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NCT01849276

Metformin+Cytarabine for the Treatment of Relapsed/Refractory AML

Terminated Phase 1 Results posted Last updated 31 January 2019
What this trial tests

Phase 1 trial testing metformin hydrochloride in Adult Acute Megakaryoblastic Leukemia (M7) in 2 participants. Terminated before completion.

Timeline
11 March 2015
Primary endpoint
21 January 2016
21 January 2016

Quick facts

Lead sponsorNorthwestern University
PhasePhase 1
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment2
Start date11 March 2015
Primary completion21 January 2016
Estimated completion21 January 2016
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Northwestern University

Who can join

18 and older, any sex, with Adult Acute Megakaryoblastic Leukemia (M7) or Adult Acute Minimally Differentiated Myeloid Leukemia (M0). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Evaluate Toxicity by Assessing the Adverse Events of Metformin and Cytarabine Primary · Checked daily during administration of cytarabine and at least 2x weekly following therapy until desired blood counts acheived (maximum 15 days)

To determine the maximum tolerated dose (MTD) by assessing the adverse events of metformin in combination with cytarabine in evaluating toxicity. Assessments will occur daily during cytarabine administration and at least twice weekly following treatment until blood count recovery.

Grade 1
GroupValue95% CI
Treatment (Enzyme Inhibitor and Chemotherapy)4
Grade 2
GroupValue95% CI
Treatment (Enzyme Inhibitor and Chemotherapy)6
Grade 3
GroupValue95% CI
Treatment (Enzyme Inhibitor and Chemotherapy)2
Grade 4
GroupValue95% CI
Treatment (Enzyme Inhibitor and Chemotherapy)0

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collect cover a 7 month period before the study was terminated early due to slow accrual. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment (Enzyme Inhibitor and Chemotherapy)
Serious: 2/2 (100%)
Deaths: 2/2

Serious adverse events (3 terms)

ReactionSystemTreatment (Enzyme Inhibito…
Gastric perforationGastrointestinal disorders
Other-TransminitisHepatobiliary disorders
SepsisInfections and infestations
Other adverse events (26 terms — click to expand)

ReactionSystemTreatment (Enzyme Inhibito…
AnemiaBlood and lymphatic system disorders
Febrile neutropeniaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
Elevated D-DimerBlood and lymphatic system disorders
Elevated INRBlood and lymphatic system disorders
Blurred visionEye disorders
DiarrheaGastrointestinal disorders
Lower gastrointestinal hemorrhage - HematocheziaGastrointestinal disorders
FeverGeneral disorders
Pleural infectionInfections and infestations
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Weight lossInvestigations
White blood cell decreasedInvestigations
HyperglycemiaMetabolism and nutrition disorders
HypoalbuminemiaMetabolism and nutrition disorders
HypoalbuminemaMetabolism and nutrition disorders
Chest wall painMusculoskeletal and connective tissue disorders
DysuriaRenal and urinary disorders
Urinary tract infectionRenal and urinary disorders
Symptomatic Bartholin glandReproductive system and breast disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
CoughRespiratory, thoracic and mediastinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Thromboembolic eventVascular disorders

Most-reported serious reactions: Gastric perforation, Other-Transminitis, Sepsis.

Data from ClinicalTrials.gov NCT01849276 adverse events section.

Sponsor's own description

The purpose of the study is to determine if metformin in combination with cytarabine is safe and effective. Participants in this research study have acute myeloid leukemia (AML) that has come back after initial treatment or has not gone away with initial therapy.There is evidence that metformin directly kills leukemia cells. Laboratory data have also shown that combinations of metformin with cytarabine are more efficient than each agent alone in killing leukemia cells in the laboratory.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Repurposing metformin for cancer treatment: current clinical studies.
    Chae YK, Arya A, Malecek MK, Shin DS, et al · · 2016 · cited 233× · PMID 27004404 · DOI 10.18632/oncotarget.8194
  2. Mitochondrial metabolism as a potential therapeutic target in myeloid leukaemia.
    de Beauchamp L, Himonas E, Helgason GV. · · 2022 · cited 119× · PMID 34561557 · DOI 10.1038/s41375-021-01416-w
  3. Reactive oxygen species in haematopoiesis: leukaemic cells take a walk on the wild side.
    Prieto-Bermejo R, Romo-González M, Pérez-Fernández A, Ijurko C, et al · · 2018 · cited 87× · PMID 29940987 · DOI 10.1186/s13046-018-0797-0
  4. Mitochondrial metabolism as a target for acute myeloid leukemia treatment.
    Panina SB, Pei J, Kirienko NV. · · 2021 · cited 68× · PMID 33883040 · DOI 10.1186/s40170-021-00253-w
  5. Metformin and Cancer, an Ambiguanidous Relationship.
    Skuli SJ, Alomari S, Gaitsch H, Bakayoko A, et al · · 2022 · cited 38× · PMID 35631452 · DOI 10.3390/ph15050626
  6. Metformin and blood cancers.
    Cunha Júnior AD, Pericole FV, Carvalheira JBC. · · 2018 · cited 22× · PMID 30208162 · DOI 10.6061/clinics/2018/e412s
  7. Drug Repurposing for the Treatment of Acute Myeloid Leukemia.
    Andresen V, Gjertsen BT. · · 2017 · cited 21× · PMID 29238707 · DOI 10.3389/fmed.2017.00211
  8. Repurposing Drugs for Acute Myeloid Leukemia: A Worthy Cause or a Futile Pursuit?
    Wojcicki AV, Kadapakkam M, Frymoyer A, Lacayo N, et al · · 2020 · cited 15× · PMID 32069925 · DOI 10.3390/cancers12020441

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