UKALL14 - A randomized trial for adults with newly diagnosed acute lymphoblastic leukemia
University College London
The UKALL14 trial is designed to improve treatment options for adult patients with Acute Lymphoblastic Leukemia (ALL) who currently have high relapse rates and poor disease-free survival following treatment compared to paediatric ALL patients. Treatment for ALL is complicated and usually involves 2-3 years of chemotherapy (initial intensive, in-patient treatments known as induction, intensification and consolidation, followed by outpatient treatments, known as maintenance) OR induction therapy can be followed straight away by bone marrow transplantation. Who should have a bone marrow transplant is a matter of debate. However, bone marrow transplant is a commonly used treatment option.Several discrete questions addressing different aspects of the therapy will be assessed during this trial. The trial protocol necessarily incorporates all the complex elements that any patient with ALL will undergo but most of the treatment contained within the trial protocol schedule would be part of a standard treatment regimen. Below the specific trial questions and who will be eligible to participate for each question are listed: 1. adults in the UK (>25 years and < than 65 years of age) with newly diagnosed B and T lineage ALL will be eligible. All will be treated with a standard initial induction chemotherapy with the addition of a newer version of a standard drug (Pegylated Asparaginase). Careful information on the toxicity of this drug will be part of the study.2. study entrants will be eligible to participate in an initial randomisation to receive a new drug along with standard initial treatment known as "induction". In all cases, the control arm will consist of patients receiving standard treatment without any additional drugs.For patients with B-lineage ALL the randomisation will be to receive standard treatment with additional monoclonal antibodies: anti CD20 (rituximab)/anti CD22 (epratuzumab)/both anti CD20 and anti CD22. The main question being asked is does the addition of these new agents improve outcome, as measured by Event Free Survival (EFS). For patients with T-lineage ALL, the new drug will be Nelarabine. Patients will be randomised to standard therapy alone or standard therapy followed by Nelarabine to assess improvement in outcome.3. Risk stratified unrelated bone marrow transplant will be undertaken for all patients deemed to be at high risk of relapse. For all patients in complete remission following induction therapy their risk of relapse will be assessed using a risk score based on information from previous studies of ALL. patients with one or more high risk features will be assigned to allogeneic bone marrow transplantation. The study will examine whether those who do not have a sister or brother to act as a donor can benefit from using a matched unrelated stem cell donor from the donor registries. For those over the age of 40, in whom a standard allogeneic transplant is too toxic, a more gentle way of doing a transplant known as 'reduced intensity conditioning' will be investigated.Paients at standard risk who do not have a sibling donor will continue with standard chemotherapy, known as consolidation and maintenance. If patients have a sibling donor, and are less than 40 they can continue with a sibling allogeneic transplant as our previous study showed this was the treatment with the best outcome.4. We are going to ask a question which addresses the toxicity of allogeneic transplant. All patients assigned to a standard allogeneic bone marrow transplant will be eligible to participate in a randomised comparison between 2 dosing schedules of a drug known to reduce the mucosal toxicity (very sore mouth, sore throat, abdominal pain, diarrhoea) of the transplant regimen. The randomisation will be to determine whether giving Palifermin in a shorter 'collapsed' schedule will be as effective as the typical schedule. This means all patients will get the drug - only the timing of the doses will be different between the 2 arms. The trial will be conducted in hospitals in the UK and Eire, those that do not have transplant facilities will refer patients to their nearest participating transplant centre at that stage of the trial.The trial is aiming to recruit 960 patients in 6 years and will follow up patients until death to capture any late effects of transplant.
London - Fulham Research Ethics Committee
Date of REC Opinion
13 Jan 2010
Further Information Favourable Opinion