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Trial record 22 of 325 for:    "Acute Lymphocytic Leukemia" | "Methotrexate"

Optimizing 6-mercaptopurine Therapy in Pediatric Acute Lymphoblastic Leukemia by Using Allopurinol

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ClinicalTrials.gov Identifier: NCT03022747
Recruitment Status : Unknown
Verified January 2017 by Vastra Gotaland Region.
Recruitment status was:  Recruiting
First Posted : January 16, 2017
Last Update Posted : January 16, 2017
Sponsor:
Information provided by (Responsible Party):
Vastra Gotaland Region

Brief Summary:
The study will investigate, in children with acute lymphoblastic leukemia during maintenance treatment, if addition of allopurinol to conventional oral 6-mercaptopurine and methotrexate therapy, affects erythrocyte concentrations of 6-thioguanine and 6 methylmercaptopurine. The effect on hematological and liver toxicity parameters in blood will also be investigated as well as clinical toxicity.

Condition or disease Intervention/treatment Phase
Lymphoblastic Leukemia, Acute, Childhood Drug: Allopurinol Drug: Standard treatment Phase 2

Detailed Description:
After one month of conventional maintenance therapy (MT) children and adolescents, treated for acute lymphoblastic leukemia on Nordic protocols and with wild type thiopurine methyltransferase (TPMT) are eligible for the study. They will first receive a 12 week phase with normal MT during which time repeated sampling of 6-mercaptopurine (6MP) metabolite levels and other laboratory parameters will be performed. After 12 weeks, allopurinol at a dose of 50 mg/sqm is added (simultaneously reducing the dose of 6MP by 50%) and during the next 12 weeks patients are monitored closely for toxicity and samples for determination of metabolite levels and hematological and liver toxicity are obtained regularly. If, after 4 weeks of allopurinol treatment, the levels of 6-thioguanine are below 200 nmol/mmol hemoglobin, the dose of allopurinol will be increased to 100 mg/sqm. Allopurinol treatment is continued for 12 weeks after which the patients switch to their original maintenance therapy.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Optimizing 6-mercaptopurine Therapy in Pediatric Acute Lymphoblastic Leukemia by Using Allopurinol Clinical Study in Children 1-19 Years on Maintenance Therapy for Acute Lymphoblastic Leukemia.
Study Start Date : January 2017
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : April 2019


Arm Intervention/treatment
Active Comparator: Standard maintenance therapy
Standard maintenance therapy with 6 mercaptopurine and methotrexate
Drug: Standard treatment
Oral 6-mercaptopurine and methotrexate

Experimental: Allopurinol treatment
The second 12 week phase during which allopurinol is added to oral 6-mercaptopurine and methotrexate therapy
Drug: Allopurinol
Allopurinol is added to standard oral 6-mercaptopurine and methotrexate




Primary Outcome Measures :
  1. 6-thioguanine (6TG) levels in erythrocytes [ Time Frame: Up to week 25 ]
    The fraction of patients with 6TG levels over 200 nmol/mmol Hb at week 13 and 25 (ie after 12 weeks standard and allopurinol treatment respectively)


Secondary Outcome Measures :
  1. Mean level of 6-thioguanine [ Time Frame: Up to week 25 ]
    The mean level of 6TG at week 13 and 25

  2. Mean level of DNA-incorporated thioguanine (DNA-TGN) [ Time Frame: Up to week 25 ]
    The mean level of DNA-TGN at week 13 and 25

  3. Mean level of 6-methylmercaptopurine (6MMP) [ Time Frame: Up to week 25 ]
    The mean level of 6MMP at week 13 and 25

  4. Mean levels of platelets [ Time Frame: Up to week 25 ]
    Comparison of weighted mean of platelets in the treatment phases

  5. Mean levels of hemoglobin [ Time Frame: Up to week 25 ]
    Comparison of weighted mean of hemoglobin in the treatment phases

  6. Mean levels of absolute neutrophil count (ANC) [ Time Frame: Up to week 25 ]
    Comparison of weighted mean of ANC in the treatment phases

