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

NCT02141100 | Withdrawn Phase 1 DMC

• 1 other identifier: JMC-2014-6TG/6MP
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Non-Hodgkin Lymphoma

Keywords

thioguanine; mercaptopurine; methotrexate

Outcome Measures

Primary Outcomes (1)

• Change in median thiopurine metabolite index

  Change in Ery-TGN/Ery-MeMP after addition of 6-thioguanine to therapy. The thiopurine metabolites will be measured every 2 weeks during the trial period. The trial period is max. 12 months.

  Every 2 weeks up to the max. trial period of 12 months

Secondary Outcomes (2)

• Toxicities

  Minimum every 2 weeks, up to 12 months

• Change in median DNA-TG

  Every 2 weeks, up to 12 months

Study Arms (1)

6-thioguanine, 6-mercaptopurine and methotrexate

EXPERIMENTAL

This is the only treatment arm; all eligible patients will receive standard methotrexate/6-mercaptopurine (6MP/MTX) maintenance therapy supplemented with 6-thioguanine (6TG). Patients are enrolled when they have 12 to 3.5 months remaining of their maintenance therapy. After dose reduction in 6MP to 2/3 of the current dose 6TG therapy is initiated with a starting dose of 2.5 mg/m2/day. The 6TG dose will hereafter be increased at 2.5 mg/m2/day every 14 days until a max. of 12.5 mg/m2/day is reached or until the thiopurine metabolite profile (Ery-TGN/Ery-MeMP) has been increased by at least a factor 5.

Drug: 6-thioguanine

Interventions

6-thioguanine DRUG

All eligible patients will be supplemented with 6-thioguanine in addition to the standard therapy with 6-mercaptopurine and methotrexate. In case of significant myelo-/hepatotoxicity all therapy will be paused. If patients develop VOD they will be excluded from further 6TG therapy.

6-thioguanine, 6-mercaptopurine and methotrexate

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Confirmed histomorphological or cytomorphological diagnosis of NHL or ALL.
• Meets just one of the following:
• Patient with NHL treated after the EURO-LB 02 protocol with at least 3.5 months of 6MP/MTX maintenance therapy remaining or
• 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).
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kjeld Schmiegelow: lead
• Aalborg University Hospital: collaborator
• Aarhus University Hospital Skejby: collaborator
• Odense University Hospital: collaborator

Study Sites (1)

Dept. of Pediatric Oncology, JMC, Rigshospitalet

Copenhagen, 2100, Denmark

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

Thioguanine

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Kjeld Schmiegelow, M.D.

  Rigshospitalet, Denmark

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, DMSc

Study Record Dates

• First Submitted: May 7, 2014
• First Posted: May 19, 2014
• Study Start: July 1, 2014
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: October 7, 2016

Record last verified: 2016-10

Locations

DK (1)