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Comparing Imatinib Standard Dose With Imatinib High Dose Induction in Pretreated Chronic Myeloid Leukemia (CML) Patients in Chronic Phase

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2005 by Central European Leukemia Study Group.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Central European Leukemia Study Group
ClinicalTrials.gov Identifier:
NCT00327262
First received: May 16, 2006
Last updated: June 16, 2006
Last verified: September 2005

May 16, 2006
June 16, 2006
January 2004
Not Provided
To determine the efficacy regarding major cytogenetic response within 12 months after randomization
To determine efficacy regarding major cytogenetic response within 12 months after randomization.
Complete list of historical versions of study NCT00327262 on ClinicalTrials.gov Archive Site
  • To determine the major cytogenetic response after 3 months versus 6-12 months after randomization
  • To determine the efficacy of the molecular response within 12 and 24 months after randomization
  • To determine the time to molecular progression within 24 months
  • To determine the dynamics of the molecular response within 3 and 6 months after randomization expressed as the slope decreases in BCR-ABL-transcripts
  • To determine tolerability
  • To determine major cytogenetic response after 3 months vs. 6-12 months after randomization.
  • To determine efficacy of the molecular response within 12 and 24 months after randomization.
  • To determine time to molecular progression within 24 months.
  • To determine dynamics of the molecular response within 3 and 6 months after randomization. expressed as the slope of decrease of bcr/abl-transcripts.
  • To determine tolerability
Not Provided
Not Provided
 
Comparing Imatinib Standard Dose With Imatinib High Dose Induction in Pretreated Chronic Myeloid Leukemia (CML) Patients in Chronic Phase
Multicenter, Phase III Study Comparing Imatinib (STI571, Glivec®) Standard Dose (400 Mg/Day) With Imatinib High Dose Induction (800 Mg/Day) Followed by Standard Dose Maintenance (400 Mg/Day) in Pretreated CML Patients in Chronic Phase

This study will investigate the efficacy and tolerability of a short (6 months) high dose therapy followed by a standard dose compared to a continuous treatment with a standard dose of imatinib (Glivec®) in pretreated Philadelphia chromosome- positive (Ph+)/BCR-ABL+ CML patients in chronic phase.

Patients with CML not achieving or losing a major cytogenetic response on whatever palliative treatment for CML, are at high risk to progress to accelerated phase and blast crisis. A new promising treatment with Imatinib (Glivec®), a tyrosine-kinase inhibitor, has been introduced recently. High rates of hematologic and cytogenetic responses can be achieved with Imatinib (Glivec®) at > = 300 mg/day in chronic phase CML patients that are refractory, resistant or intolerant to interferon-alpha. However, about 10 – 20% of these high risk patients will lose their response to Imatinib (Glivec®) within 1-2 years. Therefore, improvement of the treatment is warranted.

Since cytogenetic response rate is correlated to survival and the resistance to Imatinib (Glivec®) might be caused by mutations in the receptor, a more rapid decrease could lead to longer survival and/or less resistance development. In the initial 6 months of treatment, monotherapy with Imatinib (Glivec®) with a dose of 800 mg/day (high dose) should be more effective in the reduction of a high leukemic tumor burden, thereby allowing the residual normal progenitor and stem cells to expand. In addition, high dose Imatinib (Glivec®) should further improve the induction of a molecular response, as determined by quantitative reverse transcription polymerase chain reaction (RT-PCR), reducing the risk of relapse from residual malignant BCR-ABL positive cells.

This study will investigate the efficacy and tolerability of a short (6 months) high dose therapy followed by a standard dose compared to a continuous treatment with a standard dose of Imatinib (Glivec®).

In addition, the dynamics of the molecular and cytogenetic response will be investigated. Finally, the study will investigate the effect of this induction-maintenance concept on time-to-progression (TTP).

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Chronic Myeloid Leukemia
Drug: Imatinib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
240
December 2008
Not Provided

Inclusion Criteria:

  1. Patients > 18 years of age
  2. BCR-ABL positive CML patients in chronic phase, confirmed by karyotype (Ph+) or RT-PCR.
  3. Patients pretreated with any drug that is known to control the disease of CML in chronic phase except imatinib (Glivec®).
  4. Patients without a major cytogenetic response at study entry (> 35% Ph+ metaphases in bone marrow cytogenetic analysis performed < 3 months before study entry).
  5. Patients either intolerant to interferon-alpha (non-hematologic toxicity grade 3-4 for more than 2 weeks) or having received pretreatment for CML at least 12 months before study entry.
  6. World Health Organization (WHO) status 0-2
  7. Adequate end organ function, defined as the following:

    • total bilirubin < 1.5 x upper limit of normal (ULN)
    • SGOT and SGPT < 2.5 x ULN
    • creatinine < 1.5 x ULN
    • absolute neutrophil count (ANC) > 1.5 x 10 ^ 9/L
    • platelets > 100 x 10 ^ 9/L
  8. Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug.
  9. Written voluntary informed consent.

Exclusion Criteria:

  1. Patients eligible for allogeneic bone marrow transplantation.
  2. Patients in accelerated phase or blast crisis.
  3. Known tuberculosis or other uncontrolled infection.
  4. Other primary tumor of a different histological origin than the study indication (unless the relapse-free interval is > 5 years, and with the exception of cervical carcinoma in situ [CIS], basal cell epithelioma, or squamous cell carcinoma of the skin).
  5. Major surgery within the last 14 days.
  6. Known to be HIV positive.
  7. Unstable medical disorder (except for indication) that excludes the patient in the opinion of the investigator.
  8. Patient has received any other investigational agents within 28 days of first day of study drug dosing.
  9. Patients with a WHO performance status score > 3
  10. Patients with Grade III/IV cardiac problems as defined by the New York Heart Association criteria (i.e., congestive heart failure, myocardial infarction within 6 months of study).
  11. Female patients who are pregnant or breast-feeding.
  12. Refusal by female patients of childbearing age to use a safe contraceptive.
  13. Patients with known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
  14. Patients with any significant history of non-compliance to medical regimens or an inability to grant reliable informed consent.
Both
18 Years and older
No
Contact: Guenther Gastl, MD ++43 512 504 24003 guenther.gastl@uibk.ac.at
Austria
 
NCT00327262
CSTI571AAT06
Not Provided
Not Provided
Central European Leukemia Study Group
Not Provided
Study Chair: Guenther Gastl, MD Medical University Innsbruck
Central European Leukemia Study Group
September 2005

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP