Acute Lymphoblastic LeukemiaPhase 1/2SeluDexNCT03705507
International Trial of Selumetinib in Combination With Dexamethasone for the Treatment of Acute Lymphoblastic Leukaemia
A Phase 1/2 study testing Selumetinib and Dexamethasone in people with Acute Lymphoblastic Leukemia and Acute Lymphoblastic Leukemia, Adult, run by University of Birmingham at 17 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Acute Lymphoblastic Leukemia, Acute Lymphoblastic Leukemia, Adult, Acute Lymphoblastic Leukemia, Pediatric
- What is being tested?
- Selumetinib and Dexamethasone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 17 sitesin 3 countries
- Study dates
- 18 May 2018to 3 May 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Morphologically proven relapsed/refractory (M2 or M3 marrow; ≥1st relapse for adults, ≥2nd relapse in paediatric group - see Protocol Appendix 5) or progressive B cell precursor or T-Acute Lymphoblastic Leukaemia (ALL) with demonstrated RAS pathway activating mutations (NRAS, KRAS, FLT3, PTPN11, cCBL, NF1, BRAF, IKZF2, IKZF3, IL7Rα or JAK1) identified during the trial screening process
- B cell precursor patients must either:
- Have received CAR -T cell therapy, or
- Be awaiting CAR -T cell therapy, or
- Be considered ineligible for CAR -T cell therapy
- Group P (paediatric): <18 years of age; Group A (adult): ≥18 years of age
Show all 19Show fewer
- Adequate renal function:
- Group A: Serum creatinine <1.5 x upper limit of normal (ULN)
- Group P as follows:
- 5 years: Serum creatinine <0.8 mg/dL or 70 μmol/L, > 5 years but ≤ 10 years: Serum creatinine <1 mg/dL or 88 μmol/L, > 10 years but ≤ 15 years: Serum creatinine <1.2 mg/dL or 106 μmol/L, > 15 years: Serum creatinine <1.5 mg/dL or 132 μmol/L
- Patient is able to swallow selumetinib capsules whole
- Performance status (PS): Group A - Eastern Cooperative Oncology Group (ECOG) ≤2 (Protocol Appendix 6); Group P - Lansky play scale ≥60% (Protocol Appendix 7) or Karnofsky scale ≥60% (Appendix 8)
- Women of childbearing potential (see protocol section 7.9.3 for definition) must have a negative pregnancy test
- Patients who are women of childbearing potential and male patients with partners who are women of childbearing potential must agree to use appropriate contraception (see protocol section 7.9.3 for definition) whilst on trial
- Written informed consent
- Absence of any psychological, familial, sociological or geographical factors potentially hampering compliance with the trial protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
- Patients who relapse or progress after Haematopoetic Stem Cell Transplant (HSCT) need to be at least at day +100, with no signs of Graft versus Host Disease and off immunosuppressive therapy for at least one week.
- Patients who relapse or progress after CAR T cell therapy should be at least 4 weeks after infusion of CAR T cells.
- Patients must have a body surface area (BSA) ≥ 0.55 m2.