  7. Mean levels of white blood cells (WBC) [ Time Frame: Up to week 25 ]
    Comparison of weighted mean of WBC in the treatment phases

  8. Glutamate pyruvate transaminase (GPT) [ Time Frame: Up to week 25 ]
    Comparison of weighted means of serum GPT in the treatment phases

  9. Bilirubin [ Time Frame: Up to week 25 ]
    Comparison of weighted means of serum bilirubin in the treatment phases

  10. Hypoglycemia [ Time Frame: Up to week 25 ]
    Comparison of incidence of hypoglycemia and laboratory measures of metabolic disturbance during the treatment phases

  11. Metabolic disturbance [ Time Frame: Up to week 25 ]
    Comparison of incidence of laboratory measures of metabolic disturbance during the treatment phases

  12. Incidence of serious adverse events (SAE) [ Time Frame: Up to week 29 ]
    Comparison of the frequency of SAE in the treatment phases

  13. Cumulative dose of 6-mercaptopurine and methotrexate [ Time Frame: Up to week 29 ]
    Comparison of the cumulative dose of 6MP and methotrexate and days with treatment interruption in the two treatment arms



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Ages Eligible for Study:   6 Months to 19 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of acute lymphoblastic leukemia
  • Treatment according to Nordic Society for pediatric hematology/oncology (NOPHO) ALL2008 based protocols
  • Age 0-18y at time of initial diagnosis
  • TPMT wild type
  • Written informed consent

Exclusion Criteria:

  • Mature B cell lymphoblastic leukemia
  • t(9;22) positive acute lymphoblastic leukemia
  • Unknown TPMT status or presence of TPMT mutation (both heterozygous and homozygous)
  • Known intolerance to any of the chemotherapeutic drugs in the protocol
  • Major organ failure precluding administration of planned chemotherapy
  • Severe liver toxicity defined as persistent (≥ two weeks) elevation of either S-bilirubin > 50 μmol/l or S-GPT > 20 x Upper normal limit (UNL) or P-Prothrombin complex > 1.5.
  • Reduced kidney function defined as S-creatinine ≥ 1.5 x UNL.
  • Lactating female or female of childbearing potential not using adequate contraception.

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): NCT03022747


Contacts
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Contact: Jonas Abrahamsson, PhD, MD +46 707 695159 vobjab@gmail.com
Contact: Torben Ek, PhD, MD +46 706 169284 torben.ek@mac.com

Locations
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Finland
Dept of Pediatrics and Adolescents, Oulu University Hospital, Box 23, 90029 OYS, Finland Not yet recruiting
Oulu, Finland, 90029 OYS
Contact: Riita Niinimäki, MD, PhD    +358 8 3155832    riita.niinimaki@ppshp.fi   
Sweden
Childrens' Cancer Centre, Queen Silvias Childrens and Adolescents Hospital Recruiting
Gothenburg, Sweden, 416 85
Contact: Lene Karlsson, MD    +46 313435610    lene.karlsson@vgregion.se   
Linköping University Hospital, Dept of Pediatrics Not yet recruiting
Linköping, Sweden, 58185
Contact: Hartmut Vogt, MD, PhD    +46 101031343    hartmut.vogt@regionostergotland.se   
Sponsors and Collaborators
Vastra Gotaland Region
Investigators
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Study Chair: Jonas Abrahamsson, PhD, MD Childrens Cancer Center, Queen Silvia Children Hospital, Sahlgrenska Academy, Gothenburg, Sweden
Principal Investigator: Riita Niinimäki, PhD, MD Dept of Pediatrics and Adolescents, Oulu University Hospital, Box 23, 90029 OYS, Finland

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Responsible Party: Vastra Gotaland Region
ClinicalTrials.gov Identifier: NCT03022747     History of Changes
Other Study ID Numbers: Allopurinol Study V3.0
First Posted: January 16, 2017    Key Record Dates
Last Update Posted: January 16, 2017
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Methotrexate
Leukemia
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Mercaptopurine
Allopurinol
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Gout Suppressants
Free Radical Scavengers
Antioxidants