Condition or disease | Intervention/treatment | Phase |
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Acute Lymphoblastic Leukemia Acute Lymphoblastic Leukemia, Adult Acute Lymphoblastic Leukemia, Pediatric Acute Lymphoblastic Leukemia, in Relapse Acute Lymphoblastic Leukemia Recurrent | Drug: Selumetinib Drug: Dexamethasone | Phase 1 Phase 2 |
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.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 42 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Intervention Model Description: | Group P will enrol all patients under 18 years of age and Group A will enrol all patients who are 18 years or older. |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | 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 |
Actual Study Start Date : | May 18, 2018 |
Estimated Primary Completion Date : | December 2021 |
Estimated Study Completion Date : | May 2022 |
Arm | Intervention/treatment |
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Experimental: Selumetinib + Dexamethasone - Group A (18 years and above)
Patients will receive the adult cohort specified dose of selumetinib by mouth, as a single dose on cycle 1 day 1, then twice daily continuously from cycle 1 day 4 onwards. Combined with pulsed doses of dexamethasone at 6mg/m2/day on days 2-4 and 8-11 then at 4mg/m2/day on days 15-18 and 22-25 divided into two doses (as per local practice) by mouth during cycle 1, then on days 1-4 at 4mg/m2/day at the start of cycle 2, then on days 1-5 at 6mg/m2/day during subsequent cycles.
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Drug: Selumetinib
Selumetinib is a small molecule inhibitor of the MEK protein
Other Name: AZD6244
Drug: Dexamethasone Steroid used for the treatment and management of a number of conditions including cancers and leukaemias.
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Experimental: Selumetinib + Dexamethasone - Group P (under 18 years)
Patients will receive the paediatric cohort specified dose of selumetinib by mouth, as a single dose on cycle 1 day 1, then twice daily continuously from cycle 1 day 4 onwards. Combined with pulsed doses of dexamethasone at 6mg/m2/day on days 2-4 and 8-11 then at 4mg/m2/day on days 15-18 and 22-25 divided into two doses (as per local practice) by mouth during cycle 1, then on days 1-4 at 4mg/m2/day at the start of cycle 2, then on days 1-5 at 6mg/m2/day during subsequent cycles.
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Drug: Selumetinib
Selumetinib is a small molecule inhibitor of the MEK protein
Other Name: AZD6244
Drug: Dexamethasone Steroid used for the treatment and management of a number of conditions including cancers and leukaemias.
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Ages Eligible for Study: | Child, Adult, Older Adult |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Adequate renal function:
Group P as follows:
Exclusion Criteria:
Group A and P
Prior or current cardiomyopathy including but not limited to the following:
Uncontrolled hypertension:
Ophthalmological conditions as follows:
Laboratory values as listed below (SI units):
Contact: Sarah Johnson | +441214146754 | seludex@trials.bham.ac.uk | |
Contact: Joshua Savage | +441214158421 | seludex@trials.bham.ac.uk |
Principal Investigator: | Tobias Menne | The Newcastle Hospitals NHS Foundation Trust |
Tracking Information | |||||||||
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First Submitted Date ICMJE | July 4, 2018 | ||||||||
First Posted Date ICMJE | October 15, 2018 | ||||||||
Last Update Posted Date | January 19, 2021 | ||||||||
Actual Study Start Date ICMJE | May 18, 2018 | ||||||||
Estimated Primary Completion Date | December 2021 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | ||||||||
Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
Current Other Pre-specified Outcome Measures |
Exploratory pharmacodynamic biomarker studies including levels of phosphorylated Extracellular signal-regulated kinase (ERK) by flow cytometry as well as retrospective messenger ribonucleic acid (mRNA) profiling, including Bcl-2-like protein 11 (BIM) [ Time Frame: Cycle 1 day 1, cycle 1 day 4 and End of Treatment (6 cycles, each cycle is 28 days) ] | ||||||||
Original Other Pre-specified Outcome Measures | Same as current | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | International Trial of Selumetinib in Combination With Dexamethasone for the Treatment of Acute Lymphoblastic Leukaemia | ||||||||
Official Title ICMJE | 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 | ||||||||
Brief 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. |
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Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Phase 1 Phase 2 |
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Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Parallel Assignment Intervention Model Description: Group P will enrol all patients under 18 years of age and Group A will enrol all patients who are 18 years or older. Masking: None (Open Label)Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE |
42 | ||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||
Estimated Study Completion Date ICMJE | May 2022 | ||||||||
Estimated Primary Completion Date | December 2021 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
Group A and P
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Sex/Gender ICMJE |
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Ages ICMJE | Child, Adult, Older Adult | ||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | Netherlands, United Kingdom | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT03705507 | ||||||||
Other Study ID Numbers ICMJE | RG_16-186 2016-003904-29 ( EudraCT Number ) ISRCTN92323261 ( Registry Identifier: ISRCTN ) |
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Has Data Monitoring Committee | Yes | ||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | University of Birmingham | ||||||||
Study Sponsor ICMJE | University of Birmingham | ||||||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | University of Birmingham | ||||||||
Verification Date | January 2021 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |