Prevention of Methotrexate Induced Nephrotoxicity and Prolonged Drug Elimination Time With 12 Hours Prehydration

NCT00570817 | Completed DMC

• 3 other identifiers: 20070009The Danish DataProtection Agency 2007-41-0014
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

Infusions with high-dose methotrexate 5 g/m2 or 8 g/m2 are used to treat children with acute lymphoblastic leukemia (ALL), non-Hodgkin's lymphoma, medulloblastoma and ependymoma. Methotrexate is primarily excreted unchanged by the kidney where it can course acute kidney damage resulting in prolonged time of excretion of the drug. Our main hypothesis is that 12 hours of intravenous hydration before the methotrexate infusion is more efficacious in preventing methotrexate induced kidney damage compared to four hours of hydration.

Conditions

Methotrexate Induced Nephrotoxicity

Keywords

Methotrexate; Nephrotoxicity; Hydration; Acute lymphoblastic leukemia; Non-Hodgkin's lymphoma; Medulloblastoma; Ependymoma; Prolonged elimination time of methotrexate

Outcome Measures

Primary Outcomes (1)

• Prolonged methotrexate elimination time, defined by serum methotrexate concentrations: > 3,0 micromol/L at 36 hours; > 1,0 micromol/L at 42 hours or > 0,2 micromol/L at 66 hours after initiation of the methotrexate infusion.

  From 36-66 hours after the initiation of methotrexate infusion.

Secondary Outcomes (6)

• Development of methotrexate induced nephropathy, defined by an increase in serum creatinine by 50% or more compared with the serum creatinine concentration before start of each methotrexate infusion.

  From the initiation of methotrexate infusion until 66 hours after.

• Days of hospitalization in relation to the methotrexate infusion.

  Days in relation to the methotrexate infusion and side effects.

• Difference in baseline creatinine to highest serum creatinine between groups.

  From initiation of the methotrexate infusion and up til 14 days after.

• Drug exposure measured by area under the curve.

  From 23 hours til 66 hours after initiation of the methotrexate infusion.

• Duration and degree of side effects to the methotrexate treatment.

  From initiation of the methotrexate infusion and up til on month after.

Study Arms (2)

1

OTHER

The child will receive prehydration at the methotrexate infusions in the following order: At the 1st methotrexate infusion the child will receive 4 hours prehydration. At the 2nd methotrexate infusion the child will receive 12 hours prehydration. At the 3rd methotrexate infusion the child will receive 4 hours prehydration. At the 4th methotrexate infusion the child will receive 12 hours prehydration. At the 5th methotrexate infusion the child will receive 4 hours prehydration. At the 6th methotrexate infusion the child will receive 12 hours prehydration. At the 7th methotrexate infusion the child will receive 4 hours prehydration. At the 8th methotrexate infusion the child will receive 12 hours prehydration.

Other: 12 hours of prehydration

2

OTHER

The child will receive prehydration at the methotrexate infusions in the following order: At the 1st methotrexate infusion the child will receive 12 hours prehydration. At the 2nd methotrexate infusion the child will receive 4 hours prehydration. At the 3rd methotrexate infusion the child will receive 12 hours prehydration. At the 4th methotrexate infusion the child will receive 4 hours prehydration. At the 5th methotrexate infusion the child will receive 12 hours prehydration. At the 6th methotrexate infusion the child will receive 4 hours prehydration. At the 7th methotrexate infusion the child will receive 12 hours prehydration. At the 8th methotrexate infusion the child will receive 4 hours prehydration.

Other: 12 hours of prehydration

Interventions

12 hours of prehydration OTHER

12 hours of prehydration with an infusion rate of 150 ml/m2/hour with a solution of 5% glucose with 40 mmol sodium bicarbonate/L and 20 mmol potassium chloride/L.

1; 2

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age between 1 and 21 years at the diagnosis of ALL
• Treatment with high-dose methotrexate 5 g/m2 or 8 g/m2 according to the protocol "Nordic Association for Pediatric Hematology and Oncology 2000 (NOPHO-2000)" or the new protocol (NOPHO-2008) to which enrolment begin approx. January 2009.
• Treatment with high-dose methotrexate 5 g/m2 according to the protocol "Treatment Protocol for T-Cell and B-Precursor Cell Lymphoblastic Lymphoma 2002 of the European Inter-group Co-operation on Childhood Non-Hodgkin-Lymphoma (EICNHL)"
• Treatment of medulloblastoma and ependymoma with high-dose methotrexate 5 g/m2 according to the protocol: "(HIT2000)Hirntumorprotokoll der Hrbeitsgruppe für Hirntumoren" from Deutsche Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH).

You may not qualify if:

• Patient or parents not willing to give consent.

Sponsors & Collaborators

• University of Aarhus: lead
• ML Jørgensen og Gunnar Hansens Foundation: collaborator
• Danish Child Cancer Foundation: collaborator

Study Sites (1)

Aarhus University Hospital, Skejby

Aarhus, Aarhus N, 8200, Denmark

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin; Medulloblastoma; Ependymoma

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Henrik Schrøder, MD

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2007
• First Posted: December 11, 2007
• Study Start: June 1, 2007
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: November 7, 2011

Record last verified: 2011-01

Locations

DK (1)