Chronic myeloid leukemia
Conditions
Interventions
None listed
Sponsors
Vrije Universiteit Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Molecular diagnosis of CP CML of =100 x 109/L platelets (>=100,000/mm3); e) No evidence of extramedullary disease except hepatosplenomegaly; AND f) No prior diagnosis of AP or BP-CML. • Philadelphia chromosome status will be identified at screening. Both Ph+ and Ph- patients may be included. 2. Adequate hepatic and renal function defined as: • AST/ALT =18 years. 6. Negative serum pregnancy test within 2 weeks of the first dose of study drug if the patient is a woman of childbearing potential. A woman of childbearing potential is defined as a woman who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives. Patients and patient's partners of childbearing potential (physically able to have children) and who are sexually active, must agree to use birth control consistently and correctly during the study and for at least 28 days after they have stopped taking the study drug. 7. Ability to provide written informed consent prior to any study related screening procedures being performed.
Exclusion criteria
Exclusion criteria: 1. Any prior medical treatment for CML, including TKIs, with the exception of hydroxyurea and/or anagrelide treatment. 2. Any past or current CNS involvement, including leptomeningeal leukemia. 3. Hypersensitivity to the active substance or to any of the following excipients: microcrystalline cellulose (E460), croscarmellose sodium (E468), poloxamer 188, povidone (E1201), magnesium stearate (E470b), polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, Talc (E553b), iron oxide red (E172). 4. Extramedullary disease only. 5. Major surgery or radiotherapy within 14 days of randomization. 6. Concomitant use of or need for medications known to prolong the QT interval. 7. History of clinically significant or uncontrolled cardiac disease 8. Known seropositivity to human immunodeficiency virus (HIV), current acute or chronic hepatitis B (hepatitis B surface-antigen positive), hepatitis C or evidence of decompensated liver disease or cirrhosis. 9. Recent or ongoing clinically significant GI disorder, e.g. Crohn*s Disease, Ulcerative Colitis, or prior total or partial gastrectomy. 10. History of another malignancy within 5 years with the exception of basal cell carcinoma or cervical carcinoma in situ or stage 1 or 2 cancer that is considered adequately treated and currently in complete remission for at least l2 months. 11. Uncontrolled hypomagnesemia or uncorrected hypokalemia due to potential effects on the QT interval. 12. Current, or recent (within 6 months), participation in other clinical trials. 13. Women who are pregnant, planning to become pregnant during the study or are breastfeeding a child, or men who are planning to father a child during the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is to define whether bosutinib and /or imatinib therapy induces numerical or functional changes in the immune effector cells as assessed by flow cytometry and functional assays of peripheral blood samples. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary aims of the study are: (a) to correlate the immunological effects of therapy with achievement of major molecular response at 12, 18 and 24 months and with achievement of MR4.0 and MR4.5 at 12,18 and 24 months. (b) To correlate the immune cell profile at diagnosis with early molecular response (BCR-ABL % IS) at 3 months. (c) To find biological markers which can predict the response to TKI therapy, and possibly also which patients are able to discontinue the therapy without disease relapse. (d) To assess the leukemia stem cell (LSC) burden at diagnosis and after 3 months of therapy by flow cytometry and correlate that to therapy response and hematological toxicity. (e) To identify novel CML LSC markers by a comprehensive antibody screen and RNA sequencing. This includes assessment of leukotriene and DNA repair signaling. (f) To analyse phosphoprotein signalling both in CD34+ and mononuclear cell fractions and study the effect of bosutinib and imatinib on it and correlate the phosphoprotein profile to clinical responses. | — |
Countries
Netherlands
Outcome results
None listed