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

This study has been completed.
Sponsor:
Information provided by:
Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT00548431
First received: October 23, 2007
Last updated: November 9, 2010
Last verified: November 2010
History of Changes
  Purpose

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.


Condition Intervention Phase
Leukemia, Lymphocytic, Acute
 Drug: 6-mercaptopurine
 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • Toxicity of Treatment in Terms of Number of Participants With Serious Adverse Events or Adverse Events, Reported [ Time Frame: 3 months ( 79 days ) ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Incorporation of 6-thioguanine Nucleotides (6TGN) Into Leukocyte DNA, Development of Asparaginase Antibody Production [ Time Frame: During the 3 months consolidation therapy ] [ Designated as safety issue: No ]
    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


Enrollment: 38
Study Start Date: December 2007
Study Completion Date: May 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 6 mercaptopurine arm
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
 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)
Other Name: PURINETHOL

Detailed 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.

  Eligibility

Ages Eligible for Study:   1 Year to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00548431

Locations
Denmark
Department of Pediatrics, Rigshospitalet
Copenhagen, Denmark
Department of Pediatrics, University Hospital
Odense, Denmark
Sweden
Department of Pediatrics, Drottning Sylvias Pediatric Hospital
Gothenburg, Sweden
Sponsors and Collaborators
Rigshospitalet, Denmark
Investigators
Study Chair: Kjeld Schmiegelow, M.D. Pediatric Clinic II, RIgshospitalet, Copenhagen, DK-2100
  More Information

No publications provided

Responsible Party: Kjeld Schmiegelow, professor, Pediatric Clinic; Rigshopsitalet, Copenhagen DK-2100
ClinicalTrials.gov Identifier: NCT00548431     History of Changes
Other Study ID Numbers: NOPHO HDM-6MP pilot study
Study First Received: October 23, 2007
Results First Received: June 24, 2009
Last Updated: November 9, 2010
Health Authority: Denmark: Danish Dataprotection Agency
Denmark: Danish Medicines Agency
Denmark: Ethics Committee
Denmark: The Regional Committee on Biomedical Research Ethics

Keywords provided by Rigshospitalet, Denmark:
Leukemia, Lymphocytic, Acute [C04.557.337.428.511]
6-mercaptopurine
methotrexate
asparaginase

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
6-Mercaptopurine
Methotrexate
Pegaspargase
Asparaginase
Antimetabolites
Molecular Mechanisms of Pharmacological Action
 Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Dermatologic Agents
Folic Acid Antagonists
Antirheumatic Agents

ClinicalTrials.gov processed this record on May 23, 2013