Metformin Reduce the Relapse Rate on Patients With B-cell Precursor (Ph+ Negative) Acute Lymphoblastic Leukemia
Effect of the Addition of Metformin Hydrochloride on the Prognosis of Patients With B-cell Precursor (Ph+ Negative) Acute Lymphoblastic Leukemia With High Expression of ABCB1 Gene
1 other identifier
interventional
102
0 countries
N/A
Brief Summary
Metformin's Antitumor activity were identified from differens diabetic patients trials, mainly associated to its mechanism of action and protein - kinase AMPK (AMP-activated protein kinase) activation. According to Cancer and Diabetes International Consensus from 2012, diabetes increases the risk for developping cancer and metformin has an protector effect against cancer cells and has an impact on overall survival. Chemotherapy drug resistance induces treatment fail in oncology. Metformin increases AMPK levels, blocks PI3K (phosphatidylinositol 3- kinase)/ AKT /mTOR(mammailian Target of Rapamycin) pathway but few evidence associated with drug resistance gene expression. This is an, experimental one-center study that pretends to stablish the effect of adding metformin 850 mg PO three times a day over the multi-drug resistance gene expression (ABCB1) in de novo Acute Lymphoblastic Leukemia in one 7-days cycle with prednisone as pre-treatment- and on the induction remission treatment.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for not_applicable
Started Jan 2015
Typical duration for not_applicable
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2016
CompletedFirst Submitted
Initial submission to the registry
April 7, 2017
CompletedFirst Posted
Study publicly available on registry
April 18, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
April 30, 2017
CompletedJuly 6, 2017
April 1, 2017
1.9 years
April 7, 2017
July 4, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Effect of Metformin on first line treatment Refractoriness in high risk failure ALL patients
Effect on the refractoriness frequency in high risk failure patients (High levels of ABCB1)
28 day induction remission treatment
Effect of Metformin on relapse rate and survival of high risk failure ALL patients
Effect of Metformin on Relapse Free Survival (RFS) on patients with high risk failure (high levels of ABCB1 gene )
12 months of follow up
Study Arms (2)
metformin
ACTIVE COMPARATORMetformin 850mg PO three times a day, during the pre-induction with steroids, induction remission, consolidation and maintenance
No metformin
NO INTERVENTIONInterventions
Metformin 850 mg PO three times a day plus prednisone in one 7-days cycle as pre-treatment and during the 28 days induction remission treatment, consolidation therapy and maintenance
Eligibility Criteria
You may qualify if:
- \> 18 years
- de novo B-cell precursor Acute Lymphoblastic Leukemia
- candidates to first line treatment protocol
- ECOG (Eastern Cooperative Oncology Group) Scale of Performance Status 1/2
- Informed Consent Form for genetic analysis samples
- Precursor B Cell Acute Lymphoblastic Leukemia
You may not qualify if:
- Diagnose of Acute Myelogenous Leukemia or Biphenotype Leukemia
- Diagnose of type 2 Diabetes Mellitus
- Previous use of Metformin
- Relapsed Acute Leukemia that require treatment protocol to be started
- Intolerance to prednisone
- ECOG Scale of Performance Status 3/4
- T-cell Acute Lymphoblastic Leukemia
- Philadelphia positive Acute Lymphoblastic Leukemia
- Tumor lysis syndrome at diagnose
- Renal Failure (creatinine leve higher than 2mg/dl)
- Several liver damage (\>2 levels de upper normal limit of Aspartate transaminase (AST) and alanine transaminase (ALT)
- Metabolic Acidosis or Lactic Acidosis at diagnose
- Central nervous system infiltration at diagnose
- Extramedullary disease (skin, pleura,eye)
- Active GI bleeding
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Related Publications (3)
Kim HG, Hien TT, Han EH, Hwang YP, Choi JH, Kang KW, Kwon KI, Kim BH, Kim SK, Song GY, Jeong TC, Jeong HG. Metformin inhibits P-glycoprotein expression via the NF-kappaB pathway and CRE transcriptional activity through AMPK activation. Br J Pharmacol. 2011 Mar;162(5):1096-108. doi: 10.1111/j.1476-5381.2010.01101.x.
PMID: 21054339BACKGROUNDOlarte Carrillo I, Ramos Penafiel C, Miranda Peralta E, Rozen Fuller E, Kassack Ipina JJ, Centeno Cruz F, Garrido Guerrero E, Collazo Jaloma J, Nacho Vargas K, Martinez Tovar A. Clinical significance of the ABCB1 and ABCG2 gene expression levels in acute lymphoblastic leukemia. Hematology. 2017 Jun;22(5):286-291. doi: 10.1080/10245332.2016.1265780. Epub 2016 Dec 14.
PMID: 27960630BACKGROUNDRamos-Penafiel C, Olarte-Carrillo I, Ceron-Maldonado R, Rozen-Fuller E, Kassack-Ipina JJ, Melendez-Mier G, Collazo-Jaloma J, Martinez-Tovar A. Effect of metformin on the survival of patients with ALL who express high levels of the ABCB1 drug resistance gene. J Transl Med. 2018 Sep 3;16(1):245. doi: 10.1186/s12967-018-1620-6.
PMID: 30176891DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER GOV
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
April 7, 2017
First Posted
April 18, 2017
Study Start
January 1, 2015
Primary Completion
December 1, 2016
Study Completion
April 30, 2017
Last Updated
July 6, 2017
Record last verified: 2017-04