Relapsed and refractory acute leukaemia MedDRA version: 14.1 Level: PT Classification code 10000830 Term: Acute leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: AT9283 (as the free base of the L-lactate salt)
Product Code: AT9283 (as the free base of the L-lactate salt)
Pharmaceutical Form: Powder for solution for
Sponsors
Cancer Research UK
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Morphologically proven acute leukaemia For acute lymphoblastic leukaemia (ALL), patients must be in second relapse or refractory to induction therapy for first relapse or be in third or subsequent relapse. For acute myeloid leukaemia (AML), patients must be in second or subsequent relapse or refractory to an induction therpay for first relapse or otherwise without a curative treatment option. For any other type of acute leukaemia, patients must be in first or subsequent relapse or refractory to induction therapy and must not be eligible for any therapy of higher curative potential. Patients with Chronic Myeloid Leukaemia (CML) are not eligible. For all groups, patients in relapse must have greater than or equal 5% blasts in the bone marrow. Patients with refractory disease following induction must have greater than or equal to 20% blasts in the bone marrow and no evidence of CNS disease. 2. Life expectancy of at least 8 weeks 3. Karnofsky / Lansky Play scale =50% 4. Biochemical indices within the ranges shown below. These measurements must be performed within one week (Day -7 to Day -1) before the patient starts treatment. Laboratory Test Value required Serum bilirubin 6 months to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. CML 2. Cytotoxics, vincristine, anti-neoblastics within two weeks. One week for investigational medicinal products (except antibodies, for which a four week window must be observed); one week for protein kinase inhibitors and Intrathecal therapy before treatment. Any patient with ALL experiencing a rapid rise in blast count prior to starting study drug may have oral dexamethasone (6mg/m2/day) for a maximum of five days duration. AT9283 administration may be commenced once steroids have started, however steroids may NOT be started once AT9283 has started. Hydroxycarbamide 10-20mg/kg/day (or according to local practice) may be given for two days preceding the start of treatment with AT9283 in patients with AML and hyperleucocytosis. 3. No evidence of CNS disease 4. Prior exposure to an aurora kinase inhibitor. 5. Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator and the DDO should not exclude the patient. 6. Pregnant or lactating women are excluded. Female patients with the ability to become pregnant who have a negative serum or urine pregnancy test before enrolment and agree to use two of the following three highly effective forms of combined contraception (oral, injected or implanted hormonal contraception and condom, have a intra-uterine device and condom, diaphragm with spermicidal gel and condom) from the time of consent, during the trial and for six months afterwards are considered eligible. 7. Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception [condom plus spermicide] during the trial and for six months afterwards). Men with pregnant or lactating partners should be advised to use barrier method contraception (for example, condom plus spermicidal gel) to prevent exposure to the foetus or neonate. 8. Major thoracic or abdominal surgery from which the patient has not yet recovered. 9. At high medical risk because of non-malignant systemic disease including active uncontrolled infection. Current unstable or uncompensated respiratory or cardiac condition that makes it undesirable for the patient to participate. 10. Known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV). 11. Fractional shortening of =29% on Echocardiogram 12. Previous anthracycline treatment with a cumulative dose equal to or greater than 450mg/m2 doxorubicin equivalent 13. Uncontrolled arterial hypertension, defined as a systolic and / or diastolic blood pressure greater than or equal to the 95th percentile for age and height according to the graphs in Figure 2 of the protocol. 14. Congenital heart disease, with the exception of patent foramen ovale or small muscular ventricular septal deficit (within the first year of life). 15. Active graft vs host disease 16. Patients experiencing significant toxicity following haematopoietic Stem Cell Transplant (HSCT) 17. Any other condition which in the Investigator’s opinion would not make the patient a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1) To recommend a dose of AT9283 for Phase II evaluation in paediatric patients with acute leukaemia ; Secondary Objective: 1) To evaluate the safety and tolerability of AT9283 given by intravenous (IV) infusion in paediatric patients with acute leukaemia 2) To document possible evidence of efficacy of AT9283 in paediatric patients with acute leukaemia 3) To investigate the pharmacokinetic (PK) profile of AT9283 in plasma in paediatric patients with acute leukaemia ;Primary end point(s): Identify a dose level for Phase II exploration;Timepoint(s) of evaluation of this end point: 3 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Determining causality of adverse events to AT9283 and grading severity according to NCI CTCAE Version 4.02 2) Identifying Partial remission, Complete remission or Complete remission with incomplete bone marrow recovery using disease specific criteria based upon absolute neutrophil count (ANC), platelets and % blasts in the bone marrow. 3) Measurement of plasma concentrations of AT9283 in paediatric patients with acute leukaemia ;Timepoint(s) of evaluation of this end point: 3 years | — |
Countries
United Kingdom
Contacts
Public ContactDrug Development Office
Cancer Research UK
Outcome results
None listed