E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Multiple Myeloma Harbouring the t (4;14) translocation with or without FGFR3 Expression |
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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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the anti-tumor activity of PHA-739358 in patients with Multiple Myeloma (MM) harbouring the t (4;14) translocation. |
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E.2.2 | Secondary objectives of the trial |
- To define the safety profile of PHA-739358 in MM patients, - To investigate the inhibition of Aurora kinase and FGFR3 signalling in bone marrow plasma cells.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult (age ≥ 18 and ≤ 75 years) patients.
2. Confirmed diagnosis of active multiple myeloma that has relapsed or is refractory to at least two previous lines of treatments, including bortezomib and lenalidomide. At least 4 weeks should be elapsed between the end of the last therapy and the entry in the trial.
3. Patients with t (4;14) translocation.
4. Current measurable disease defined by at least one of the following two measurements: · Serum M-protein ≥ 1 g/dl · Urine M-protein ≥ 200 mg/24 h.
5. Prior radiotherapy is allowed provided that no more than 25% of bone marrow reserve has been irradiated and a minimum of 4 weeks have elapsed between the end of prior radiotherapy and the entry into the trial or less if one single lesion had to be irradiated for pain control.
6. ECOG performance status 0-1.
7. Life expectancy of at least 3 months.
8. Resolution of all acute toxic effects (excluding alopecia) of any prior surgery, radiotherapy, radio-surgery or chemotherapy to NCI CTC (Version 3.0) Grade ≤ 1 (exception: stable, grade 2 neuropathy is permitted).
9. Baseline laboratory values fulfilling the following requirements: Absolute Neutrophils Count (ANC) ≥ 1,500/mm3 (≥ 1.5 x 1000000000/L) Platelets ≥ 75,000/mm3 (≥ 75 x 1000000000/L) Hemoglobin ≥ 8.0 g/dL Serum Creatinine ≤ 2.0 mg/dL ( ≤ 177 micromol/L) Direct Serum Bilirubin ≤ 1.5 x ULN Liver Transaminases (AST/ALT) ≤ 2.5 x ULN; ≤ 5 x ULN if liver involvement is present.
10. Signed and dated informed consent indicating that the patient is aware of the neoplastic nature of his/her disease and has been informed of the procedures to be followed, the experimental nature of the therapy, potential benefits, side effects, discomforts, risks, and alternative treatments.
11. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study indications or procedures.
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E.4 | Principal exclusion criteria |
1. Patients with non-detectable M-component (non-secretory myeloma).
2. Current enrollment in another therapeutic clinical trial.
3. Use of other investigational drugs (drugs not marketed for any indication) within 30 days prior to treatment.
4. Other prior malignancy, except for adequately treated basal or squamous cell skin cancer or superficial bladder cancer, ductal carcinoma in situ of the breast, or any other cancer from which the patient has been disease-free for 5 years or greater or that poses no immediate clinical threat to the patient.
5. Prior treatment with radiopharmaceuticals (e.g., Strontium-89, Samarium-153) within 8 weeks prior to enrollment.
6. Major surgery, within 4 weeks or not fully recovered prior to Day 1.
7. Pregnancy or breast feeding. Male and female patients sexually active not using an effective form of barrier contraception during the study and in the following 90 days after discontinuation of study treatment.
8. Uncontrolled hypertension with blood pressure exceeding 160/100 mmHg (Stage 2 hypertension according to the JNC 7/ NIH USA 2003 guideline).
9. Any of the following in the past 6 months: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis.
10. Cardiac dysrhythmias Grade ≥ 2 according to NCI CTCAE version 3.0.
11. Known active infections, including HIV positive.
12. History of allergic reactions to a similar structural compound, biological agent, or formulation.
13. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Response rate according to the International Myeloma Working Group uniform response criteria for multiple myeloma. |
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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 | 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 | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | No |
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.8.6 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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See protocol Section 9.2.2. |
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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 | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 10 |