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

August 2, 2007 updated by: University of Bologna

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"

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment

80

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Bologna, Italy, 40138
        • Policlinico S.Orsola-Malpighi, Istituto di Ematologia e Oncologia Medica "L. e A. Seràgnoli"

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Rate of complete cytogenetic response at 12 months

Secondary Outcome Measures

Outcome Measure
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Bologna

Investigators

  • Principal Investigator: Michele Baccarani, MD, Policlinico S.Orsola-Malpighi - Istituto di Ematologia e Oncologia Medica "L. e A.Seràgnoli", Bologna

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2004

Study Completion

November 1, 2006

Study Registration Dates

First Submitted

August 2, 2007

First Submitted That Met QC Criteria

August 2, 2007

First Posted (Estimate)

August 3, 2007

Study Record Updates

Last Update Posted (Estimate)

August 3, 2007

Last Update Submitted That Met QC Criteria

August 2, 2007

Last Verified

August 1, 2007

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CML/021

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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