Who cannot join
- ALL without presence of RAS-pathway activating mutations
- Mature B-cell leukaemia and Philadelphia positive ALL
- Prior exposure to MEK, RAS or RAF inhibitors
- Any unresolved toxicity ≥ CTCAE Grade 2 from previous anti-cancer therapy, except for alopecia
- Cardiac conditions as follows:
- Group A and P
Show all 38Show fewer
- Prior or current cardiomyopathy including but not limited to the following:
- Known hypertrophic cardiomyopathy
- Known arrhythmogenic right ventricular cardiomyopathy
- Even if full recovery has occurred, previous moderate or severe impairment of left ventricular systolic function (LVEF <45% on Echocardiogram (ECHO) in Group A; SF <29% in Group P but excluding transient impairments due to e.g. anaemia/sepsis or results not thought to represent a true reflection of cardiac function)
- Severe valvular heart disease
- Severe congenital heart disease
- Uncontrolled hypertension:
- Group A: BP ≥150/95 mmHg despite medical therapy
- Group P: BP ≥95th percentile for age, height and gender (please refer to Blood Pressure by Age and Height Percentiles tables in Protocol Appendices 8 and 9) Group A
- Baseline (LVEF) below the lower limit of normal (LLN) or <55% measured by ECHO
- Acute coronary syndrome within 6 months prior to trial registration
- Uncontrolled Angina - Canadian Cardiovascular Society grade II-IV despite medical therapy (Protocol Appendix 11)
- Symptomatic heart failure New York Heart Association (NYHA) Class II-IV, prior or current cardiomyopathy, or severe valvular heart disease (Protocol Appendix 12)
- Atrial fibrillation with a ventricular rate >100 bpm on Electrocardiogram (ECG) at rest
- QTcF >450ms in male patients or ≥460ms in female patients, or other factors that increase the risk of QT prolongation Group P
- Baseline SF <29%
- Atrial fibrillation with a ventricular rate >130 bpm on Electrocardiogram (ECG) at rest
- QTcF >450ms in patients <12 years or ≥460ms in patients ≥12 but <18 years
- Ophthalmological conditions as follows:
- Current or past history of retinal pigment epithelial detachment (RPED)/central serous retinopathy (CSR) or retinal vein occlusion (RVO)
- Intraocular pressure (IOP) > 21 mmHg or uncontrolled glaucoma (irrespective of IOP)
- Pregnant and breast feeding females
- Known severe hypersensitivity to selumetinib, dexamethasone or combination medications or any excipient of these medicinal products, or history of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib
- Have received or are receiving an Investigational Medicinal Product (IMP) or other systemic anti-cancer treatment (not including dexamethasone, prednisolone or hydroxycarbamide) within 4 weeks (6 weeks for nitrosoureas, mitomycin, and suramin) prior to trial registration, or within a period during which the IMP or systemic anticancer treatment has not been cleared from the body (e.g. a period of 5 'half-lives'), whichever is the most appropriate and as judged by the investigator
- Have had recent major surgery within a minimum 4 weeks prior to trial registration, with the exception of surgical placement of vascular access
- Have received radiation therapy within 4 weeks prior to trial registration, or limited field of radiation for palliation within 7 days of the first dose of trial treatment
- Laboratory values as listed below (SI units):
- Serum bilirubin >1.5 x ULN (unless due to Gilbert's syndrome)
- Have evidence of any other significant clinical disorder or laboratory finding that, as judged by the investigator, makes it undesirable for the patient to participate in the trial
- Have any evidence of a severe or uncontrolled systemic disease (e.g. unstable or uncompensated respiratory, cardiac, hepatic, or renal disease, active infection (including hepatitis B, hepatitis C, HIV), active bleeding diatheses, or renal transplant)
- Have refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would adversely affect the absorption/bioavailability of the orally administered trial medication
- Any other active malignancy which, in the opinion of the investigator would limit the ability of the patient to complete the study
Trial locations and contacts
17 sites in 3 countries.
17 sites in 3 countries
United Kingdom15 sites
Queen Elizabeth Hospital
Birmingham, B15 2TH
Birmingham Children's Hospital
Birmingham, B4 6NH
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN
Alder Hey Children's Hospital
Liverpool, L12 2AP
University College Hospital Adult Unit
London, NW1 2PG
University College Hospital Paediatric/Teenage & Young Adult Unit
London, NW1 2PG
King's College Hospital
London, SE5 9RS
Hammersmith Hospital
London, W12 0HS
Great Ormond Street Hospital
London, WC1N 3JH
The Christie Hospital
Manchester, M20 4BX
Great North Children's Hospital, Royal Victoria Infirmary
Newcastle, NE1 4LP
Freeman Hospital
Newcastle, NE7 7DN
Royal Hallamshire Hospital
Sheffield, S10 2JF
Department of Paediatric Oncology, Royal Marsden Hospital, Sutton
Sutton, SM2 5PT
Haemato-Oncology Adult Unit, Royal Marsden Hospital, Sutton
Sutton, SM2 5PT
Netherlands1 site
Prinses Maxima Centrum Voor Kinderoncologie
Utrecht, 3584 CS
About this study
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
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.
