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

Sponsored by:	Rigshospitalet, Denmark
Information provided by:	Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:	NCT00548431

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 (5g/m.sq.)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 II

MedlinePlus related topics: Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: Mercaptopurine 6-Mercaptopurine L-Asparaginase Methotrexate Pegaspargase

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Pharmacokinetics/Dynamics Study
Official Title:	Phase II Study of Individual 6-Mercaptopurine Dose Increments in Children With Acute Lymphoblastic Leukemia Receiving High-Dose Methotrexate and PEG-Asparaginase

Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:

Reduction in leukemia burden (minimal residual disease) on treatment days 85 and/or 92 [ Time Frame: At the end of consolidation (3 months) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Incorporation of 6-thioguanine nucleotides into leukocyte DNA, degree of bone-marrow and hepatotoxicity, development of Asparaginase antibody production [ Time Frame: Within 3 months from therapy ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	75
Study Start Date:	December 2007
Estimated Study Completion Date:	December 2008
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Pilot arm: Experimental All patients receive basic 6-mercaptopurine and in addition high-dose methotrexate at 3 weeks intervals (3 in total) and PEG-asparaginase at 2 weeks intervals. Patients will receive dose increments of 6-mercaptopurine at day 14 after High-dose methotrexate if the myelotoxicity has been acceptable	Drug: 6-mercaptopurine Standard dose 25 mg/m.sq./day. Can be increased up to 75 mg/m.sq./day if the myelosuppression is acceptable (ANC>0.5 T-count >50)

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

Contacts

Contact: Kjeld Schmiegelow, M.D.	45-3545-1357	kschmiegelow@rh.dk
Contact: Thomas Frandsen	45-3545-8364	t-frandsen@dadlnet.dk

Locations

Denmark
Department of Pediatrics, Rigshospitalet	Recruiting
Copenhagen, Denmark
Contact: Kjeld Schmiegelow, M.D. 45-3545-1357 kschmiegelow@rh.dk
Department of Pediatrics, University Hospital	Recruiting
Odense, Denmark
Contact: Niels Carlsen, M.D. 45-6611-3333 niels.carlsen@OUH.regionsyddanmark.dk
Sweden
Department of Pediatrics, Drottning Sylvias Pediatric Hospital	Recruiting
Gothenburg, Sweden
Contact: Jonas Abrahamson, M.D. 46-707-69-5159 jonas.abrahamsson@vgregion.se

Sponsors and Collaborators

Rigshospitalet, Denmark

Investigators

Study Chair:

Kjeld Schmiegelow, M.D.

Pediatric Clinic II, RIgshospitalet, Copenhagen, DK-2100

More Information

Responsible Party:	Pediatric Clinic; Rigshopsitalet, Copenhagen DK-2100 ( Kjeld Schmiegelow, professor )
Study ID Numbers:	NOPHO HDM-6MP pilot study
Study First Received:	October 23, 2007
Last Updated:	December 30, 2008
ClinicalTrials.gov Identifier:	NCT00548431
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

Study placed in the following topic categories:

Asparaginase
Pegaspargase
Lymphatic Diseases
Leukemia
Leukemia, Lymphoid
Immunoproliferative Disorders

Precursor Cell Lymphoblastic Leukemia-Lymphoma
Methotrexate
6-Mercaptopurine
Lymphoproliferative Disorders
Lymphoma

Additional relevant MeSH terms:

Antimetabolites
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents

Physiological Effects of Drugs
Enzyme Inhibitors
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Therapeutic Uses
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 15, 2009