Patients with relapsed or refractory multiple myeloma, who are with or without t(4
Conditions
Interventions
Product Code: TKI258
Pharmaceutical Form: Capsule, hard
Current Sponsor code: TKI258
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Cytopathologically or histologically confirmed diagnosis of multiple myeloma previously requiring systemic treatment. 2. Evidence of relapsed or refractory disease as documented from the prior treatment history (Refractory myeloma is defined as disease that is non-responsive while on salvage therapy, or progresses within 60 days of last therapy. Relapsed myeloma is defined as previously treated myeloma which after a period of being off-therapy requires the initiation of salvage therapy. Detailed definitions provided in the PTS-1). 3. Have received at least 2 prior treatment regimens for multiple myeloma including chemotherapy, autologous transplantation, immunotherapy, or other investigational agents. Pre-planned induction followed by transplant and maintenance should be considered as one regimen. 4. Presence of measurable disease as defined by at least one of the following; • Serum M-protein = 1g/dL (measurable disease) • Urine M-protein = 200mg/24 hours by protein electrophoresis (measurable disease) 5. Age = 18 years. 6. WHO (World Health Organization) performance status of = 2. 7. Must have the following baseline laboratory values; • Absolute neutrophil count = 1000/mm3 (or = 750/mm3 if neutropenia is clinically related to progressive myeloma with bone marrow infiltration) [SI units, 1.0x109/L,and 0.75x109/L, respectively) • Platelet count = 75,000/mm3 (or = 50,000/mm3 if thrombocytopenia is clinically indicated to progressive myeloma with bone marrow infiltration) [SI units, 75x109/L,and 50x109/L, respectively) (transfusion support allowed) • Hemoglobin (Hgb) = 8 g/dl (transfusion support allowed) • AST and ALT = 3.0 x ULN • Serum bilirubin = 1.5 x ULN • Electrolyte levels = LLN (i.e., potassium, magnesium, phosphorus), correction with supplements allowed • Serum creatinine = 2.0 x ULN (or 24-hour creatinine clearance = 50 ml/min) 8. Willing and able to undergo bone marrow aspirations and bone marrow biopsies as per the study center’s practice and protocol requirements. 9. Life expectancy of =12 weeks. 10. Must provide written informed consent to participate in this 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients with non-secretory, or oligosecretory, multiple myeloma. 2. Patients with symptomatic amyloidosis, or with plasma cell leukemia. 3. Patients who have received allogeneic stem cell transplantation and who show evidence of active graft-versus-host disease that requires immunosuppressive therapy. 4. Patients with history of another malignancy within the last three years prior to study entry, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix. 5. Patients who have received the last administration of anticancer therapy (for example chemotherapy, immunotherapy, hormonal therapy, and targeted therapy), less than 2 weeks prior to the start of this study drug, and who have not recovered from the side effects of such therapy. Patients who have received the last administration of nitrosourea, mitomycin-C = 6 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy. 6. Patients who received the last administration of an anti-cancer monoclonal antibody = 6 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy. 7. Patients who have received any other investigational agents = 4 weeks prior to starting study drug or who have not recovered from the side effects of such therapy. 8. Patients who have received wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) = 4 weeks or limited field radiation for palliation = 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy. 9. Patients who have undergone a major surgery = 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy. 10. Impaired cardiac function or clinically significant cardiac diseases, including any of the following: • History or presence of serious uncontrolled cardiac arrhythmias • Clinically significant resting bradycardia • LVEF assessed by 2-D echocardiogram (ECHO) or Multiple gated acquisition scanning (MUGA) < 45 % 11. Any of the following within 6 months prior to study entry: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE). 12. Uncontrolled hypertension defined by SBP =160 mmHg and/or DBP =100 mmHg, with or without anti-hypertensive medication. 13. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of TKI258 (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). 14. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory). 15. Patients who are currently receiving anticoagulation treatment with therapeutic doses of warfarin. 16. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol. 17. Pregnant or breast-feeding women. 18. Male and female patients of child-bearing potential not employing an effective method of birth control. Barrier contraceptives must be used throughout the trial and one month after the end of treatment. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study. Women of c
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the extended overall response rates of orally administered TKI258, at 500 mg/day, on a five days on and two days off dosing schedule, in groups of patients with relapsed or refractory multiple myeloma who are • with t(4;14) translocation (Group 1). • without t(4;14) translocation (Group 2).;Secondary Objective: • To assess the safety profile of TKI258 dosing schedule, in the two groups. • To assess the overall response rates as per IMWG in the two groups. • To evaluate PFS in the two groups. • To evaluate plasma exposure of TKI258 in all patients who receive single agent TKI258.;Primary end point(s): Extended overall response rate (Extended ORR) as defined by the rate of patients with best overall response of CR, VGPR (very good partial response) or PR (IMWG ORR), plus patients with best overall response MR as defined according to IMWG. Serum or urine M-protein levels will be measured at the end of each cycle. Confirmation of certain responses may require plasma cell count, evaluation of soft tissue plasmacytoma, or lytic bone lesions. | — |
Countries
France, Germany, Netherlands, Spain
Outcome results
None listed