Read the 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
- Being tested
- Selumetinib, Dexamethasone
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SelumetinibDrug
Also called AZD6244
Selumetinib is a small molecule inhibitor of the MEK protein
DexamethasoneDrug
Steroid used for the treatment and management of a number of conditions including cancers and leukaemias.
| Study group | Role | What they receive |
|---|---|---|
| Selumetinib + Dexamethasone - Group A (18 years and above) | Experimental | 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. Receives: Drug: Selumetinib; Drug: Dexamethasone |
| Selumetinib + Dexamethasone - Group P (under 18 years) | Experimental | 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. Receives: Drug: Selumetinib; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: The occurrence/non-occurrence of dose limiting toxicities (DLTs) in the trial defined assessment period
Measured: During cycle 1 (each cycle is 28 days)
Phase II: Response to treatment as measured by morphological response
Measured: At the end of cycle 1 (each cycle is 28 days)
Phase II: For patients with CNS involvement only response to treatment as measured by clearance of Cerebral Spinal Fluid (CSF) blasts
Measured: At the end of cycle 1 (each cycle is 28 days)
Secondary outcomes (13)
Phase I & II: The occurrence of adverse events (AEs) as measured by Common Terminology Criteria for Adverse Events (CTCAE) version 4
Measured: From cycle 1 day 1 until 28 days after End of Treatment (6 cycles, each cycle is 28 days)
Phase I & II: The occurrence of adverse events (AEs) as measured by causality assessment
Measured: From cycle 1 day 1 until 28 days after the last treatment (6 cycles, each cycle is 28 days)
Phase I & II: Pharmacokinetic variables of selumetinib in combination with dexamethasone from the concentration time profile measured by area under the plasma concentration versus time curve (AUC)
Measured: At cycle 1 day 1, cycle 1 day 4 and cycle 2 day 1 (each cycle is 28 days)
Phase I & II: Pharmacokinetic variables of selumetinib in combination with dexamethasone from the concentration time profile measured by the peak plasma concentration (Cmax)
Measured: At cycle 1 day 1, cycle 1 day 4 and cycle 2 day 1 (each cycle is 28 days)
Phase I & II: Pharmacokinetic variables of selumetinib in combination with dexamethasone from the concentration time profile measured by the time to reach peak plasma concentration (Tmax)
Measured: At cycle 1 day 1, cycle 1 day 4 and cycle 2 day 1 (each cycle is 28 days)
Phase I & II: Pharmacokinetic variables of selumetinib in combination with dexamethasone from the concentration time profile measured by the time required for the concentration of the drug to reach half of its original value (t1/2)
Measured: At cycle 1 day 1, cycle 1 day 4 and cycle 2 day 1 (each cycle is 28 days)
Phase I: Response to treatment assessed by complete remission rate as measured by morphological response in bone marrow (BM)
Measured: At the end of cycle 1 (each cycle is 28 days)
Phase I: Response to treatment assessed by complete remission rate as measured by minimal residual disease (MRD) response in BM
Measured: At the end of cycle 1 (each cycle is 28 days)
Phase I: For patients with CNS involvement only response to treatment assessed by complete remission rate as measured by clearance of CSF blasts
Measured: At the end of cycle 1 (each cycle is 28 days)
Phase I & II: Difference in pharmacokinetics of selumetinib (ΔAUC) when selumetinib is administered as single agent
Measured: At cycle 1 day 1, cycle 1 day 4 and cycle 2 day 1 (each cycle is 28 days)
Phase I & II: Difference in pharmacokinetics of selumetinib (ΔAUC) when selumetinib is administered in combination with dexamethasone
Measured: At cycle 1 day 1, cycle 1 day 4 and cycle 2 day 1 (each cycle is 28 days)
Phase II: The occurrence/non-occurrence of DLTs in the trial defined assessment period
Measured: During cycle 1 (each cycle is 28 days)
Phase II: MRD response in BM
Measured: At the end of cycle 1 (each cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2018
- Study start18 May 2018
- Primary completion3 May 2023
- Study completion3 May 2023
Why it stopped: Poor recruitment, due to a change in the standard of care for this patient population with the use of CAR-T cells
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Cancer Research UK, AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Tobias Menne, Principal investigator, The Newcastle Hospitals NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03705507
- Sponsor's protocol ID
- RG_16-186
- Other IDs
- 2016-003904-29, ISRCTN92323261, 2016
- Acronym
- SeluDex
- Status last verified
- May 2023
- First submitted
- 4 Jul 2018
- Last updated
- 11 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. The CRCTU is committed to responsible and controlled sharing of anonymised clinical trial data with the wider research community to maximise potential patient benefit while protecting the privacy and confidentiality of trial participants. Data anonymised in compliance with the Information Commissioners Office requirements, using a procedure based on guidelines from the MRC Methodology Hubs, will be available for sharing with researchers outside of the trials team within 6 months of the primary publication. More detailed information on the CRCTU's Data Sharing Policy and the mechanism for obtaining data can be found on the CRCTU website: https://www.birmingham.ac.uk/research/activity/mds/trials/crctu/index.aspx.
