Nilotinib and Imatinib Mesylate in Treating Patients With Early Chronic Phase Chronic Myelogenous Leukemia (CML0408)
This study is ongoing, but not recruiting participants.
Sponsor:
Gruppo Italiano Malattie EMatologiche dell'Adulto
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier:
NCT00769327
First received: October 8, 2008
Last updated: August 21, 2012
Last verified: August 2012
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Purpose
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 | Intervention | Phase |
|---|---|---|
|
Leukemia |
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 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: 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. |
Resource links provided by NLM:
Further study details as provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:
Primary Outcome Measures:
- Complete cytogenetic response rate [ Time Frame: At 12 months from study entry ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Complete cytogenetic response [ Time Frame: At at 6 and 24 months from study entry ] [ Designated as safety issue: No ]
- Major and complete molecular response rate [ Time Frame: At at 6, 12 and 24 months from study entry ] [ Designated as safety issue: No ]
- Development of BCR-ABL kinase domain mutations (number, timing, and type) [ Time Frame: At at 24 months during and for 3 years after study treatment ] [ Designated as safety issue: No ]
- Rate of failures and the time to failure [ Time Frame: At 12, 24, and 60 months from study entry ] [ Designated as safety issue: No ]
- Safety and tolerability [ Time Frame: At 24 months from study entry ] [ Designated as safety issue: Yes ]
- Frequency and type of adverse events (AE) and severe AE [ Time Frame: At 24 months from study entry ] [ Designated as safety issue: Yes ]
- Relationship between response, the gene expression profile, the biomarkers of leukemic cells, and plasma concentrations of nilotinib and imatinib mesylate [ Time Frame: At 24 months from study entry ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 114 |
| Study Start Date: | February 2009 |
| Estimated Study Completion Date: | August 2014 |
| Estimated Primary Completion Date: | August 2014 (Final data collection date for primary outcome measure) |
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00769327
Locations
| Italy | |
| Centro Oncologico Basilicata | |
| Rionero in Vulture, Potenza, Italy | |
| Ospedale Civile Alessandria | |
| Alessandria, Italy, I-15100 | |
| Dipartimento Area Medica P.O. | |
| Ascoli Piceno, Italy, 63100 | |
| S.G. Moscati Hospital | |
| Avellino, Italy, 83100 | |
| Unità Operativa Ematologia 1 - Università degli Studi di Bari | |
| Bari, Italy, 70010 | |
| Ospedali Riuniti di Bergamo | |
| Bergamo, Italy, 24100 | |
| 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 | |
| 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, 44100 | |
| Azienda Ospedaliera di Firenze | |
| Firenze, Italy, 50011 | |
| Struttura Complessa di Ematologia Ospedali Riuniti Foggia - Azienda Ospedaliero-Universitaria | |
| Foggia, Italy | |
| Clinica Ematologica - Università degli Studi | |
| Genova, Italy | |
| Clinica Ematologica - DiMI - Università degli Studi di Genova | |
| Genova, Italy | |
| Azienda ospedaliera Ospedali Riuniti "Papardo Piemonte" | |
| Messina, Italy | |
| A.O. Universitaria Policlinico Martina di Messina | |
| 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, 65100 | |
| 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 | |
| Complesso Ospedaliero S. Giovanni Addolorata | |
| Roma, Italy | |
| A.O Umberto I | |
| Roma, Italy | |
| Ospedale S.Eugenio | |
| Roma, Italy | |
| Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza | |
| S. G. Rotondo, Italy | |
| U.O. Ematologia, Azienda Ospedaliera Universitaria Senese | |
| Siena, Italy, 53100 | |
| Azienda ospedaliera S. Maria di Terni | |
| Terni, Italy | |
| SCDO Ematologia 2 AOU S.Giovanni Battista | |
| Torino, Italy | |
| Policlinico Universitario Udine | |
| Udine, Italy, 33100 | |
| Policlinico G. B. Rossi - Borgo Roma | |
| Verona, Italy, 37134 | |
| 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 |
More Information
Additional Information:
No publications provided
| Responsible Party: | Gruppo Italiano Malattie EMatologiche dell'Adulto |
| ClinicalTrials.gov Identifier: | NCT00769327 History of Changes |
| Other Study ID Numbers: | CML0408, GIMEMA-CML0408, EUDRACT-2008-004384-19, EU-20881 |
| Study First Received: | October 8, 2008 |
| Last Updated: | August 21, 2012 |
| Health Authority: | Italy: Ethics Committee |
Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:
|
chronic myelogenous leukemia, BCR-ABL1 positive chronic phase chronic myelogenous leukemia |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid, Chronic-Phase Neoplasms by Histologic Type Neoplasms Myeloproliferative Disorders Bone Marrow Diseases |
Hematologic Diseases Imatinib Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 16, 2013