Chronic myeloid leukemia MedDRA version: 21.1 Level: LLT Classification code 10009015 Term: Chronic myeloid leukemia System Organ Class: 100000004864 MedDRA version: 21.0 Level: LLT Classification code 10009016 Term: Chronic myeloid leukemia in remission System Organ Class: 100000004864 MedDRA version: 21.0 Level: LLT Classification code 10009700 Term: CML System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Tasigna
Product Name: Nilotinib
Product Code: AMN107
Pharmaceutical Form: Capsule
Trade Name: Galvus
Product Name: Vildaglipitin
Pharmaceutical Form: Tablet
Sponsors
Albert Schweitzer Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients =18 years of age. 2. At diagnosis chronic myeloid leukemia in chronic phase. 3. Previous relapse during attempt at TFR (Treatment Free Remission) 4. Documented regain of deep molecular remission at the level of at least MR4.0, defined as a measurable BCR-ABL level =0.01% IS or an undetectable BCR-ABL with a minimal total control gene copy number of ABL1 ?10 000 or GUSB ?24 000 in two replicates. A sample showing MR4.0 or better needs to have been taken within 31 days of study inclusion. 5. Continuous treatment with any TKI for a minimum of 12 months prior to entering the study 6. No other current or planned anti-leukemia therapy. 7. ECOG Performance status 0,1, or 2. 8. Adequate organ function as defined by: a) Total bilirubin 30 ml/min. f) Mg++, K+ =LLN. 9. Life expectancy of more than 12 months in the absence of any intervention 10. Written informed consent to participate in the study Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Prior accelerated phase or blast crisis. 2. Patient has received another investigational agent within last 6 months. 3. Prior stem cell transplantation. 4. History of occlusive cardiovascular disease, including peripheral occlusive arterial disease, cerebrovascular disease and coronary artery disease. 5. Other clinically significant uncontrolled heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension) 6. Increased risk of cardiac arrhythmia, defined as: a) Inability to monitor the QT/QTc interval on ECG. b) Long QT syndrome or a known family history of long QT syndrome. c) Clinically significant resting brachycardia (450 msec on baseline ECG (using the QTcF formula). If QTcF >450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc. e) History of or presence of clinically significant ventricular or atrial tachyarrhythmias 6. Known atypical BCR-ABL transcript not quantifiable by standard RQ-PCR 7. History of active malignancy during the past 2 years with the exception of basal carcinoma of the skin or carcinoma in situ of cervix uteri or breast. 8. Acute liver disease or cirrhosis. 9. Previous or active acute or chronic pancreatic disease. 10. Another severe and/or life-threatening medical disease. 11. History of significant congenital or acquired bleeding disorder unrelated to cancer. 12. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug. 13. Patients actively receiving therapy with strong CYP3A4 inhibitors where the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. 14. Patients who are currently receiving treatment with any medication that has 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. 15. Patients who are: a) pregnant. b) breast feeding. c) of childbearing potential without a negative pregnancy test prior to baseline. d) male or female of childbearing potential unwilling to use contraceptive precautions throughout the trial (post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential). 16. Interruption of TKI therapy for a cumulative period in excess of 21 days in the preceding 3 months. 17. Known intolerance to nilotinib 18. Known intolerance to vildagliptin 19. History of non-compliance, or other inability to grant informed consent. 20. Past or present history of alcohol abuse, use of illicit drugs, or severe psychiatric disorders, including depression. 21. Autoimmune hepatitis or a history of autoimmune disease. 22. Pre-existing thyroid disease unless it can be controlled with conventional treatment. 23. Epilepsy and/or compromised central nervous system (CNS) function. 24. HCV/HIV patients. 25. Poorly controlled diabetes mellitus(i.e. HbA1c >9.0) or clinically relevant diabetic complications such as neuropathy, retinopathy, nephropathy, coronary or peripheral vascular disease.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Achieving succesful Treatment Free Remission (TFR) in patients with Chronic Myeloid Leukemia (CML) who have previously failed a TFR attempt;Secondary Objective: Not applicable;Primary end point(s): For phase 1 part of the study: Occurrence of drug-related adverse events causing dose limiting toxicity for vildagliptin when added to nilotinib treatment in CML patients For phase 2 part of the study: Reduction of Ph+CD34+CD38-CD26+ cell frequency in bone marrow in CML patients before and after addition of vildagliptin to nilotinib in CML patients ;Timepoint(s) of evaluation of this end point: Phase 1: 4 week monitoring interval Phase 2: At baseline, after 3 and 6 months of vildagliptin-co-treatment At 3,6,12 and 18 monts after nilotinib (TKI) discontinuation | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): For phase 1 part of the study: AE rate for the combination of vildagliptin and nilotinib treatment in CML patients For phase 2 part of the study: 1. The percentage of patients showing a reduction of at least one log of BCR-ABL levels in bone marrow or peripheral blood by nilotinib-vildagliptin co-treatment 2. the percentage of patients with undetectable Ph+CD34+CD38-CD26+ cells in the bone marrow after TKI discontinuation and after vildagliptin discontinuation 3. the percentage of patients in treatment-free remission 6 months after TKI discontinuation while still treated with vildagliptin 4. the percentage of patients in treatment-free remission 12 months after TKI discontinuation (6 months after vildagliptin discontinuation) 5. the incidence of infectious adverse effects during nilotinib/vildagliptin co-treatment ;Timepoint(s) of evaluation of this end point: Phase 1: 4 week monitoring interval Phase 2: At baseline, after 3 and 6 months of vildagliptin-co-treatment At 3,6,12 and 18 monts after nilotinib (TKI) discontinuation | — |
Countries
Belgium, Netherlands
Contacts
Public ContactPrinicpal Investigator
Albert Schweitzer Hospital
Outcome results
None listed