Publications
Menne T, Slade D, Savage J, Johnson S, Irving J, Kearns P, Plummer R, Shenton G, Veal GJ, Vormoor B, Vormoor J, Billingham L. Selumetinib in combination with dexamethasone for the treatment of relapsed/refractory RAS-pathway mutated paediatric and adult acute lymphoblastic leukaemia (SeluDex): study protocol for an international, parallel-group, dose-finding with expansion phase I/II trial. BMJ Open. 2022 Mar 4;12(3):e059872. doi: 10.1136/bmjopen-2021-059872.
PubMed 35246426
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03705507
- Acronym / sponsor ID
- SeluDex / RG_16-186
- Conditions
- Acute Lymphoblastic Leukemia, Acute Lymphoblastic Leukemia, Adult, Acute Lymphoblastic Leukemia, Pediatric, Acute Lymphoblastic Leukemia, in Relapse, Acute Lymphoblastic Leukemia Recurrent
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor recruitment, due to a change in the standard of care for this patient population with the use of CAR-T cells
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of BirminghamUniversity, hospital or other
- Collaborators
- Cancer Research UK, AstraZeneca
- Study start
- 18 May 2018 (actual)
- Primary completion
- 3 May 2023 (actual)
- Study completion
- 3 May 2023 (actual)
- First posted
- 15 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Selumetinib + Dexamethasone - Group A (18 years and above) | Experimental | Drug: Selumetinib, Drug: DexamethasonePatients 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. |
| Selumetinib + Dexamethasone - Group P (under 18 years) | Experimental | Drug: Selumetinib, Drug: DexamethasonePatients 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (19 listed)
- Morphologically proven relapsed/refractory (M2 or M3 marrow; ≥1st relapse for adults, ≥2nd relapse in paediatric group - see Protocol Appendix 5) or progressive B cell precursor or T-Acute Lymphoblastic Leukaemia (ALL) with demonstrated RAS pathway activating mutations (NRAS, KRAS, FLT3, PTPN11, cCBL, NF1, BRAF, IKZF2, IKZF3, IL7Rα or JAK1) identified during the trial screening process
- B cell precursor patients must either:
- Group P (paediatric): <18 years of age; Group A (adult): ≥18 years of age
- Adequate renal function:
- Patient is able to swallow selumetinib capsules whole
Key exclusion criteria (38 listed)
- ALL without presence of RAS-pathway activating mutations
- Mature B-cell leukaemia and Philadelphia positive ALL
- Prior exposure to MEK, RAS or RAF inhibitors
- Any unresolved toxicity ≥ CTCAE Grade 2 from previous anti-cancer therapy, except for alopecia
- Cardiac conditions as follows:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SelumetinibAlso: AZD6244Selumetinib is a small molecule inhibitor of the MEK protein | Drug | Selumetinib + Dexamethasone - Group A (18 years and above), Selumetinib + Dexamethasone - Group P (under 18 years) |
| DexamethasoneSteroid used for the treatment and management of a number of conditions including cancers and leukaemias. | Drug | Selumetinib + Dexamethasone - Group A (18 years and above), Selumetinib + Dexamethasone - Group P (under 18 years) |
Primary outcome
Phase I: The occurrence/non-occurrence of dose limiting toxicities (DLTs) in the trial defined assessment period
Time frame: During cycle 1 (each cycle is 28 days)
Phase II: Response to treatment as measured by morphological response
Time frame: At the end of cycle 1 (each cycle is 28 days)
Phase II: For patients with CNS involvement only response to treatment as measured by clearance of Cerebral Spinal Fluid (CSF) blasts
Time frame: At the end of cycle 1 (each cycle is 28 days)
13 secondary outcomes
Phase I & II: The occurrence of adverse events (AEs) as measured by Common Terminology Criteria for Adverse Events (CTCAE) version 4
Time frame: From cycle 1 day 1 until 28 days after End of Treatment (6 cycles, each cycle is 28 days)
Phase I & II: The occurrence of adverse events (AEs) as measured by causality assessment
Time frame: From cycle 1 day 1 until 28 days after the last treatment (6 cycles, each cycle is 28 days)
Phase I & II: Pharmacokinetic variables of selumetinib in combination with dexamethasone from the concentration time profile measured by area under the plasma concentration versus time curve (AUC)
Time frame: At cycle 1 day 1, cycle 1 day 4 and cycle 2 day 1 (each cycle is 28 days)
