SeluDex

Phase 1

• Conditions: Relapsed/refractory acute lymphoblatic leukaemia with mutation in the RAS pathway; MedDRA version: 20.0 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-003904-29-GB
• Lead Sponsor: niversity of Birmingham

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-03-27
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 42

Inclusion Criteria

• Morphologically proven relapsed (M2 or M3 marrow; =1st relapse for adults, =2nd relapse in paediatric group) or progressive B or T-cell precursor Acute Lymphoblastic Leukaemia (ALL) with demonstrated RAS pathway activating mutations (NRAS, KRAS, FLT3, PTPN11, cCBL) identified during the trial screening process
• Group P (paediatric): <18 years of age; Group A (adult): =18 years of age
• Adequate renal function, with Serum creatinine >1.5 x upper limit of normal (ULN) for Group A and as follows for for Group P
o =< 5 years: <0.8 mg/dL or 70 µmol/L
o > 5 years but =< 10 years: <1 mg/dL or 88 µmol/L
o > 10 years but =< 15 years: <1.2 mg/dL or 106 µmol/L
o > 15 years: <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 (Appendix 5); Group P - Lansky play scale =60% (Appendix 6) or Karnofsky scale =60% (Appendix 7)
• Female patients post menarche: negative pregnancy test
• Sexually active participants must agree to use appropriate contraception 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 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
Are the trial subjects under 18? yes
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 11
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

• 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:
o Uncontrolled hypertension: Group A: BP =150/95 mmHg despite medical therapy; Group P: please refer to Blood Pressure by Age and Height Percentiles tables (Appendices 8 and 9)
o Acute coronary syndrome within 6 months prior to trial registration
o Uncontrolled Angina - Canadian Cardiovascular Society grade II-IV despite medical therapy (Appendix 10)
o Symptomatic heart failure New York Heart Association (NYHA) Class II-IV, prior or current cardiomyopathy, or severe valvular heart disease (Appendix 11)
o Prior or current cardiomyopathy including but not limited to the following:
• Known hypertrophic cardiomyopathy
• Known arrhythmogenic right ventricular cardiomyopathy
o Previous moderate or severe impairment of left ventricular systolic function (LVEF <45% on ECHO in Group A; SF <29% in Group P) even if full recovery has occurred
o Severe valvular heart disease
o Group A: Baseline (LVEF) below the lower limit of normal (LLN) or <55% measured by ECHO for Group A; Baseline SF <29% for Group P
o Atrial fibrillation with a ventricular rate >100 bpm on Electrocardiogram (ECG) at rest
o QTcF >450ms in male patients or =460ms in female patients, or other factors that increase the risk of QT prolongation
• Ophthalmological conditions as follows:
o Current or past history of retinal pigment epithelial detachment (RPED)/central serous retinopathy (CSR) or retinal vein occlusion
o 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 IMP or other systemic anti-cancer treatment (not including dexamethasone 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):
o 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified