceno Italy 63100
4 S.G. Moscati Hospital Avellino Italy 83100
5 Unità Operativa Ematologia 1 - Università degli Studi di Bari Bari Italy 70010
6 Ospedali Riuniti di Bergamo Bergamo Italy 24100
7 Ist.Ematologia e Oncologia Medica L.e A. Seragnoli Bologna Italy
8 ASL N.8 - Ospedale "A. Businco" - Struttura Complessa di Ematologia e CTMO Cagliari Italy
9 Ctc U.O Di Ematologia Con Trapianto Di Midollo Osseo - Catania Catania Italy
10 Unità di Oncoematologia Azienda Ospedaliera Garibaldi Catania Italy
11 Azienda Ospedaliera Pugliese Ciaccio - Presidio Ospedaliero A.Pugliese - Unità Operativa di Ematologia Catanzaro Italy
12 Sez.Ematologia e Dip. scienze Biomediche Arcispedale S. Anna Ferrara Italy 44100
13 Azienda Ospedaliera di Firenze Firenze Italy 50011
14 Struttura Complessa di Ematologia Ospedali Riuniti Foggia - Azienda Ospedaliero-Universitaria Foggia Italy
15 Clinica Ematologica - DiMI - Università degli Studi di Genova Genova Italy
16 Clinica Ematologica - Università degli Studi Genova Italy
17 A.O. Universitaria Policlinico Martina di Messina Messina Italy
18 Azienda ospedaliera Ospedali Riuniti "Papardo Piemonte" Messina Italy
19 Sez. di medicina Interna Oncologia ed Ematologia Modena Italy
20 Universtià degli Studi di Napoli "Federico II" - Facoltà di medicina e chirurgia Napoli Italy
21 S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro Novara Italy
22 Dip. di Scienze Cliniche e Biologiche - Ospedale S. Luigi Gonzaga Orbassano Italy
23 Ospedali Riuniti "Villa Sofia-Cervello" Palermo Italy
24 U.O. Ematologia Clinica - Azienda USL di Pescara Pescara Italy 65100
25 Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza Piacenza Italy
26 Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli" Reggio Calabria Italy
27 Unità operativa complessa di Ematologia Reggio Emilia Italy
28 A.O Umberto I Roma Italy
29 Complesso Ospedaliero S. Giovanni Addolorata Roma Italy
30 Ospedale S.Eugenio Roma Italy
31 Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza San Giovanni Rotondo Italy
32 U.O. Ematologia, Azienda Ospedaliera Universitaria Senese Siena Italy 53100
33 Azienda ospedaliera S. Maria di Terni Terni Italy
34 SCDO Ematologia 2 AOU S.Giovanni Battista Torino Italy
35 Policlinico Universitario Udine Udine Italy 33100
36 Policlinico G. B. Rossi - Borgo Roma Verona Italy 37134
37 Ospedale San Bortolo Vicenza Italy 36100

Sponsors and Collaborators

  • Gruppo Italiano Malattie EMatologiche dell'Adulto

Investigators

  • Principal Investigator: Michele Baccarani, MD, Gruppo Italiano Malattie EMatologiche dell'Adulto

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier:
NCT00769327
Other Study ID Numbers:
  • CML0408
  • GIMEMA-CML0408
  • EUDRACT-2008-004384-19
  • EU-20881
First Posted:
Oct 9, 2008
Last Update Posted:
Jan 4, 2022
Last Verified:
Jan 1, 2022

Study Results

No Results Posted as of Jan 4, 2022