| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 15.1 |
| E.1.2 | Level | HLT |
| E.1.2 | Classification code | 10018847 |
| E.1.2 | Term | Haematological disorders |
| E.1.2 | System Organ Class | 100000004851 |
|
| 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 assess the safety and efficacy of unrelated donor umbilical cord blood transplantation (UCBT) in a multi-institution UK setting where the use a myeloablative preparative regimen is indicated. The anti-malignancy effect of this treatment is achieved by a combination of intensive chemoradiotherapy and the 'graft vs. malignancy' (GVM) effect. The advantage of this approach is the increased likelihood of destroying the malignant cells and a reduced risk of graft rejection as the bone marrow is better prepared to accept the transplant than with reduced intensity conditioning. However, the treatment may be less well tolerated by some patients and therefore patients of advanced age or with impaired organ function are not eligible for this trial. |
|
| E.2.2 | Secondary objectives of the trial |
1) to assess the safety and efficacy of this approach in children
2) to assess the way in which the immune system recovers after UCBT using a myeloablative regimen
3) to assess the relative contribution of recipient and donor bone marrow function 21 days post-transplant
4) To assess transplant related mortality associated with myeloablative UCBT at day 100 post-transplant
5) To assess the incidence of grades II-IV and III-IV acute graft-versus-host disease (GVHD)
6) To assess the risk of relapse and progressive disease at 1 year post-transplant after myeloablative UCBT
7) To assess overall and progression-free survival at 1 year after myeloablative UCBT |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) Age 45 years or younger. Children under the age of 2 years are at an increased risk of long term complications of total body irradiation (TBI) and will therefore not recieve TBI (AML patients aged <16 years will also not receive TBI as chemotherapy-only conditioning is now accepted national practice for this population).
. The risk of haemopoietic stem cell transplantation increases with increasing age. Furthermore the myeloablative treatment regimen may be less well tolerated by some patients and therefore patients of advanced age or with impaired organ function are not eligible for this trial. Therfore the upper age limit of 45 years was chosen by consensus of leading UK transplant physicians for reasons of safety.
2) Umbilical cord blood graft available with an adequate cell dose and HLA match. The rates of engraftment and survival following umbilical cord blood transplantation are determined by the cell dose (total number of nucleated cells given to the patient) and the closeness of HLA match. A strict algorithm for unit selection will be used based on currently available data. Units selected for every patient will be approved by the 'cord blood selection committee' (CBSC) to ensure consistency and safety.
3) Disease for which an allogeneic haemopoietic stem cell transplant (HSCT) is indicated. The disease type and remission status of every patient will comply with internationally agreed criteria.
4) The individual patient's disease status is such that there is no alternative therapy likely to achieve cure or provide a significant prolongation of disease-free survival. These patients would have proceeded to a conventional transplant if a blood or marrow donor had been identified.
5) Adequate organ function & performance status. Strict criteria for adequate organ function will be used to optimise safety of the procedure. The criteria used in this protocol are more stringent than those used by the University of Minnesota to improve safety further. |
|
| E.4 | Principal exclusion criteria |
1) Availability of a conventional related or unrelated haemopoietic stem cell donor within an acceptable time period. Such donors represent the standard of care in UK transplantation and must remain the first choice where available.
2) Current active serious infection. The preparative regimen results in profound suppression of the white count and immune system. Patients with active serious infection, such as invasive fungus, could develop life-threatening infection after transplant and will therefore be excluded.
3) Previous irradiation that precludes the safe administration of 13.2Gy- 14.4Gy of total body irradiation (TBI) in patients over 2 years of age and AML patients over the age of 16. Every patient scheduled to recieve TBI will be reviewed by a radiation oncologist to ensure that this dose of TBI will be safe. Children under the age of 2 years are at an increased risk of long term complications and will therefore not recieve TBI (AML patients aged <16 years will also not receive TBI as chemotherapy-only conditioning is now accepted national practice for this population).
4) Prior autograft. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary end-point of this study is non-relapse mortality at day 100. |
|
| 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 | 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 | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 24 |
| 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
|
| Last follow up visit by last subject undergoing the trial (2years after final patient is recruited) |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| 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 |
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