- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00548431
NOPHO ALL-2008 Pilot Study on Consolidation Therapy for Children and Adolescents With Acute Lymphoblastic Leukemia
November 19, 2016 updated by: Kjeld Schmiegelow, Rigshospitalet, Denmark
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
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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 Type
Interventional
Enrollment (Actual)
38
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
4 months to 16 years (Child, Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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
|
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 Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
3 months ( 79 days )
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
During the 3 months consolidation therapy
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Chair: Kjeld Schmiegelow, M.D., Pediatric Clinic II, RIgshospitalet, Copenhagen, DK-2100
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2007
Primary Completion (Actual)
January 1, 2009
Study Completion (Actual)
May 1, 2009
Study Registration Dates
First Submitted
October 23, 2007
First Submitted That Met QC Criteria
October 23, 2007
First Posted (Estimate)
October 24, 2007
Study Record Updates
Last Update Posted (Estimate)
January 9, 2017
Last Update Submitted That Met QC Criteria
November 19, 2016
Last Verified
November 1, 2016
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Leukemia
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Lymphoid
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Mercaptopurine
Other Study ID Numbers
- NOPHO HDM-6MP pilot study
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Yes
IPD 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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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