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Effect of Metformin on ABCB1 and AMPK Expression in Adolescents With Newly Diagnosed Acute Lymphoblastic Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05326984
Recruitment Status : Recruiting
First Posted : April 14, 2022
Last Update Posted : April 14, 2022
Sponsor:
Information provided by (Responsible Party):
Daniel Ortiz Morales, Hospital General de Mexico

Brief Summary:

Acute lymphoblastic leukemia, is the most frequent cancer in children and adolescents. Some genes have been described to produce drug resistance, as ABCB1 probably by lack of activation of AMPK. Some manuscripts have shown that metformin has antitumoral activity, mainly by activation of AMPK.

This is an experimental one center trial, that pretend analyze the effect of metformin at a dose of 1000mgm2 per day, on the expression of the ABCB1 and AMPK genes, when is added to conventional induction remission chemotherapy in newly diagnosed adolescents with acute lymphoblastic leukemia.


Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Drug: Metformin Not Applicable

Show Show detailed description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The patients are randomized assigned to one of two groups. One group (control group) will receive conventional chemotherapy during remission induction, the other group will receive conventional chemotherapy plus metformin 1000mgm2 per day during the remission induction.
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Effect of Metformin on ABCB1 and AMPK Expression in Adolescents With Newly Diagnosed Acute Lymphoblastic Leukemia
Actual Study Start Date : February 9, 2021
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2023


Arm Intervention/treatment
No Intervention: Control group
This subjets will receive conventional chemotherapy alone. The Remission induction chemotherapy includes a steroid pre-phase of 7 days of prednisone 60mgm2SCD. The proper remission induction phase consist in prednisone 60mgm2 daily from day 0 to 28; Vincristine 1.5mgm2 on days 0, 7, 14 and 21; Doxorubicin 25mgm2 on days 0, 7, 21; L-asparaginase 10, 000 Um2 on days 2, 4, 6, 8, 10 and 12. Etoposide 300mgm2 and cytarabine 300mgm2 on days 22, 25 and 29. Intrathecal chemotherapy is administered on days 0, 7, 14 and 21.
Experimental: Interventional group

This group will receive conventional chemotherapy plus metformin 1000mgm2 per day, with maximum dose of 850mg three times a day, from day -7 to the end of the remission induction period.

The Remission induction chemotherapy includes a steroid pre-phase of 7 days of prednisone 60mgm2SCD. The proper remission induction phase consist in prednisone 60mgm2 daily from day 0 to 28; Vincristine 1.5mgm2 on days 0, 7, 14 and 21; Doxorubicin 25mgm2 on days 0, 7, 21; L-asparaginase 10, 000 Um2 on days 2, 4, 6, 8, 10 and 12. Etoposide 300mgm2 and cytarabine 300mgm2 on days 22, 25 and 29. Intrathecal chemotherapy is administered on days 0, 7, 14 and 21.

Drug: Metformin
Metformin will be administered orally to the experimental group by randomization at a dose of 1000mgm2 per day, with maximum dose of 850mg three times a day, from day -7 to the end of the remission induction period.




Primary Outcome Measures :
  1. Decrease of ABCB1 gene expression [ Time Frame: The assessment of ABCB1 gene expression will be made at diagnosis (day -7) and at the end of remission induction phase on day +33 ]
    During the trial ABCB1 gene expression is measure by rt-PCR in mononuclear cells in peripheral blood, at at the beginning of treatment and end of the remission induction

  2. Increase of AMPK gene expression [ Time Frame: The assessment of AMPK gene expression will be made at diagnosis (day -7) and at the end of remission induction phase on day +33 ]
    During the trial AMPK gene expression is measure by rt-PCR in mononuclear cells in peripheral blood, at athe beginning and end of the remission induction.


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: From randomization and initiation of the treatment until the date of death from any cause, assessed up to 2 years ]
    The probability of being alive after the randomization of the subjects. Is going to be measure by Kaplan Meir method, and compare between the expression of ABCB1 and AMPK genes, and the use of metformin with the log rank statistics.

  2. Event free survival [ Time Frame: From randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed upt to 2 years ]
    The probability of being alive without relapse after randomization of the participants. Will be assess by Kaplan Meir statistics, and compare with log rank.



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Ages Eligible for Study:   10 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Newly diagnosed adolescents with acute lymphoblastic leukemia by morphology analysis in bine marrow
  • Adolescents between 10 and 21 years old
  • Participants with the informed consent signed by themselves and the parents or legally authorized representative.

Exclusion Criteria:

  • Participants with previous use of any antineoplastic drug
  • Down syndrome patients

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): NCT05326984


Contacts
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Contact: Daniel Ortiz Morales, MSc +52 552789200 ext 2037 dr.ortiz_morales@outlook.com
Contact: Adolfo Martinez Tovar, PhD +52 552789200 ext 1162 mtadolfo73@hotmail.com

Locations
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Mexico
Hospital General de México Recruiting
Mexico City, Mexico, 06720
Contact: Daniel Ortiz Morales, MSc    +525527892000 ext 2037    dr.ortiz_morales@outlook.com   
Contact: Adolfo Martinez Tovar, PhD    +525527892000 ext 1162    mtadolfo73@hotmail.com   
Sponsors and Collaborators
Hospital General de Mexico
Investigators
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Study Chair: Adolfo Martinez Tovar, PhD Hospital General de méxico
  Study Documents (Full-Text)

Documents provided by Daniel Ortiz Morales, Hospital General de Mexico:
Informed Consent Form  [PDF] February 20, 2020

Publications:

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Responsible Party: Daniel Ortiz Morales, Head of pediatric hematology & oncology, Hospital General de Mexico
ClinicalTrials.gov Identifier: NCT05326984    
Other Study ID Numbers: DI/21/505/03/10
First Posted: April 14, 2022    Key Record Dates
Last Update Posted: April 14, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: The data is going to be coded, and the relation between data and code are only known by the researches and the IRB (institutional review board).

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Daniel Ortiz Morales, Hospital General de Mexico:
adolescents
metformin
ABCB1
AMPK
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
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs