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Randomized Study Comparing the Effect of Dasatinib and Imatinib on Malignant Stem Cells in Chronic Myeloid Leukemia (NordCML006)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Norwegian University of Science and Technology
ClinicalTrials.gov Identifier:
NCT00852566
First received: February 26, 2009
Last updated: November 18, 2011
Last verified: November 2011
History of Changes
  Purpose

A randomized multi-center study comparing the effect of dasatinib and imatinib on malignant stem cells in newly diagnosed chronic phase chronic myeloid leukemia (CML) patients. The research hypothesis is that treatment with dasatinib 100 mg daily (QD) results in greater and more rapid depletion of the Philadelphia (Ph) -positive stem cell pool within 6 months of therapy than imatinib 400 mg QD in newly diagnosed CML patients. The study duration is 18 months and approximately 40 patients will be recruited to the study.


Condition Intervention Phase
Chronic Myeloid Leukemia
 Drug: Imatinib
Drug: Dasatinib
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Randomized, Multicenter Phase II Trial Comparing the Depletion of Malignant Stem Cells With Dasatinib vs. Imatinib in Patients With Newly Diagnosed Chronic Phase Chronic Myeloid

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Norwegian University of Science and Technology:

Primary Outcome Measures:
  • Ph-positive cells in stem cell compartments [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    proportion of Ph-positive cells in stem cell compartments (CD34+CD38neg and CD34+CD38+)


Secondary Outcome Measures:
  • BCR-ABL RQ-PCR in blood [ Time Frame: up to 18 months (1, 3, 6, 12 and 18 months) ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: March 2009
Estimated Study Completion Date: December 2015
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Imatinib
Standard treatment Imatinib 400mg OD
 Drug: Imatinib
Per oral imatinib 400mg once daily (continuous medication)
Other Name: Glivec
Experimental: dasatinib
Dasatinib 100mg OD
 Drug: Dasatinib
Per oral dasatinib 100mg once daily (continuous medication)
Other Name: Sprycel

Detailed Description:

An Open-Label, Randomized, Multicenter Phase II Trial Comparing the depletion of malignant stem cells with Dasatinib vs. Imatinib in Patients with Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia

Estimated Number of Study Centers and Countries/Regions: Appr. 12 sites in 5 Nordic countries. Stem cell analyses will be performed in 4 Nordic centers (Helsinki, Lund, Oslo and Stockholm).

Study Phase: II

Research Hypothesis: Treatment with dasatinib 100 mg daily (QD) results in greater and more rapid depletion of the Philadelphia (Ph) -positive stem cell pool within 6 months of therapy than imatinib 400 mg QD in newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML) patients.

Primary Objective: To compare the number of Ph-positive cells in the stem cell compartment in newly diagnosed CP CML patients treated with dasatinib 100 mg QD vs. imatinib 400 mg QD.

Study Design: open-label randomized Phase II trial in newly diagnosed CML patients in CP. Patients will be randomized to receive dasatinib at a starting dose of 100 mg QD or imatinib at a starting dose of 400 mg QD.

Duration of Study: The study will be open for enrollment until the planned number of 40 patients is randomized. All patients will be treated and/or followed for up to 18 months. Based on the amendment 1 (Oct 2011), the follow-up of the patients will continue additional 4 years until 31.12.2015.

Number of Patients per Group: Approximately 40 patients will be randomized, 20 patients to dasatinib and 20 to imatinib. Additional patients will be recruited in case insufficient amount of representative samples have been obtained from first 40 patients.

Study Population: Patients 18 years or older with a newly diagnosed CP CML, not previously treated with any systemic treatments for CML

Study Assessments and Endpoints:

All stem cell assays are based on the preselection of CD34+ cells from large volume of bone marrow (BM) aspirates using paramagnetic beads. The CD34+ fraction will be further subdivided based on the expression of CD38 marker (positive vs. negative) using a sorting flow cytometer.

The primary endpoint is a comparison of proportion of Ph-positive cells in stem cell compartments (CD34+CD38neg and CD34+CD38+) at 6 months between the study arms.

Secondary endpoints are comparisons between treatment arms for: (1) the number of Ph-positive cells in all stem cell compartments at 1 and 3 months, (2) BCR-ABL RQ-PCR in blood at 1, 3, 6, 12 and 18 months, and (3) rate of CCyR within 3, 6, 12 and 18 months.

