Acute Lymphoblastic Leukemia
Conditions
Interventions
Trade Name: Lanvis (6-thioguanine)
Pharmaceutical Form:
Trade Name: Puri-nethol (6-mercaptopurine)
Pharmaceutical Form:
INN or Proposed INN: MERCAPTOPURINE
CAS Number: 50-44-2
Concentration unit: m
Sponsors
Bonkolab, Rigshospitalet
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Male and female patients of all ethnicities meeting all the following criteria will be considered eligible for study participation: 1. Confirmed diagnosis with SR/IR-ALL, treated in accordance with NOPHO ALL 2008 protocol. 2. Patients aged 1-45 years at the time of diagnosis. 3. Bilirubin 0.5 or INR 1.5 x109/L, ANC > 0.5 x109/L and TBC > 50 x109/L within 1 week prior to inclusion. 5. Subject, if female of childbearing potential (defined as post menarche), must present with a negative pregnancy test and must be non-lactating. 6. Sexually active females and males must use accepted safe contraception (OCPs, IUD, transdermal hormonal patch, vaginal hormonal ring or subdermal hormonal implants for women and condom for men) during therapy and until three months after study exit/early termination. 7. No live vaccines given within 3 months prior to inclusion. 8. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. 9. Whenever appropriate, the child should participate in the oral and written informed consent process together with the parents. Involving the child in discussions and the decision-making process respects their emerging maturity. This process will be conducted with enough time and at the same time as obtaining the consent from the parents or the legal representative, so that the informed consent reflects the presumed will of the minor, in accordance with Article 4(a) of the Clinical Trial Directive. 10. If the study participant is unable to provide legally binding consent subject's legally authorized representative (e.i. both parent, legal guardian) must voluntarily sign and date a parental permission/ Informed Consent that is approved by the Danish Ethical Committee(EC). The subject must sign an EC approved assent, before undergoing any protocol specific procedures or assessments according to Ethical considerations for clinical trials on medicinal products conducted with the paediatric population Directive 2001/20/EC1, ICH/GCP guidelines, and the Helsinki II Declaration. Are the trial subjects under 18? yes Number of subjects for this age range: 25 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients with negative minimal residual disease at treatment day 29 (counted from diagnosis), since these patients have an excellent prognosis on current therapy). 2. Any clinical suspicion of relapse or disease progression on routine imaging or in laboratory results. 3. Previous sinusoidal obstruction syndrome (SOS) / veno-occlusive disease (VOD) 4. Allergic hypersensitivity towards any ingredients in the three medicinal products used in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To explore the feasibility of 6TG as a supplement to maintenance2 therapy to improve the existing dose adjustment strategies. We hypothesize that MTX/6MP/6TG combination therapy will achieve a higher DNA-TGN level and enhance the effect of 6MP. We will describe toxicities, hematology and thiopurine metabolite levels during MTX/6MP/6TG combination therapy. This study will be the first to assess the applicability of 6TG in combination with standard MTX/6MP maintenance 2 therapy. ;Secondary Objective: Not applicable;Primary end point(s): Dynamic change in DNA-TGN levels after addition of 6TG to therapy.;Timepoint(s) of evaluation of this end point: Dynamic change in DNA-TGN levels every other week for the first 6 weeks, then every week during dosage escalation of 6TG to MP/MTX treatment, then every other week during the rest of trial period. The trial period is max. 64/72 weeks depending on diagnosed with Intermediate risk (IR) or Standard risk (SR) ALL, respectively . | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change in median Ery-TGN/Ery-MeMP. 6TG doses and myelo-/hepatotoxicities encountered during MTX/6MP/6TG therapy (WBC, ANC, TBC, ALAT, bilirubin, factors 2-7-10, signs of SOS, second malignancy, mortality).;Timepoint(s) of evaluation of this end point: The thiopurine metabolites (Ery-TGN and Ery-MeMP), hematology and liver parameters are measured every 2 weeks during the trial period. 6TG doses noted in the CRF and in the patient's diary. The trial period is max. 64/72 weeks depending on diagnosed with IR or SR ALL , respectively . | — |
Countries
Denmark, Finland
Contacts
Public ContactBonkolab, Rigshospitalet
Bonkolab
Outcome results
None listed