Phase I & II: Pharmacokinetic variables of selumetinib in combination with dexamethasone from the concentration time profile measured by the peak plasma concentration (Cmax)
Time frame: At cycle 1 day 1, cycle 1 day 4 and cycle 2 day 1 (each cycle is 28 days)
Phase I & II: Pharmacokinetic variables of selumetinib in combination with dexamethasone from the concentration time profile measured by the time to reach peak plasma concentration (Tmax)
Time frame: At cycle 1 day 1, cycle 1 day 4 and cycle 2 day 1 (each cycle is 28 days)
Phase I & II: Pharmacokinetic variables of selumetinib in combination with dexamethasone from the concentration time profile measured by the time required for the concentration of the drug to reach half of its original value (t1/2)
Time frame: At cycle 1 day 1, cycle 1 day 4 and cycle 2 day 1 (each cycle is 28 days)
Phase I: Response to treatment assessed by complete remission rate as measured by morphological response in bone marrow (BM)
Time frame: At the end of cycle 1 (each cycle is 28 days)
Phase I: Response to treatment assessed by complete remission rate as measured by minimal residual disease (MRD) response in BM
Time frame: At the end of cycle 1 (each cycle is 28 days)
Phase I: For patients with CNS involvement only response to treatment assessed by complete remission rate as measured by clearance of CSF blasts
Time frame: At the end of cycle 1 (each cycle is 28 days)
Phase I & II: Difference in pharmacokinetics of selumetinib (ΔAUC) when selumetinib is administered as single agent
Time frame: At cycle 1 day 1, cycle 1 day 4 and cycle 2 day 1 (each cycle is 28 days)
Phase I & II: Difference in pharmacokinetics of selumetinib (ΔAUC) when selumetinib is administered in combination with dexamethasone
Time frame: At cycle 1 day 1, cycle 1 day 4 and cycle 2 day 1 (each cycle is 28 days)
Phase II: The occurrence/non-occurrence of DLTs in the trial defined assessment period
Time frame: During cycle 1 (each cycle is 28 days)
Phase II: MRD response in BM
Time frame: At the end of cycle 1 (each cycle is 28 days)
Results and safety
The study was stopped early (reason given: Poor recruitment, due to a change in the standard of care for this patient population with the use of CAR-T cells). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2023.
- Background: PubMed 35246426Menne T, Slade D, Savage J, Johnson S, Irving J, Kearns P, Plummer R, Shenton G, Veal GJ, Vormoor B, Vormoor J, Billingham L. Selumetinib in combination with dexamethasone for the treatment of relapsed/refractory RAS-pathway mutated paediatric and adult acute lymphoblastic leukaemia (SeluDex): study protocol for an international, parallel-group, dose-finding with expansion phase I/II trial. BMJ Open. 2022 Mar 4;12(3):e059872. doi: 10.1136/bmjopen-2021-059872.
- Trial WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. The CRCTU is committed to responsible and controlled sharing of anonymised clinical trial data with the wider research community to maximise potential patient benefit while protecting the privacy and confidentiality of trial participants. Data anonymised in compliance with the Information Commissioners Office requirements, using a procedure based on guidelines from the MRC Methodology Hubs, will be available for sharing with researchers outside of the trials team within 6 months of the primary publication. More detailed information on the CRCTU's Data Sharing Policy and the mechanism for obtaining data can be found on the CRCTU website: https://www.birmingham.ac.uk/research/activity/mds/trials/crctu/index.aspx.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tobias Menne principal investigator
The Newcastle Hospitals NHS Foundation Trust
17 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Selumetinib and Dexamethasone in people with Acute Lymphoblastic Leukemia and Acute Lymphoblastic Leukemia, Adult, run by University of Birmingham at 17 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United Kingdom, Denmark, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Poor recruitment, due to a change in the standard of care for this patient population with the use of CAR-T cells). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I: The occurrence/non-occurrence of dose limiting toxicities (DLTs) in the trial defined assessment period (time frame: During cycle 1 (each cycle is 28 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03705507, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2023.