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 | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
What is the 2-year progression-free survival (PFS) for patients who, having achieved CR/VGPR following PAD therapy, do not receive any further treatment until clinical indication of relapse? This question is addressed separately for patients who are minimal residual disease positive (MRD+), and those who are MRD negative (MRD-), at end of induction chemotherapy. |
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E.2.2 | Secondary objectives of the trial |
a. What is the overall response rate (CR/VGPR and PR) to PAD therapy in previously untreated patients with multiple myeloma? b. What percentage of patients become MRD negative as determined by multi-parameter flow (MPF) following PAD therapy? c. What percentage of patients proceeding to ASCT become MRD- at 100 days post-ASCT? d. What is the PFS of patients proceeding to ASCT? e. Does the level of activation of the Nfkappa-B pathway influence response rate and PFS in patients receiving PAD induction therapy for untreated MM? |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
i. Previously untreated patients with symptomatic myeloma ii. Patients suitable for high dose therapy and ASCT iii. ≥ 18 years of age iv. Performance score (PS) of 0-3 (ECOG) v. Measurable disease as defined by one of the following: a. Secretory myeloma: Monoclonal protein in the serum or monoclonal light chain in the urine (Bence Jones protein ≥200mg/24hours), or serum free light chain (SFLC, involved light chain ≥100mg/L provided the FLC ratio is abnormal) b. Non-secretory myeloma: ≥30% plasma cells in the marrow (aspirate and/or biopsy) and at least one plasmacytoma ≥2 cm as determined by clinical examination or applicable radiographs (i.e., MRI or CT scan) vi. Adequate full blood count within 14 days before registration: a. Platelet count ≥75x109/L b. Absolute neutrophil count (ANC) ≥1x109/L vii. Adequate renal function within 14 days before registration: a. Creatinine clearance >30ml/min viii. Adequate hepatobiliary function within 14 days before registration: a. Total bilirubin <2 x upper limit of normal (ULN) b. ALT/AST <2.5 x ULN ix. Adequate pulmonary function: a. No evidence of a history of infiltrative pulmonary disease. If a history, then KCO/DLCO (Carbon Monoxide diffusion in the lung) ≥50% and/or no requirement for supplementary continuous O2 x. Adequate cardiac function: a. Left ventricular ejection fraction (LVEF) ≥40% by Echocardiogram and ECG. xi. If female and of childbearing potential (WCBP), must have a negative pregnancy test (either serum or urine HCG) xii. Able to give informed consent |
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E.4 | Principal exclusion criteria |
i. Grade 2 peripheral neuropathy or neuropathic pain as defined by NCI Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) ii. Pregnant or breast-feeding iii. Unwilling to use adequate contraception during the study and for 6 months after the end of the study treatment if female of childbearing potential(WCBP), or male whose partner is WCBP iv. Known history of allergy contributable to compounds containing boron or mannitol v. Any medical or psychiatric condition which, in the opinion of the investigator, contraindicates the patient’s participation in this study |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival (PFS) in patients assigned to no further treatment until clinical indication of relapse. This will be determined for MRD+ and MRD- patients separately. PFS is defined as the time from date of PBSCH to date of the first progression/relapse or date of death from all causes whichever occurs first. |
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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 | Yes |
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 | 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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
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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The trial will close after the last patient has had their final study visit (i.e 24 months after Peripheral Blood Stem Cell Harvest/Autologous Stem Cell Transplant). Trial patients will then be in standard long term follow up. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |