Predictive value of ABCB1 genotypes on dose adjustment of imatinib in patients with GIST (Gastro-Intestinal Stromal Tumour) and CML (Chronic Myeloid Leukaemia)

Predictive value of ABCB1 genotypes on dose adjustment of imatinib in patients with GIST(Gastro-Intestinal Stromal Tumour) and CML (Chronic Myeloid Leukaemia)

Status

Not yet recruiting

Phases

Unknown

Study type

Observational

Source

ANZCTR

Registry ID

ACTRN12606000117516

Enrollment

300

Registered

2006-04-03

Start date

2006-04-10

Completion date

Unknown

Last updated

2020-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

The purpose of this study is to examine the genotypes of ABCB1 (a type of gene found in your cells) in a larger group of patients to test whether the correlation (matching of genes with more side effects from drug treatment) seen in the previous small study are true. The primary (main) endpoint will be a correlation of ABCB1 genotype and imatinib dose after three months of therapy that will allow for dose adjustments based on toxicity (side effects). The larger patient numbers will also allow a haplotype (gene) analysis to be done. The importance of dose individualisation is illustrated by studies that show better outcomes for cancer patients who have post-treatment dose adjustments based on therapeutic drug monitoring or on toxicity. However, with these methods, the optimum dose for each patient is often not reached until after the majority of the treatment course has been given. A correlation between ABCB1 genotype and toxicity-adjusted dose has practical significance since a simple blood test could allow effective dose selection in individuals. Approximately 300 patients will be required.

Interventions

The study will correlate the toxicity-adjusted dose of imatinib after 3 months of therapy with polymorphisms of drug elimination genes, particularly ABCB1 (MDR1). Patients will be asked to give a single blood sample for genotyping (at any time) and we will collect clinical data on dose and toxicity retrospectively from medical records.

Eligibility

Sex/Gender

All

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

ECOG 0, 1 or 2 at start of treatment with imatinib• Medication records of the first 3 months ± 14 days of treatment must be available • Starting dose needs to be either greater than or equal to 600 mg or starting dose of 400 mg if there was a dose reduction required due to toxicity within the first 3 months period of treatment with imatinib• No chemotherapy, biological treatment or any other investigational drug within 28 days of treatment start• Adequate haematological function as determined within the preceeding14 days, ANC >/= 1.5 x109/l as well as Platelets >/= 100 x109/l• Adequate liver and renal function defined as serum bilirubin concentration less than 1.5 x ULN, AST and ALT less than 2.5 x ULN, serum creatinine concentration less than 1.5 x ULN• No known primary liver disease and no other severe or uncontrolled concurrent medical condition within the first 3 months of treatment with imatinib.• Patients who have participated on other clinical studies of imatinib will be suitable for this study.• Being treated with Imatinib for more than 10 weeks • Signed informed consent.

Exclusion criteria

Patients who are unable to sign informed consent• Patients who have had less than 400 mg of imatinib at start of treatment• Patient included in the initial Glisest study • Patients unable to give blood• Patients who had a bone-marrow-transplantation prior to imatinib treatment• Patients who had no blood sample taken and available for genotyping prior to bone-marrow-transportation.

Outcome results