E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Lymphoblastic Leukaemia (ALL) |
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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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000844 |
E.1.2 | Term | Acute lymphoblastic leukaemia |
E.1.2 | System Organ Class | 100000004864 |
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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 principle objective of the trial is to determine whether there is a difference in the disease free survival (DFS) of patients with ALL after a TBI and cyclophosphamide transplant compared with patients receiving the standard fludarabine/melphalan transplant regimen. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are are to determine whether there is a difference between overall survival, cumulative incidence of disease relapse, non relapse mortality, incidence of grade 2-4 acute GvHD, incidence of chronic GvHD of any grade, occurrence and severity of veno-occlusive disease, duration of hospitalisation in the first year and quality of life (QoL), full donor chimerism at day 100 and TBI related symptomatic pulmonary toxicity between the two treatment groups. |
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E.2.3 | Trial contains a sub-study | No |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Multi-lineage chimerism and molecular MRD. Bone marrow samples - every 3 months measure MRD levels and multi-lineage |
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E.3 | Principal inclusion criteria |
Patients with morphologically documented ALL who meet the following criteria; • Patients between the ages of 40-65 years. NB: Patients under the age of 40 who are considered unsuitable for a myeloablative transplant may enrol onto the trial following discussion with the CI via the Trials Office • Patients with ALL in first CR • Availability of a human leukocyte antigen (HLA) identical sibling or suitable matched unrelated donor (suitable matched defined as no greater than a single allele mismatch at HLA A, B, C or DRβ1). A single allele mismatch is permitted if there are adverse cytogenetics or MRD positivity at any timepoint • Patients considered suitable to undergo a RIC allogeneic SCT as clinically judged by the Local Investigator including:- o Adequate hepatic and renal function as determined by full blood count and biochemistry assessment o Resolution of any toxic effects of prior therapy (including radiotherapy, chemotherapy or surgical procedures). Patients with bone marrow suppression following therapy may enter the trial o Patients with abnormal cardiac and/or pulmonary function must be considered fit for allogeneic SCT including 8Gy of TBI at the time of randomisation. • Patients with an ECOG performance status 0,1 or 2 • Female of and male patients of reproductive potential(i.e. not post-menopausal or surgically sterilised) must use appropriate, highly effective, contraception from the point of admission for transplant conditioning therapy until 12 months after transplant • Patients have given written informed consent • Patients willing and able to comply with scheduled study visits and laboratory tests
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E.4 | Principal exclusion criteria |
• Patients with contraindications to receiving RIC allogeneic SCT • Female patients who are pregnant or breastfeeding. All women of childbearing potential (WOCBP) must have a negative pregnancy test before commencing treatment • Adults of reproductive potential not willing to use appropriate, effective, contraception during the specified period • Patients with renal or hepatic impairment as clinically judged by Local Investigator • Patients with active infection, HIV-positive or chronic active Hep-A or –C • Patients with concurrent active malignancy. Patients with a previous history of malignancy can be included if that malignancy is considered to be at a low risk of recurrence
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E.5 End points |
E.5.1 | Primary end point(s) |
To determine the disease free survival (DFS) of patients with acute lymphoblastic leukaemia (ALL) after a total body irradiation and cyclophosphamide allograft compared with patients using fludarabine and melphalan reduced intensity conditioning regimen. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Patients will be followed up for 36 months to assess disease free survival |
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E.5.2 | Secondary end point(s) |
To compare transplant outcome between the control and experimental arm in terms of overall survival (OS, Cumulative incidence of relapse (CIR), Non relapse mortality (NRM), incidence of Grade 2-4 acute GvHD, incidence of chronic GvHD of any grade, occurrence and severity of veno-occlusive disease (VOD), duration of hospitalisation in the first year, quality of life (QoL), full donor chimerism at Day 100 and TBI related symptomatic pulmonary toxicity following allogeneic transplantation. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Patients will be followed up for 36 months to assess the secondary endpoints of the study. |
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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 | 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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 22 |
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 | 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
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The end of the trial will be the last patients's last follow-up visit (i.e. month 60 visit) |
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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 | 7 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
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 | 1 |