  Eligibility

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

Inclusion Criteria:

  • Patients are able to provide written informed consent

  • Patients must have CML in CP which is defined by the presence of all of the following criteria:

    • < 15% blasts in peripheral blood (PB) and BM.
    • < 30% blasts plus promyelocytes in PB and BM.
    • < 20% basophils in the PB.
    • ≥ 100 x 109/L platelets.
    • No evidence of extramedullary leukemia apart from hepatosplenomegaly
    • Ph+ or variants must be demonstrated by BM cytogenetics, FISH or PCR.
    • Previously untreated CML in CP, with the exception of hydroxyurea or anagrelide
  • Patients must be enrolled in this study within 90 days after the date of first being diagnosed with CML
  • ECOG Performance Status (PS) Score 0 - 1 (see Appendix 2)
  • Adequate hepatic function defined as: total bilirubin ≤ 2.0 times the institutional upper limit of normal (ULN) in absence of Gilbert type unconjugated hyperbilirubinemia; alanine aminotransferase (ALAT≤ 2.5 times the institutional ULN.
  • Adequate renal function defined as serum creatinine ≤ 2 times the institutional ULN.
  • Men and women, ages 18 years and older.
  • Adequate BM aspiration sample before the start of study treatment (i.e sample is sufficient for stem cell analysis)
  • Potentially fertile women must use an adequate method of contraception to avoid pregnancy throughout the study.
  • Potentially fertile women must have a negative serum or urine pregnancy test

Exclusion Criteria:

  • Fertile women who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study
  • Women who are pregnant or breastfeeding.
  • Men with fertile sexual partners who can or will not use an acceptable contraception method for the entire study
  • A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy.
  • Known pleural effusion at baseline.
  • Uncontrolled or significant cardiovascular disease
  • History of significant bleeding disorder unrelated to CML, including:
  • Prior chemotherapy for peripheral stem cell mobilization.
  • Inadequate BM aspiration sample due to marrow fibrosis or other reasons
  • Prior or concurrent malignancy
  • Severe psychiatric illness, imprisonment or mental impairment inflicting on ability to give informed consent
  • Abuse of alcohol, prescribed or illicit drugs
  • Evidence of digestive dysfunction that would prevent administration of study therapy by mouth.

  • Prohibited Treatments and/or Therapies

    • Any prior treatment with interferon
    • Any prior treatment with dasatinib
    • Any prior treatment with imatinib
    • Any other prior systemic treatments, with anti-CML activity [except for anagrelide, or hydroxyurea (HU)].
  • Patients currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes as described in Appendix 3.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00852566

Locations
Finland
Helsinki University Central Hospital
Helsinki, Finland, 00029
Norway
Bergen University Central Hospital
Bergen, Norway
Rikshospitalet
Oslo, Norway, 0027
St. Olavs Hospital
Trondheim, Norway, 7006
Sweden
Lund University Hospital
Lund, Sweden, 22185
Karolinska University Hospital
Stockholm, Sweden, 17176
Uppsala University Hospital
Uppsala, Sweden, 75185
Sponsors and Collaborators
Norwegian University of Science and Technology
Investigators
Principal Investigator: Satu Mustjoki, MD, PhD Helsinki University Central Hospital, helsinki, Finland
Study Chair: Henrik Hjorth-Hansen, MD, PhD St Olavs Hospital, Trondheim, Norway
Study Chair: Ole Weiss-Bjerrum, MD, PhD Rigshospitalet, Denmark
Study Chair: Ingunn Dybedal, MD, PhD Rikshospitalet, Oslo, Norway
Study Chair: Tobias Gedde-Dahl, MD, PhD Rikshospitalet, Oslo, Norway
Study Chair: Kimmo Porkka, MD, PhD Helsinki University Central Hospital, Helsinki, Finland
Study Chair: Johan Richter, MD, PhD University of Lund, Lund, Sweden
Study Chair: Bengt Simonsson, MD, PhD University Hospital, Uppsala, Sweden
Study Chair: Leif Stenke, MD, PhD Karolinska Institutet
  More Information

No publications provided

Responsible Party: Norwegian University of Science and Technology
ClinicalTrials.gov Identifier: NCT00852566     History of Changes
Other Study ID Numbers: 2008-004106-13
Study First Received: February 26, 2009
Last Updated: November 18, 2011
Health Authority: Finland: Finnish Medicines Agency

Keywords provided by Norwegian University of Science and Technology:
Chronic myeloid leukemia
tyrosine kinase inhibitor
stem cell
Philadelphia chromosome
dasatinib

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
Dasatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 23, 2013