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
  Purpose

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.


Condition Intervention Phase
Chronic Myeloid Leukemia
Drug: Imatinib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Central European Leukemia Study Group:

Primary Outcome Measures:
  • To determine the efficacy regarding major cytogenetic response within 12 months after randomization

Secondary Outcome Measures:
  • 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

Estimated Enrollment: 240
Study Start Date: January 2004
Estimated Study Completion Date: December 2008
Detailed Description:

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).

  Eligibility

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

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00327262

Contacts
Contact: Guenther Gastl, MD ++43 512 504 24003 guenther.gastl@uibk.ac.at

Locations
Austria
Medical University Innsbruck Recruiting
Innsbruck, Tyrol, Austria, 6020
Contact: Guenther Gastl, MD         
Contact: Dominic Fong, MD         
Principal Investigator: Guenther Gastl, MD         
Sponsors and Collaborators
Central European Leukemia Study Group
Investigators
Study Chair: Guenther Gastl, MD Medical University Innsbruck
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00327262     History of Changes
Other Study ID Numbers: CSTI571AAT06
Study First Received: May 16, 2006
Last Updated: June 16, 2006
Health Authority: Austria: Federal Ministry for Health and Women

Keywords provided by Central European Leukemia Study Group:
chronic myeloid leukemia
Ph+
bcr/abl+
imatinib

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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 July 22, 2014