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

NCT00852566 | Completed Phase 2

• 1 other identifier: 2008-004106-13
• Study Type: interventional
• Target: 46
• Locations: 3 countries
• Sites: 7

Brief Summary

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.

Conditions

Chronic Myeloid Leukemia

Keywords

Chronic myeloid leukemia; tyrosine kinase inhibitor; stem cell; Philadelphia chromosome; dasatinib

Outcome Measures

Primary Outcomes (1)

• Ph-positive cells in stem cell compartments

  proportion of Ph-positive cells in stem cell compartments (CD34+CD38neg and CD34+CD38+)

  6 months

Secondary Outcomes (1)

• BCR-ABL RQ-PCR in blood

  up to 18 months (1, 3, 6, 12 and 18 months)

Study Arms (2)

Imatinib

ACTIVE COMPARATOR

Standard treatment Imatinib 400mg OD

Drug: Imatinib

dasatinib

EXPERIMENTAL

Dasatinib 100mg OD

Drug: Dasatinib

Interventions

Imatinib DRUG

Per oral imatinib 400mg once daily (continuous medication)

Also known as: Glivec

Imatinib

Dasatinib DRUG

Per oral dasatinib 100mg once daily (continuous medication)

Also known as: Sprycel

dasatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Norwegian University of Science and Technology: lead

Study Sites (7)

Helsinki University Central Hospital

Helsinki, 00029, Finland

Location

Bergen University Central Hospital

Bergen, Norway

Location

Rikshospitalet

Oslo, 0027, Norway

Location

St. Olavs Hospital

Trondheim, 7006, Norway

Location

Lund University Hospital

Lund, 22185, Sweden

Location

Karolinska University Hospital

Stockholm, 17176, Sweden

Location

Uppsala University Hospital

Uppsala, 75185, Sweden

Location

Related Publications (3)

• Hjorth-Hansen H, Stenke L, Soderlund S, Dreimane A, Ehrencrona H, Gedde-Dahl T, Gjertsen BT, Hoglund M, Koskenvesa P, Lotfi K, Majeed W, Markevarn B, Ohm L, Olsson-Stromberg U, Remes K, Suominen M, Simonsson B, Porkka K, Mustjoki S, Richter J; Nordic CML Study Group. Dasatinib induces fast and deep responses in newly diagnosed chronic myeloid leukaemia patients in chronic phase: clinical results from a randomised phase-2 study (NordCML006). Eur J Haematol. 2015 Mar;94(3):243-50. doi: 10.1111/ejh.12423. Epub 2014 Sep 13.

  PMID: 25082346 RESULT

• Christiansson L, Soderlund S, Mangsbo S, Hjorth-Hansen H, Hoglund M, Markevarn B, Richter J, Stenke L, Mustjoki S, Loskog A, Olsson-Stromberg U. The tyrosine kinase inhibitors imatinib and dasatinib reduce myeloid suppressor cells and release effector lymphocyte responses. Mol Cancer Ther. 2015 May;14(5):1181-91. doi: 10.1158/1535-7163.MCT-14-0849. Epub 2015 Mar 11.

  PMID: 25761894 DERIVED

• Mustjoki S, Richter J, Barbany G, Ehrencrona H, Fioretos T, Gedde-Dahl T, Gjertsen BT, Hovland R, Hernesniemi S, Josefsen D, Koskenvesa P, Dybedal I, Markevarn B, Olofsson T, Olsson-Stromberg U, Rapakko K, Thunberg S, Stenke L, Simonsson B, Porkka K, Hjorth-Hansen H; Nordic CML Study Group (NCMLSG). Impact of malignant stem cell burden on therapy outcome in newly diagnosed chronic myeloid leukemia patients. Leukemia. 2013 Jul;27(7):1520-6. doi: 10.1038/leu.2013.19. Epub 2013 Jan 18.

  PMID: 23328954 DERIVED

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome

Interventions

Imatinib Mesylate; Dasatinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Translocation, Genetic; Chromosome Aberrations

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Thiazoles; Sulfur Compounds; Azoles

Study Officials

• Satu Mustjoki, MD, PhD

  Helsinki University Central Hospital, helsinki, Finland

  PRINCIPAL INVESTIGATOR

• 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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2009
• First Posted: February 27, 2009
• Study Start: March 1, 2009
• Primary Completion: February 1, 2011
• Study Completion: December 1, 2015
• Last Updated: September 25, 2017

Record last verified: 2017-09

Locations

NO (3); SE (3); FI (1)