E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Aplastic anemia and single-lineage bone marrow failure |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10002965 |
E.1.2 | Term | Aplasia pure red cell |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047350 |
E.1.2 | Term | Very few granulocyte precursors |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10002967 |
E.1.2 | Term | Aplastic anaemia |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10001507 |
E.1.2 | Term | Agranulocytosis |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic 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 |
To investigate safety and efficacy of the proposed treatment. |
|
E.2.2 | Secondary objectives of the trial |
1. Incidence of adverse effects after treatment with Campath 1H and CsA.
2. Long-term safety of Campath 1H treatment.
3. Time to achieve a complete hematological response.
4. Proportion of patients maintaining the hematological response free of any treatment.
5. Incidence of relapse in responding patients.
6. Incidence of severe infections.
7. Requirement of intravenous antibiotic and antifungal therapy.
8. Requirement of red cell and platelet transfusion.
9. Incidence of CMV reactivation.
10. Kinetic of immune reconstitution.
11. Incidence of patients developing a paroxysmal nocturnal hemoglobinuria (PNH) clone (lymphoid or myeloid).
12. Incidence of clonal evolution (i.e. karyotypic abnormalities, secondary myelodysplasia/leukemia). |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
ALTRI SOTTOSTUDI: Ricostituzione immunologica
|
|
E.3 | Principal inclusion criteria |
a. Diagnosis of severe or very severe aplastic anemia,22 defined by:
 At least two of the following:
Absolute neutrophil counts <0.5 x 109/L (severe) or <0.2 x 109/L (very severe)
Platelet counts <20 x 109/L
Reticulocyte counts <20 x 109/L
 Hypocellular bone marrow (<30% cellularity), without evidences of fibrosis or malignant cells
Or
Diagnosis of single lineage acquired marrow failure, such as:
 Pure Red Cell Aplasia (PRCA
 Agranucytosis
 Amegakaryocytic thrombocytopenia
b. Failure of first line therapy with ATG+CsA, or lack of eligibily for ATG-based studies. Failure is defined as follows:
- lack of hematological response
- need of chronic IS treatment to sustain response
- relapse
c. Age ≥18 years
d. Written informed consent |
|
E.4 | Principal exclusion criteria |
a. Eligibility for a low-risk SCT procedure
b. Evidence of a risky myelodysplastic syndrome (IPSS 3-4), defined by the presence of marrow blast excess or karyotypic abnormalities, or other primitive marrow disease
c. History of constitutional aplastic anemia (i.e. Fanconi Anemia or Dyskeratosis Congenita)
d. History of malignant tumors with active disease within 5 years from enrollment
e. Previous history of allogeneic stem cell transplantation
f. Treatment with cyclosporin A <2 weeks before enrollment
g. Treatment with G-CSF <2 weeks before enrollment
h. CMV viremia, as defined by positive PCR or pp65 test
i. WHO performance status ≥3
j. Pregnant or breast feeding patients
k. Patients with hepatic (transaminases >UNLx3 or albumin <1,5 g/L), renal (creatinine >UNLx3) or cardiac failure (ejection fraction <35%), or any other life-threatening concurrent disease (including HIV infection). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Safety will be evaluated as occurrence of adverse effects, while efficacy as overall survival, hematological response (partial and complete, including time to response) and failure free survival (failure defined as non-response, chronic treatment-maintained response or relapse). |
|
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 | 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 | Yes |
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) | 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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
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 | 3 |
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 |