Study of 6-Thioguanine in Combination With 6-Mercaptopurine During Maintenance Therapy of Childhood Lymphoma

• Status: Withdrawn
• Trial end date: 2016-10-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this phase 1-2 study is to explore the applicability of supplementing standard methotrexate/6-mercaptopurine (MTX/6MP) maintenance therapy of children with non-Hodgkin lymphoma with 6-thioguanine (6TG).

The investigators hypothesize that addition of 6TG to 6MP-based maintenance therapy of patients with high TPMT activity will mimic the more favourable thiopurine metabolism of patients with low TPMT activity and ultimately reduce relapse rates.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kjeld Schmiegelow
• Collaborators: Aalborg Universitetshospital; Aalborg University Hospital; Aarhus University Hospital Skejby; Odense University Hospital
• Treatments: 6-Mercaptopurine; Methotrexate; Thioguanine

Criteria

Inclusion Criteria:

• Confirmed histomorphological or cytomorphological diagnosis of NHL or ALL.

• Meets just one of the following:

1. Patient with NHL treated after the EURO-LB 02 protocol with at least 3.5 months of 6MP/MTX maintenance therapy remaining or

2. Patient with ALL or NHL not achieving the target WBC (patients with a WBC > 3.0 x10^9/L) and/or experience elevated liver enzymes (ALAT > UNL) attributed to a simultaneous high Ery-MeMP level on standard MTX/6MP maintenance therapy.

• TPMT wild-type genotype or TPMT high activity phenotype (TPMT activity above 14 IU/mL or during maintenance therapy TPMT above 8 IU/mL measured in erythrocytes).

• Bilirubin < 35 micromol/L, factor 2-7-10 > 0.5 or INR < 1.5 and normal hepatic blood flow (verified by ultrasound) within 1 week prior to inclusion.

• WBC > 1.5 x10^9/L, ANC > 0.5 x10^9/L and TBC > 50 x10^9/L within 1 week prior to inclusion.

• Pubertal females, Tanner stage B3/PH3 or higher, must present with a negative pregnancy test.

• Sexually active females must use accepted safe contraception (OCPs, IUD, transdermal hormonal patch, vaginal hormonal ring or subdermal hormonal implants) during therapy and until a month after completion of therapy.

• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

• Oral and written informed consent to participate have been provided by both the parents (and when appropriate by the patient) according to the ICH/GCP guidelines and the Helsinki II Declaration.

• Patients with acute lymphoblastic lymphoma (0-17.9 yrs) not achieving the target WBC (patients with a WBC > 3.0 x10^9/L) and/or experience elevated liver enzymes (ALAT > UNL) attributed to a simultaneous high Ery-MeMP level on standard MTX/6MP maintenance therapy.

Exclusion Criteria:

• Any clinical suspicion of relapse or disease progression on routine imaging or in laboratory results.

• Previous veno-occlusive disease (VOD).

• Allergy towards any of the ingredients in the three medicinal products used in the study.