NCT03705507

International Trial of Selumetinib in Combination With Dexamethasone for the Treatment of Acute Lymphoblastic Leukaemia

International Phase I/II Expansion Trial of the MEK Inhibitor Selumetinib in Combination With Dexamethasone for the Treatment of Relapsed/Refractory RAS-pathway Mutated Paediatric and Adult Acute Lymphoblastic Leukaemia

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: University of Birmingham · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

This trial is to investigate the combination of selumetinib and dexamethasone in the treatment of acute lymphoblastic leukaemia (ALL) in both adults and children. Phase I is to find the most suitable dose of selumetinib to safely give with dexamethasone. Phase II will use this dose to find out how well the combination works.

Detailed description

Acute lymphoblastic leukaemia (ALL) is the most common childhood cancer worldwide. The overall newly diagnosed ALL cure rate is approaching 90% however children with relapsed ALL often do not survive. The frequency of ALL in adults is significantly lower however more challenging to treat compared to childhood ALL. Adult ALL is more resistant to chemotherapy and patient have reduced treatment tolerance (particularly the elderly population) therefore overall survival rates are low. Therefore there is a need to develop more effective treatment which improves survival rates for this patient population. Those eligible in the paediatric setting are in their second or further relapse, often after a previous allogeneic stem cell transplant (SCT), and usually in a palliative situation. Adult patients who are not suitable for more intensive therapy can enter the trial in first relapse. The trial offers an out-patient based treatment approach of this heavily pre-treated patient group. The trial includes patients with B-cell precursor and T-ALL irrespective of Central Nervous System (CNS) disease status.CNS positive patients and patients with T-ALL are usually excluded from other early phase clinical trials. If treatment is successful, patients could continue with other therapies/trials once complete remission achieved (e.g. Chimeric Antigen Receptor (CAR) T cell therapy). Selumetinib is a small molecule inhibitor of MEK, a protein in the RAS-pathway. Mutations in genes in the RAS pathway have been found in a large proportion of patients with ALL. Selumetinib targets this over-activated pathway to arrest cancer cell growth. Dexamethasone is a steroid important in the treatment of leukaemia to stimulate the death of cancer cells. The SeluDex trial is for patients with relapsed or refractory RAS-pathway mutated ALL. The primary objective of this trial in Phase I is to see what dose of selumetinib can safely be given in combination with dexamethasone in participants. During Phase II, the primary objective is to assess the preliminary information regarding the effectiveness of this combined treatment.

Conditions

• Acute Lymphoblastic Leukemia
• Acute Lymphoblastic Leukemia, Adult
• Acute Lymphoblastic Leukemia, Pediatric
• Acute Lymphoblastic Leukemia, in Relapse
• Acute Lymphoblastic Leukemia Recurrent

Interventions

Type	Name	Description
DRUG	Selumetinib	Selumetinib is a small molecule inhibitor of the MEK protein
DRUG	Dexamethasone	Steroid used for the treatment and management of a number of conditions including cancers and leukaemias.

Timeline

• Start date: 2018-05-18
• Primary completion: 2023-05-03
• Completion: 2023-05-03
• First posted: 2018-10-15
• Last updated: 2023-05-11

Locations

17 sites across 3 countries: Denmark, Netherlands, United Kingdom