Exploratory Study of IMATINIB High Dose in Intermediate Risk Chronic Myeloid Leukemia in Chronic Phase

This study has been completed.
Sponsor:
Information provided by:
University of Bologna
ClinicalTrials.gov Identifier:
NCT00510926
First received: August 2, 2007
Last updated: NA
Last verified: August 2007
History: No changes posted
  Purpose

Results in CP are better in patients treated early after the onset of the disease with respect to late CP . To date, the early McR rate to imatinib is clearly higher in low and intermediate risk versus high risk (88 and 84% versus 65%). High dose of imatinib, as shown in phase I-III trials may offer the possibility to increase the response rate of patients belonging to this risk category.


Condition Intervention Phase
Myeloid Leukemia, Chronic, Chronic-Phase
Drug: Imatinib Mesilate (Glivec)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: CML/021 "A Phase II Exploratory Study of IMATINIB High Dose (800mg/gg) in the Treatment of Newly Diagnosed Intermediate Risk Chronic Myeloid Leukemia in Chronic Phase"

Resource links provided by NLM:


Further study details as provided by University of Bologna:

Primary Outcome Measures:
  • Rate of complete cytogenetic response at 12 months

Secondary Outcome Measures:
  • The rate of major cytogenetic response at 6 and 12 months.
  • The kinetic of cytogenetic response at 6 and 12 months
  • The duration of complete cytogenetic response.
  • The rate and duration of hematologic response.
  • The degree and the timing of molecular response (see section 13 and 14.5).
  • The time to accelerated and blast crisis and overall survival (see section 14.2)
  • The safety and tolerability of the treatment.

Estimated Enrollment: 80
Study Start Date: January 2004
Estimated Study Completion Date: November 2006
Detailed Description:

This is a phase II multicenter, open-label study designed to investigate the efficacy (hematological response, cytogenetic response and molecular response) and feasibility (tolerance, compliance and safety) of the tyrosine kinase inhibitor imatinib mesylate (formerly STI 571, GLIVECÔ, Novartis Pharma) at high dose (800 mg/daily) (serial number protocol ICSG/CML/021) in patients with Ph+ chronic myeloid leukemia (CML) in chronic phase (CP) previously untreated, at intermediate Sokal risk.

With aIFN, responses (HR and CgR) are significantly influenced by the disease phase and, in CP patients, by risk. aIFN induces rare and short lived HR and CgR (any degree) in late CP and particularly in accelerated and blastic phase.

Moreover, in CP patients Sokal's risk influences significantly the probability of obtaining a MCgR after aIfaIFN . As far as survival, after aIFN even in CCgR patients, the long term survival is signifcantly influenced by risk. The European investigators on Interferon in CML (EICML) collected informations on response and survival on 317 complete cytogenetic responders to IFN. The 10 years survival of the whole patients population was 75% but, after stratification by risk, a significant difference in 10 years survival rates was found in favour of low risk patients (89%) if compared with intermediate risk (70%) and high risk patients (54%) (low vs high risk p 0.0001; intermediate vs high p 0.003, log-rank test).

Long term survival data still lacks after imatinib. However, it has been already shown that the disease phase influences the efficacy of imatinib in CML: responses (HR and particularly CgR) are better in CP versus accelerated and blastic phase. Results in CP are better in patients treated early after the onset of the disease with respect to late CP . To date, the early McR rate to imatinib is clearly higher in low and intermediate risk versus high risk (88 and 84% versus 65%).

Two scoring systems are available for disease risk evaluation, Sokal and Euro. Sokal risk is based on chemotherapy treated patients and Euro risk is based on aIFN trated patients: it is not known to date if one or both of the scoring systems will apply to imatinib treated patients. Moreover, the Sokal system has been applied to stratify the patients by risk in all the large clinical trials of imatinib in CML in the last 3 years and consequently, Sokal score will be employed in the present trial.

Study objectives

Primary:

To determine the rate of complete cytogenetic response at 12 months in adult patients with previously untreated intermediate Sokal risk CML treated with imatinib 800 mg/daily

Secondary:

To determine:

  1. The rate of major cytogenetic response at 6 and 12 months.
  2. The kinetic of cytogenetic response at 6 and 12 months
  3. The duration of complete cytogenetic response.
  4. The rate and duration of hematologic response.
  5. The degree and the timing of molecular response
  6. The time to accelerated and blast crisis and overall survival
  7. The safety and tolerability of the treatment.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age >/=18 years
  • First chronic phase, less than 6 months of duration
  • Intermediate Sokal's risk
  • Ph positive
  • No previous treatment or hydroxiurea only.
  • Performance status (ECOG/WHO) < or = 2
  • Written informed consent

Exclusion Criteria:

  • Age <18
  • Low or high Sokal risk score.
  • More than 6 months from diagnosis.
  • Second chronic, accelerated or blastic phase
  • Scheduled allogeneic stem cell transplantation within 1 year from diagnosis.
  • Performance status (ECOG/WHO) > 2 (see Appendix 2)
  • Inability to provide written informed consent
  • Pregnancy
  • Formal refusal of any recommendation of a safe contraception
  • Alcohol or drug addiction
  • Altered hepatic or renal function as defined by AST/ALT or bilirubine > 3 times upper normal limits (UNL) and by creatinine ³ 20mg/L Any other disease or condition that by the advise of the responsible physician would make the treatment dangerous for the patient or would make the patient ineligible for the study, including physical, psychiatric, social and behavioural problems.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00510926

Locations
Italy
Policlinico S.Orsola-Malpighi, Istituto di Ematologia e Oncologia Medica "L. e A. Seràgnoli"
Bologna, Italy, 40138
Sponsors and Collaborators
University of Bologna
Investigators
Principal Investigator: Michele Baccarani, MD Policlinico S.Orsola-Malpighi - Istituto di Ematologia e Oncologia Medica "L. e A.Seràgnoli", Bologna
  More Information

No publications provided by University of Bologna

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

ClinicalTrials.gov Identifier: NCT00510926     History of Changes
Other Study ID Numbers: CML/021
Study First Received: August 2, 2007
Last Updated: August 2, 2007
Health Authority: Italy: The Italian Medicines Agency
Italy: Ethics Committee

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Chronic Disease
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Disease Attributes
Pathologic Processes
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 27, 2014