Effect of Metformin on ABCB1 and AMPK Expression in Adolescents With Newly Diagnosed Acute Lymphoblastic Leukemia
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| ClinicalTrials.gov Identifier: NCT05326984 |
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Recruitment Status :
Recruiting
First Posted : April 14, 2022
Last Update Posted : April 14, 2022
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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 detailed description
| 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 |
|---|---|
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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.
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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. |
- 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
- 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.
- 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.
- 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 |
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
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
| 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 |
| 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 | |
| Study Chair: | Adolfo Martinez Tovar, PhD | Hospital General de méxico |
Documents provided by Daniel Ortiz Morales, Hospital General de Mexico:
| 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). |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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adolescents metformin ABCB1 AMPK |
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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 |