Chronic myeloid leukemia
Conditions
Interventions
Trade Name: SPRYCEL (Dasatinib)
Product Name: Sprycel
Pharmaceutical Form: Tablet
Trade Name: PegIntron
Product Name: PegIntron
Pharmaceutical Form: Lyophilisate and solvent for suspension for injec
Sponsors
Norwegian University of Science and Technology
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria: 1. Age =18- 70 years of age 2. Diagnosis of chronic myeloid leukemia in chronic phase (CML-CP) associated with BCR-ABL1 quantifiable by RQ-PCR (IS) 3. No other current or planned anti-leukemia therapies excluding hydroxyurea treatment for up to two months. 4. ECOG Performance status 0,1, or 2 5. Adequate organ function as defined by: Total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: Exclusion criteria: 1. Prior accelerated phase or blast crisis 2. Uncontrolled or significant cardiovascular disease, including any of the following: a. A myocardial infarction within 6 months b. Uncontrolled angina within 3 months c. Congestive heart failure within 3 months d. Diagnosed or suspected congenital long QT syndrome e. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointe) f. Prolonged QTcF interval > 450 msec on pre-entry ECG 3. Atypical BCR-ABL1 transcript not quantifiable by RQ-PCR. 4. Another primary malignant disease, which requires systemic treatment (chemotherapy or radiation) 5. Severe and/or life-threatening medical disease including acute liver disease 6. History of significant congenital or acquired bleeding disorder unrelated to cancer 7. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dasatinib 8. Patients actively receiving therapy with strong CYP3A4 inhibitors and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug 9. Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug 10. Female patients who are: pregnant, breast feeding or potentially fertile without a negative pregnancy test prior to baseline or unwilling to use contraception on trial 11. History of non-compliance, abuse of alcohol, illicit drugs, severe psychiatric disorders or other inability to grant informed consent. 12. Hypersensitivity to any interferon preparation; 13. Autoimmune hepatitis or a history of autoimmune disease; 14. Pre-existing thyroid disease unless it can be controlled with conventional treatment; 15. Epilepsy and/or compromised central nervous system (CNS) function; 16. HCV/HIV patients 17. Depression requiring treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Observe toxicity of drug combination See protocol Observe effect measured as response by molecular assesment of BCR-ABL transcript. fraction in So called major molecular rfemission (i.e 3 log below debut levels) ;Secondary Objective: Observe toxicity of drug combination See protocol Observe fraction of patients who achieve a very good response (So called major molecular remission, which is less than a thousandth of the disease burden at diagnosis;Primary end point(s): Primary endpoint: Safety endpoint in run-in phase (first 15 patients): Study stops if four out of the first five, six of the first 10 or 8 of the first 15patients experience grade IV hematological toxicity, grade III non-hematological toxicity or grade II serosal effusions during first 6 months of treatment. Data will be evaluated by an independent safety committee. Whole study efficacy endpoint: Rate of MMR after 12 months. ;Timepoint(s) of evaluation of this end point: 6 months for safety 12 months for efficacy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoint (s) • Rate of CCgR after 3, 6, 12 and 18 months • Rate of MMR after 3, 6, 15, 18, and 24 months • Rate of MR4.0 and MR4.5 after 3, 6, 12, 15, 18, and 24 months • Rate of grade 2 non-hematological toxicity that poses a clinical problem (duration more than one month in spite of symptomatic treatment) • Rate of grade 3-4 hematological toxicity • Overall survival • Rate of patients who complete 3, 6 and 12 months of PegIFN treatment • QoL at 0, 3, 6, 12 and 18 months • Progression to advanced disease phase. • Comparison of safety and efficacy variables with historical cohorts from Nord CML006 and NordCML002 • Biomarkers of response, failure and toxicity. A) Fraction of leukemic cells in the stem cell (Ph+ CD34+CD38- cells) and progenitor cell (Ph+ CD34+CD38+) compartment at debut and 4 weeks of dasatinib treatment. B) Lymphocyte subpopulations at 0, 3 and 6 months by flow cytometry assay: Enumeration of CD4+ and CD8+ T-cells, NK-cells, NKT-cells, B-cells and regulatory T-cells. Correlation of these subpopulations to response. C) Functional assays of lymphocytes: Cytotoxicity of NK-cells. IFN-? production by T cells after stimulation. Granzyme B staining for evaluating the cytotoxic potential of T-cells. Functional assays will be performed both from pre- and post-drug samples. D) Clonality: TCR ?d rearrangements by PCR E) Plasma cytokine array: Luminex multiplex system F) Proteomics A simplified follow-up of treatment response by real-time quantitative reverse transcriptase PCR (RQ-PCR), treatment type, progression to advanced phase and survival will be performed yearly until end of year 5. ;Timepoint(s) of evaluation of this end point: See above | — |
Countries
Denmark, Finland, Norway, Sweden
Contacts
Public ContactHenrik Hjorth-Hansen
NTNU
Outcome results
None listed