E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10002022 |
E.1.2 | Term | Amyloidosis |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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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 determine the efficacy of bortezomib plus dexamethasone followed by HDM and auto-SCT in patients with newly diagnosed AL amyloidosis who are 18-70 years inclusive. |
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E.2.2 | Secondary objectives of the trial |
To asses the safety of bortezomib plus dexamethasone in the induction regimen followed by HDM and autologous SCT in patients with newly diagnosed AL amyloidosis who are 18-70 years inclusive |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Biopsy proven, systemic, untreated AL amyloidosis requiring systemic chemotherapy,
• Age 18 -70 years inclusive at the time of signing the informed consent form,
• Measurable plasma cell dyscrasia, defined as a detectable M-protein with serum electrophoresis and/or level of involved FLC> 50 mg/L,
• Life expectancy > 3 months,
• WHO performance status 0-2,
• NYHA 1-2,
• Negative pregnancy test at inclusion for women of childbearing potential,
• Written informed consent.
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E.4 | Principal exclusion criteria |
• Multiple Myeloma stage II and III (Durie and Salmon),
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form,
• Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule,
• Previous treatment for plasma cell dyscrasia
• Pregnant or breast feeding females.
• Presence of other active malignancy or a history of active malignancy during the past 5 years, with the exception of nonmelanoma skin cancer, stage 0 cervical carcinoma, or treated early-stage prostate cancer provided that prostate-specific antigen is within normal limits,
• Hypersensitivity to boron or mannitol,
• Uncontrolled infection,
• Symptomatic othostatic hypotension defined as a decrease in systolic blood pressure on standing of >20mmHg combined with symptoms like dizziness, cerebral and/or cardial ischemia,
• Symptomatic effusions, defined as pleural effusion or ascites needing drainage therapy,
•NT pro BNP level > 5000 pg/ml and Troponin T> 0.06 microgram/l (not high senstitivity assay) or NT proBNP level > 5000 pg/ml and Troponin I > 2 times ULN
• Positive for HIV or infectious hepatitis, B or C,
• Bilirubin > 2x upper limit of normal,
• Creatinin clearance < 30 ml/min (after rehydration),
• Absolute neutrophil count < 1.0 × 109/L,
• NCI CTCAE grade peripheral sensory neuropathy > grade 2,
• NCI CTCAE grade peripheral sensory neuropathy > grade 1 in the presence of neuropathic pain,
•NCI CTCAE grade peripheral motor neuropathy > grade 2
• Concurrent diagnosis of B-cel NHL or B-CLL,
• Previous organ transplantation.
• Unwilling or unable to use adeaquate contraception
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E.5 End points |
E.5.1 | Primary end point(s) |
• Hematological CR rate 6 months after auto-SCT.
Patients are considered a success if they received HDM and auto-SCT and are in complete hematological response at 6 months, all other patients are considered a failure. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
About 10 months after inclusion of last patient |
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E.5.2 | Secondary end point(s) |
• OS
• PFS
• Hematological response rate after induction therapy
• Response rate, hematological and organ
• Time to response, hematological and organ
• Duration of hematological and organ response
• Time to next AL amyloidosis therapy
• Safety (type, frequency, and severity of adverse events (AE) and relationship of AE to study drug
•Exploratory assessment of multiparameter flow cytometry quantification of bone marrow plasma cells and change in amyloid deposition in abdominal fat aspiration samples
•Evaluation of prognostic factors for survival included in the hematological and organ response criteria
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
About 10 months after inclusion of last patient. May be repeated at later analysis |
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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 | 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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 9 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 9 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |