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

Leukemia, Lymphocytic, Acute Clinical Trial

Official title:

Phase II Study of Individual 6-mercaptopurine(6MP) Dose Increments in Children With Acute Lymphoblastic Leukemia (ALL) Receiving High-dose Methotrexate (HDM) and PEG-asparaginase

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00548431
• Other study ID #: NOPHO HDM-6MP pilot study
• Status: Completed
• Phase: Phase 2
• First received: October 23, 2007
• Last updated: June 30, 2013
• Start date: December 2007
• Est. completion date: May 2009

Study information

• Verified date: June 2013
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Dataprotection AgencyDenmark: Danish Medicines AgencyDenmark: Ethics CommitteeDenmark: The Regional Committee on Biomedical Research Ethics
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: May 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 18 Years

Eligibility

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

Study Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Acute
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• 6-mercaptopurine
Standard dose 25 mg/m^2/day. Can be increased up to 75 mg/m^2/day if the myelosuppression is acceptable (ANC>0.5 T-count >50)

Locations

Country	Name	City	State
Denmark	Department of Pediatrics, Rigshospitalet	Copenhagen
Denmark	Department of Pediatrics, University Hospital	Odense
Sweden	Department of Pediatrics, Drottning Sylvias Pediatric Hospital	Gothenburg

Sponsors (1)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark

Countries where clinical trial is conducted

Denmark,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity of Treatment in Terms of Number of Participants With Serious Adverse Events or Adverse Events, Reported	Number of participants following the protocol treatment for the full consolidation therapy with toxicity in this pilot study trying to individually titrate 6-mercaptopurine to the highest tolerable level during Consolidation.	3 months ( 79 days )	Yes
Secondary	Incorporation of 6-thioguanine Nucleotides (6TGN) Into Leukocyte DNA, Development of Asparaginase Antibody Production	Biweekly bloodsamples during the 3 months are analyzed for 6TGN incorporation into leucocyte DNA. In addition Methylated Mercaptopurin (MeMP) and Erythrocyte-Methotrexate level is measured	During the 3 months consolidation therapy	No