A phase II, multi-center, non-randomized, open-label study of TKI258 in patients with relapsed or refractory multiple myeloma, who are with or without t(4;14) translocation - N/A

• Conditions: Patients with relapsed or refractory multiple myeloma, who are with or without t(4; 14) translocation; MedDRA version: 13.1Level: PTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2009-012417-22-DE
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-02-17
• Last Update Posted: 27 January 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 80

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)
F.1.3.1 Number of subjects for this age range

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-versushost
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, but except nitrosourea, mitomycin-C, and anti-cancer
monoclonal antibody), less than 2 weeks prior to the start of 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 < 50% or lower limit of normal (whichever is higher) (ECHO) or
Multiple gated acquisition scanning (MUGA) < 45 % or lower limit of normal (which ever is higher)
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 antihypertensive
medication(s). Initiation or adjustment of antihypertensive medication(s) is allowed prior to study
entry.
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, who are biolo

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified