E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
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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 assess the ability of POL6326 to mobilise CD (cluster of differentiation) 34+ cells in newly-diagnosed patients with multiple myeloma following intravenous (IV) infusion of POL6326 after pre treatment with three cycles of standard induction with a bortezomib or thalidomide based induction therapy, including adriamycin and/or dexamethasone, such as bortezomib + dexamethasone (PD), bortezomib + adriamycin + dexamethasone (PAD), thalidomide + dexamethasone (TD) or thalidomide + adriamycin + dexamethasone (TAD). |
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E.2.2 | Secondary objectives of the trial |
•To determine the safety and tolerability of POL6326 following 2-hour IV infusions in patients with multiple myeloma. •To determine th2-hour IV infusions e pharmacokinetic profile of POL6326 in plasma following 2-hour infusions in patients with multiple myeloma. •To determine efficacy in terms of haematopoietic reconstitution after high-dose melphalan following transplantation using stem cells mobilised by POL6326.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Have multiple myeloma in Stage II or III, according to the criteria of Durie and Salmon 2. Male or female between 18 and 70 years of age, inclusive. Male and females capable of reproduction must agree to use adequate contraceptive measures (e.g. condom, intrauterine device, oral contraceptive) until 3 months after termination of treatment. 3. Historic (i.e. before induction therapy) and/or current Measurable disease, defined by one of the following: • Serum M protein ≥1.0 g/dL by protein electrophoresis • Quantifiable immunoglobulin levels and/or urinary M protein excretion ≥200 mg/24 hours. 4. Have undergone 3 cycles of induction chemotherapy, with the last dose of IV chemotherapy given 3 to 8 weeks before receipt of POL6326. 5. Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2. 6. Life expectancy of >6 months. 7. Have given their written informed consent to participate in the study 8. Have not previously received G-CSF and not undergone haematopoietic stem cell transplantation.
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E.4 | Principal exclusion criteria |
1. Have non secretory myeloma and/or plasma cell leukaemia. 2. History of other malignancies during the past 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin, or cervical carcinoma, or localised prostate carcinoma. 3. Any other clinically significant medical conditions. 4. History of cardiac disease NHYA classification ≥3 5. Insufficient bone marrow, liver and renal function as assessed by the following clinical laboratory evaluations: • Haemoglobin <9.0 g/L • Absolute neutrophil count <1500/µL • Platelet count <50000/µL • Total bilirubin >1.5 x upper limit of normal (ULN) • Alanine aminotransferase (ALT) and alkaline phosphatase >2.5 x ULN • Amylase and lipase >1.5 x ULN • Serum creatinine >2.0 x ULN • Prothrombin time (PT) and activated partial thermoplastic time (APTT) >1.5 x ULN 6. Pregnant or lactating female patients. 7. Known history of HIV infection or chronic hepatitis B or C infection. 8. Receipt of immunotherapy, radiation therapy, or any investigational drug within 30 days of study drug administration. 9. Prior radiotherapy to more than 3 vertebrae. 10. Active serious bacterial or fungal infections; ≥grade 3 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. 11. Receipt of haematopoietic cytokines within 10 days of study drug administration.
Patients must be compliant with all inclusion and exclusion criteria to be eligible for inclusion.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is: • Percentage of patients achieving the minimal number of CD34+ cells (≥2 x 106/kg Body Weight:BW) collected during one to three cycles of apheresis which are considered necessary and safe to proceed with autotransplantation.
The secondary efficacy endpoints are: • The degree of CD34+ mobilisation in peripheral blood following 2 hour infusion of POL6326. Successful mobilisation is defined as ≥2 fold increase in CD34+ count or a count of at least 2-5 CD34+/µl following infusion of POL6326 and prior to apheresis compared to baseline (pre infusion). • Number of CD34+ cells collected during each cycle of apheresis. • The number of apheresis cycles and volume of apheresis required to obtain the minimal number of CD34+ cells necessary for autotransplantation (≥2 x 106/kg BW). • The number of tumour cells in apheresis product collected following the first dose of POL6326 compared with the number of tumour cells in product collected in the first apheresis cycle following CAD and G-CSF mobilisation. • Number of patients proceeding to autotransplantation of haematopoietic stem cells collected following treatment with POL6326. • Time to reach engraftment after high dose melphalan therapy. • Number of patients reaching engraftment. • Evaluation of response (International Uniform Response Criteria for Multiple Myeloma1-citeria) for multiple myeloma to assess clinical outcome following stem cell transplantation.
The safety endpoints will be : • Treatment emergent adverse events during Part 1 of the study and suspected unexpected treatment emergent serious adverse events during Part 2 of the study. • Evaluation of safety parameters (vital signs, body temperature, 12 lead electrocardiograph: ECG, physical examination, clinical laboratory evaluations).
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 | 0 |
E.8.9.1 | In the Member State concerned days | |
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 | 0 |