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

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ClinicalTrials.gov Identifier: NCT00548431
Recruitment Status : Completed
First Posted : October 24, 2007
Results First Posted : November 3, 2010
Last Update Posted : January 9, 2017
Sponsor:
Information provided by (Responsible Party):
Kjeld Schmiegelow, Rigshospitalet, Denmark

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Leukemia, Lymphocytic, Acute Drug: 6-mercaptopurine Phase 2

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : December 2007
Actual Primary Completion Date : January 2009
Actual Study Completion Date : May 2009

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. Toxicity of Treatment in Terms of Number of Participants With Serious Adverse Events or Adverse Events, Reported [ Time Frame: 3 months ( 79 days ) ]
    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 :
  1. Incorporation of 6-thioguanine Nucleotides (6TGN) Into Leukocyte DNA, Development of Asparaginase Antibody Production [ Time Frame: During the 3 months consolidation therapy ]
    Biweekly bloodsamples during the 3 months are analyzed for 6TGN incorporation into leucocyte DNA. In addition Methylated Mercaptopurine (MeMP) and Erythrocyte-Methotrexate level is measured


Eligibility Criteria
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Ages Eligible for Study:   1 Year to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00548431


Locations
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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
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Study Chair: Kjeld Schmiegelow, M.D. Pediatric Clinic II, RIgshospitalet, Copenhagen, DK-2100
More Information
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Responsible Party: Kjeld Schmiegelow, Professor, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT00548431    
Other Study ID Numbers: NOPHO HDM-6MP pilot study
First Posted: October 24, 2007    Key Record Dates
Results First Posted: November 3, 2010
Last Update Posted: January 9, 2017
Last Verified: November 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data published (Frandsen et al, Br J Haematol Oct 2011) Anonymised data on individual patients can be provided by study chair (kschmiegelow@rh.dk) including studyno, gender, age, thiopurine methyltransferase status, immunophenotype, white blood cell count at diagnosis, dose increments at time point 1 and 2 for dose adjustment, and dose-limiting toxicities
Keywords provided by Kjeld Schmiegelow, Rigshospitalet, Denmark:
Leukemia, Lymphocytic, Acute [C04.557.337.428.511]
6-mercaptopurine
methotrexate
asparaginase
Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Mercaptopurine
 Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors