E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of Acute Graft-versus-Host Disease (aGvHD) after allogeneic hematopoietic stem cell transplant |
|
E.1.1.1 | Medical condition in easily understood language |
Prevention of Acute Graft-versus-Host Disease (aGvHD) |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068908 |
E.1.2 | Term | AGVHD |
E.1.2 | System Organ Class | 100000004870 |
|
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 primary objective of the study is to compare the efficacy of defibrotide added to standard of care immunoprophylaxis vs standard of care immunoprophylaxis alone for the prevention of acute graft-versus-host disease (aGvHD) as measured by the cumulative incidence of Grade B-D by Day +100 post-allogeneic hematopoietic stem cell transplant (HSCT) in adult and pediatric patients. |
|
E.2.2 | Secondary objectives of the trial |
•To compare the efficacy of defibrotide added to standard of care immunoprophylaxis vs standard of care immunoprophylaxis alone on additional variables:
-Grade B-D aGvHD-free survival by Days +100 and +180 post-HSCT
-Cumulative incidence of Grade B-D aGvHD by Day +180 post-HSCT
-Cumulative incidence of Grade C-D aGvHD by Days +100 and +180 post-HSCT
-Cumulative incidence of relapse by Days +100 and +180 post-HSCT
•To evaluate steroid use in the treatment of aGvHD by Day +180 post-HSCT
•To compare the health-related quality of life (HRQoL) using the following questionnaires:
-FACT-BMT-TOI (adults only)
-EuroQoL-5D (EQ-5D; version dependent on age group)
•To compare the safety of defibrotide added to standard of care immunoprophylaxis vs standard of care immunoprophylaxis alone, including AE profile, SAE profile, laboratory abnormalities, neutrophil and platelet engraftment, graft failure, and infection.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient must be ≥1 year of age at screening and undergoing
allogeneic HSCT.
2. Patient must be diagnosed with acute leukemia in morphologic
complete remission (CR1 or CR2) or with MDS with no circulating blasts
and with less than 5% blasts in the bone marrow
3. Patient must have planned to receive either a myeloablative or
reducedintensity conditioning regimen and have an unrelated donor who
is HLA matched or single-allele mismatched
4. Graft must be a CD3+ T-cell replete PBSC graft or non-manipulated BM
graft.
5. Adult patients must be able to understand and sign a written informed
consent. For pediatric patients, the parent/legal guardian or
representative must be able to understand and sign a written informed
consent. Assent, when appropriate, will be obtained according to
institutional guidelines. |
|
E.4 | Principal exclusion criteria |
1. Patient has had a prior autologous or allogeneic HSCT.
2. Patient is using or plans to use an investigational agent for the
prevention of GvHD.
3. Patient is receiving or plans to receive other investigational therapy
4. Patient, in the opinion of the investigator, may not be able to comply
with the safety monitoring requirements of the study.
5. Patient has a psychiatric illness that would prevent the patient or
legal guardian or representative from giving informed consent and/or
assent.
6. Patient has a serious active disease or co-morbid medical condition, as
judged by the investigator, which would interfere with the conduct of
this study.
7. Patient is pregnant or lactating and does not agree to stop
breastfeeding.
8. Any other condition that would cause a risk to the patient if he/she
participated in the trial.
9. Patient has a known history of hypersensitivity to defibrotide or any of
its excipients. Patient has a known hypersensitivity to any agent(s) or
excipients of agent(s) within patient's planned immunoprophylaxis
regimen. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint of this study is cumulative incidence of Grade B-D aGvHD by Day +100 post-HSCT. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints include the following:
• Grade B-D aGvHD-free survival by Days +100 and +180 post-HSCT
• Cumulative incidence of Grade B-D aGvHD by Day +180 post-HSCT
• Cumulative incidence of Grade C-D aGvHD by Days +100 and +180 post-HSCT
• Cumulative incidence of relapse by Days +100 and +180 post-HSCT |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day +100 and +180 post-HSCT for endpoints except for Cumulative incidence of Grade B-D aGvHD: Day +180 post-HSCT only |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
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 | Yes |
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 | Yes |
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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 42 |
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 | No |
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 |
Austria |
Belgium |
Bulgaria |
Canada |
Croatia |
France |
Germany |
Greece |
Italy |
Poland |
Portugal |
Spain |
United Kingdom |
United States |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 24 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 24 |
E.8.9.2 | In all countries concerned by the trial days | 0 |