E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
A pilot study assessing how patients with AL amyloidosis respond to combination chemotherapy with velcade |
|
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 | 14.1 |
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 |
|
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 |
The REVEAL Trial aims to assess the efficacy, safety and tolerability of two bortezomib-based combination chemotherapy regimens:
VD (bortezomib [Velcade], and dexamethasone) and CVD (cyclophosphamide, bortezomib [Velcade] and dexamethasone)
in a randomized parallel phase II design in patients with AL amyloidosis who have Mayo stage II or III disease. |
|
E.2.2 | Secondary objectives of the trial |
Primary objectives:
1. Clonal response to VD and CVD
2. safety and tolerability of VD and CVD
The secondary research questions are to assess the following:
1. Amyloidotic organ response
2. Overall Survival
3. Relapse free survival
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1 - Aged 18 years or greater.
2 - Systemic AL amyloidosis who fulfil all the following criteria:
(i) Measurable clonal disease in the serum as defined by either a serum paraprotein of >7g/L or the abnormal component of the serum free light chain >75mg/L or dFLC >50 mg/L(only dFLC in case of renal failure),
(ii) Amyloid related organ dysfunction or organ syndrome,
(iii) Untreated Mayo Stage II or III patients
3- Capable of providing written, informed consent. |
|
E.4 | Principal exclusion criteria |
a. Overt symptomatic non-amyloid manifestations of multiple myeloma
b. Amyloidosis of unknown or non AL type
c. Localised AL amyloidosis (in which amyloid deposits are limited to a typical single organ, for example the bladder or larynx, in association with a clonal proliferative disorder within that organ)
d. Trivial or incidental AL amyloid deposits in the absence of a significant amyloid related organ syndrome (e.g., isolated carpal tunnel syndrome)
e. Allogeneic stem cell transplantation
f. Solid organ transplantation
g. Severe peripheral neuropathy or autonomic neuropathy causing significant functional impairment.
h. Thrombocytopenia (platelet count < 50x109/l)
i. Neutropenia (neutrophil count < 1x109/l)
j. Liver involvement by amyloid causing bilirubin >2 times or alkaline uthorized >4 times upper limit of normal
k. eGFR <20ml/min but not on dialysis (patients on dialysis are not excluded)
l. Significant ventricular arrhythmias
m. NYHA class IV heart failure
n. ECOG performance status >3
o. Estimated life expectancy of less than 3 months
p. Concurrent active malignancies, except surgically removed basal cell carcinoma of the skin or other in situ carcinomas
q. Pregnant, lactating or unwilling to use adequate contraception
r. Intolerance / sensitivity to any of the study drugs |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Clonal response of the underlying plasma cell dyscrasia to VD and to CVD.
2. Safety and toxicity of VD and CVD. |
|
E.5.2 | Secondary end point(s) |
1. Improvement in amyloidotic organ function
2. Overall Survival
3. Relapse free surviva |
|
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 | 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 | 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
| 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 | 19 |
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 | Information not present in EudraCT |
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
|
The end of trial from the regulatory point of view will be defined as the date of the last patient's last study visit. |
|
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 | 7 |
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 | 7 |