NOPHO ALL-2008 Pilot Study on Consolidation Therapy for Children and Adolescents With Acute Lymphoblastic Leukemia

Rigshospitalet

Status and phase: Completed; Phase 2

Conditions: Leukemia, Lymphocytic, Acute

Treatments: Drug: 6-mercaptopurine

Study type: Interventional

Funder types: Other

Identifiers

NCT00548431

NOPHO HDM-6MP pilot study

Details and patient eligibility

About

The present pharmacokinetic (PK)-pharmacodynamic (PD) study will explore the toxicity and antileukemic response during the initial 3 months of individualised therapy of children and young adults with acute lymphoblastic leukemia (ALL). The investigators will on an individual toxicity-titrated basis attempt to increase the dose intensity of the 6-mercaptopurine used in the two-months post-remission treatment phase of lower risk childhood ALL. This will be performed together with continuous PEG-ASP (every 2nd week) and interspersed HD-MTX (5 g/m^2) every 3rd week. Thus, the trial will also test the feasibility of this particular drug combination.

Full description

In addition to the details above we will also explore

• the relationship of the post-HD-MTX MRD-levels with the dose of 6MP, TPMT-activity, DNA-6TGN, E-6TGN, E-MeMP, E-MTX, and presence of ASP-antibodies,
• the early development of anti-ASP antibodies during continuous PEG-ASP therapy.

The study could improve the understanding of the pharmacodynamics of the 6MP/HD-MTX interaction in combination with PEG-ASP.

Enrollment: 38 patients

Sex: All

Ages: 1 to 18 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• B-lineage ALL
• 1-17.9 years
• WBC <100, clinical remission obtained day 2
• Written consent to participation.

Exclusion criteria

• t(9;22)
• Hypodiploidy
• 11q23-aberrations
• TPMT-deficiency
• Intolerance to MTX or 6MP

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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38 participants in 1 patient group

6 mercaptopurine arm

Experimental group

Description:

All patients received basic daily 6MP (6-mercaptopurine) (25 mg/m\^2) and in addition high-dose methotrexate(HDM) every 3rd week (3 times HDM in total) and PEG-asparaginase every 14th day. Patients increased the dose of 6MP 2 weeks after each HDM if if the myelotoxicity had been acceptable. This means 2 increments since the study stopped 2 weeks after the last HDM

Treatment:

Drug: 6-mercaptopurine