E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Waldenstrom’s Macroglobulinemia or Multiple Myeloma |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine whether further study of single-agent enzastaurin is warranted in patients with previously treated WM or MM, based on RR. |
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E.2.2 | Secondary objectives of the trial |
to estimate the RR in patients with previously treated WM and in patients with previously treated MM • to estimate the TTP in patients with either WM or MM treated with enzastaurin • to assess the safety of enzastaurin in WM and MM • to explore the impact of adding dexamethasone to enzastaurin in WM and MM patients with PD. • to assess exploratory biomarkers relevant to enzastaurin and disease state, and assess their relationship with clinical outcome.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients are eligible to be included in the study only if they meet all of the following criteria: [1] At least 18 years of age. [2] Patients must have WM or MM previously treated with at least 1 and no more than 5 prior therapies. [3] Treatment with prior autologous transplant is permitted. If a transplant is used as consolidation following chemotherapy, without intervening disease progression, it will be considered 1 line of treatment with the preceding chemotherapy. [4a] Patients with MM must have a monoclonal protein in the serum of ≥1 g/dL or monoclonal light chain in the urine protein electrophoresis of ≥ 200 mg/ 24 hours, or measurable plasmacytoma. [4b] Patients with WM must have an immunoglobulin M (IgM) paraprotein with a minimum IgM level of ≥ 2 times the upper limit of normal, have detectable lymphoplasmacytic (LPL) cells in the bone marrow, and be symptomatic for WM. [5] ECOG Performance Status (PS) of 0, 1, or 2. See Protocol Attachment S042.5. [6] The following laboratory values obtained prior to registration: • Absolute neutrophil count (ANC) ≥1000/ µL • Platelet (PLT) count ≥75,000/ µL • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (if total is elevated check direct and, if normal, patient is eligible) • Aspartate transaminase (AST) ≤ 3 x ULN • Creatinine ≤1.5 x ULN • Hemoglobin (Hgb) ≥8.0 g/dL. [7] Expected survival of >12 weeks. [8] The ability to provide informed consent. [9] Male and female patients with reproductive potential must use an approved contraceptive method, if appropriate (for example, intrauterine device [IUD], birth control pills, or barrier device) during and for 3 months after discontinuation of study treatment. Women with childbearing potential must have a negative serum pregnancy test ≤ 3 days prior to study enrollment
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E.4 | Principal exclusion criteria |
Patients will be excluded from the study if they meet any of the following criteria: [10] Prior allogeneic hematopoietic stem cell transplant. [11] Are unable to discontinue use of non-EIAEDs, for example carbamazepine, phenobarbital, and phenytoin (refer to Section 5.6). Patients on anti-coagulant therapy should be monitored (see Section 5.6.2). Ongoing treatment with therapeutic doses of Coumadin is prohibited. However, prophylactic, low dose (≤ 2mg daily) Coumadin for DVT is allowed. In such cases, PT/INR should be closely monitored. [12] Have ECG abnormalities including baseline 12-lead ECG with QTc interval of >450 msec in males or >470 msec in females, or QRS duration of >100 msec. Patients who have a congenital long-QT-syndrome in their own or family medical history should be excluded at the investigator’s discretion. [13] Have an uncontrolled infection. [14] Have prior treatment with BCNU ≤ 6 weeks, alkylating agent ≤ 4 weeks, or other cytotoxic chemotherapy agents ≤ 4 weeks prior to registration in this trial. Have prior treatment with biologic therapy ≤ 12 weeks or corticosteroids ≤ 2 weeks prior to registration in this trial. However, treatment with ≤ 10 mg of prednisone as a chronic therapy is allowed. [15] Have radiation therapy ≤ 2 weeks prior to treatment in this trial. [16] Are pregnant or breast-feeding. [17] Are being treated with concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational. [18] Are known to be HIV positive. [19] Were previously treated with enzastaurin. [20] Patients who are unable to swallow tablets. [21] Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. [22] Concurrent malignancy that could complicate interpretation of response or safety evaluation. Non-melanoma skin cancer and carcinoma in situ of the cervix are not exclusions.
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E.5 End points |
E.5.1 | Primary end point(s) |
To determine whether further study of single-agent enzastaurin is warranted in patients with previously treated WM or MM, based on RR. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |