Advanced hematological malignancies MedDRA version: 2.3 Classification code 10048683
Conditions
Interventions
Product Name: LBH589
Product Code: LBH589
Pharmaceutical Form: Capsule, hard
Current Sponsor code: LBH589
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5 -
Produ
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Dose escalation phase for both arms •Patients with a cytopathologically confirmed diagnosis of AML, MDS (RAEB), ALL, CLL, CML (blast, accelerated, chronic), multiple myeloma, and Non-Hodgkin’s Lymphoma (including mantle cell and follicular lymphoma; excluding CTCL and Burkett’s lymphoma) who are either relapsed after or refractory to standard therapy, and are considered inappropriate candidates for standard therapy •Patients with a cytopathologically confirmed diagnosis of AML or MDS (RAEB) who are previously untreated but due to age, poor prognosis, or concurrent medical conditions are considered inappropriate candidates for standard induction therapy, or those who refuse standard induction therapy • Patients with a confirmed diagnosis of myelofibrosis with myeloid metaplasia. Splenectomized patients must have a clinical indication for therapy (i.e., they must require therapy) • Dose expansion phase for both arms: • Group A: AML – Cytopathologically confirmed diagnosis of AML or MDS (RAEB) who are either relapsed after or refractory to standard therapy, and are considered inappropriate candidates for standard therapy and de novo AML in elderly patients with high risk factors • Group B: CML (BP, AP, CP) – Patients with a cytopathologically confirmed diagnosis of CML are either relapsed after or refractory to no more than 3 prior therapies (one of which must have been imatinib) or, are intolerant of these therapies. • Group C: MM – Patients with relapsed or relapsed/refractory multiple myeloma who have received at least one (but no more than three) prior therapies, and have demonstrated disease progression on the last therapy. • Group D: Patients with a cytopathologically confirmed diagnosis of relapsed/refractory ALL, CMML, CML – atypical (BCR-ABL negative), CLL, PLL (T- and B-cell), HL, and NHL (excluding CTCL and Burkitt’s lymphoma), and myelofibrosis with myeloid metaplasia (For more information see protocol) 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: • Impaired cardiac function or clinically significant cardiac disease • Patients who are currently receiving treatment with medications that have a relative risk of prolonging the QT interval or inducing Torsades de Pointes (For more information see protocol) • No concurrent brain metastases or leukemic infiltration of the CSF. However, patients with a prior history of brain metastases from another indication or a prior history of leukemic infiltration of the CSF, who have demonstrated resolution of the CNS involvement and no evidence of CNS involvement at baseline, are eligible. • Presence of unstable atrial fibrillation (ventricular response>100bpm). Patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiad exclusion criteria. • Patients who are currently receiving treatment with any of the inhibitors of CYP3A4 listed in Table 3-7, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug. • Women of child bearing potential (WCBP) who are pregnant or breast feeding. WCBP, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test <72 hours prior to starting study treatment. In addition, all sexually active WCBP and male patients must agree to use adequate contraceptive methods (oral injectable or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermacide; or vasectomized partner) throughout the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. MTD and DLT of single agent LBH589B when administered orally, once-a-day on MWF, every week, in adult patients with advanced hematologic malignancies which has progressed despite standard therapy or for which no standard therapy exists (Arm 1) 2. MTD and DLT of single agent LBH589B when administered orally, once-a-day on MWF, every other week, in adult patients with advanced hematologic malignancies which has progressed despite standard therapy or for which no standard therapy exists (Arm 2) 3. To characterize the pharmacokinetic profile of LBH589, and its potential metabolite(s), after single and repeated doses of LBH589 ;Secondary Objective: Safety and tolerability, Pharmacokinetic profile, biomarkers and exploratory biomarker development, preliminary evidence of anti-leukemic or anti-tumor activity, response rate in disease-specific groups. (For more information see protocol) ;Primary end point(s): MTD and DLT of single agent LBH589B in every week and every other week dosing schedules. (For more information see protocol) | — |
Countries
Germany
Outcome results
None listed