Compounds > lactic acid
Page last updated: 2024-10-17

lactic acid and Lymphoma, Large B-Cell, Diffuse

lactic acid has been researched along with Lymphoma, Large B-Cell, Diffuse in 10 studies

Lactic Acid: A normal intermediate in the fermentation (oxidation, metabolism) of sugar. The concentrated form is used internally to prevent gastrointestinal fermentation. (From Stedman, 26th ed)
2-hydroxypropanoic acid : A 2-hydroxy monocarboxylic acid that is propanoic acid in which one of the alpha-hydrogens is replaced by a hydroxy group.

Lymphoma, Large B-Cell, Diffuse: Malignant lymphoma composed of large B lymphoid cells whose nuclear size can exceed normal macrophage nuclei, or more than twice the size of a normal lymphocyte. The pattern is predominantly diffuse. Most of these lymphomas represent the malignant counterpart of B-lymphocytes at midstage in the process of differentiation.

Research Excerpts

ExcerptRelevanceReference
"Type B lactic acidosis is a rare complication of non-tissue perfusion abnormalities caused by solid tumors or hematologic malignancies."8.12Type B lactic acidosis associated with diffuse large B-cell lymphoma and the Warburg effect. ( Lv, Z; Wang, C; Zhang, Y, 2022)
" We describe a rare case of multiple organ failure due to intravascular lymphoma with severe lactic acidosis in a patient who survived."7.96Successful Intensive Care Treatment of Severe Lactic Acidosis and Tumor Lysis Syndrome Related to Intravascular Lymphoma. ( Genda, Y; Ichiba, S; Mase, H; Ogawa, Y; Sakamoto, A; Takeuchi, J, 2020)
" We examined the monocarboxylate transporter 1 inhibitor AZD3965, currently in phase I clinical studies, as a potential therapy for diffuse large B-cell lymphoma and Burkitt lymphoma."7.85Inhibition of monocarboxyate transporter 1 by AZD3965 as a novel therapeutic approach for diffuse large B-cell lymphoma and Burkitt lymphoma. ( Bacon, CM; Bell, N; Blair, H; Bomken, S; Critchlow, SE; Crossland, R; Keun, HC; Long, A; Miwa, S; Nakjang, S; Noble, RA; Phillips, N; Rand, V; Sikka, A; Televantou, D; Thomas, H; Wedge, SR, 2017)
"We report a 76-year-old Caucasian woman with double-expressor diffuse large B cell lymphoma who presented with severe lactic acidosis and extreme hypoglycemia with normal mentation."4.31Clinical presentation of Warburg effect in aggressive lymphoma: a case report. ( Afzal, MZ; Cao, Y; Chen, Y; Hanlon, EL; Hayes, CA; Hill, JM; Liu, MC, 2023)
"Type B lactic acidosis is a rare complication of non-tissue perfusion abnormalities caused by solid tumors or hematologic malignancies."4.12Type B lactic acidosis associated with diffuse large B-cell lymphoma and the Warburg effect. ( Lv, Z; Wang, C; Zhang, Y, 2022)
" We describe a rare case of multiple organ failure due to intravascular lymphoma with severe lactic acidosis in a patient who survived."3.96Successful Intensive Care Treatment of Severe Lactic Acidosis and Tumor Lysis Syndrome Related to Intravascular Lymphoma. ( Genda, Y; Ichiba, S; Mase, H; Ogawa, Y; Sakamoto, A; Takeuchi, J, 2020)
" We examined the monocarboxylate transporter 1 inhibitor AZD3965, currently in phase I clinical studies, as a potential therapy for diffuse large B-cell lymphoma and Burkitt lymphoma."3.85Inhibition of monocarboxyate transporter 1 by AZD3965 as a novel therapeutic approach for diffuse large B-cell lymphoma and Burkitt lymphoma. ( Bacon, CM; Bell, N; Blair, H; Bomken, S; Critchlow, SE; Crossland, R; Keun, HC; Long, A; Miwa, S; Nakjang, S; Noble, RA; Phillips, N; Rand, V; Sikka, A; Televantou, D; Thomas, H; Wedge, SR, 2017)
" Using xenografts of the most common form of human NHL, diffuse large B-cell lymphoma (DLBCL), we have detected therapeutic response within one cycle of therapy with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), rituximab plus CHOP (RCHOP) or radiation (15 Gy) through detection of a decrease in lactic acid (Lac) or total choline (tCho) and an increase of apparent diffusion coefficients (ADC)."3.77NMR metabolic and physiological markers of therapeutic response. ( Delikatny, EJ; Glickson, JD; Goldstein, SC; Lee, SC; Loevner, LA; Mellon, EA; Nasta, SD; Nelson, DS; Pickup, S; Poptani, H; Reddy, R; Schuster, SJ; Svoboda, J; Wallace, SG, 2011)

Research

Studies (10)

TimeframeStudies, this research(%)All Research%
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's2 (20.00)29.6817
2010's4 (40.00)24.3611
2020's4 (40.00)2.80

Authors

AuthorsStudies
Wang, C1
Lv, Z1
Zhang, Y1
Cao, Y1
Liu, MC1
Hanlon, EL1
Chen, Y1
Afzal, MZ1
Hayes, CA1
Hill, JM1
Wang, J1
Wang, Y1
Wan, L1
Chen, X1
Zhang, H1
Yang, S1
Zhong, L1
Noble, RA1
Bell, N1
Blair, H1
Sikka, A1
Thomas, H1
Phillips, N1
Nakjang, S1
Miwa, S1
Crossland, R1
Rand, V1
Televantou, D1
Long, A1
Keun, HC1
Bacon, CM1
Bomken, S1
Critchlow, SE1
Wedge, SR1
Short, JH1
Sen, A1
Mase, H1
Ogawa, Y1
Takeuchi, J1
Genda, Y1
Ichiba, S1
Sakamoto, A1
Soleja, M1
Mims, M1
Rivero, G1
Pickup, S3
Lee, SC3
Mancuso, A1
Glickson, JD3
Poptani, H2
Delikatny, EJ2
Nelson, DS2
Schuster, SJ1
Nasta, SD1
Svoboda, J1
Goldstein, SC1
Wallace, SG1
Loevner, LA1
Mellon, EA1
Reddy, R1
Huang, MQ1
Wehrli, S1
Adegbola, O1

Clinical Trials (1)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Cancer Research UK Phase I Trial of AZD3965, a Monocarboxylate Transporter 1 Inhibitor (MCT1) in Patients With Advanced Cancer[NCT01791595]Phase 153 participants (Actual)Interventional2013-04-23Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

AUC From 0 to 12 Hours Post AZD3965 Dosing

Plasma samples were analysed to determine the concentrations of AZD3965 using a previously developed LC-MS/MS method. AUC from 0 to 12 hours was applicable to twice daily dosing on Day 1 only. See AUC From 0 to 24 Hours Post AZD3965 Dosing for AUC for other cohorts and timepoints. (NCT01791595)
Timeframe: Part 1 (Cohorts 5-6): Day 1 (pre-dose; 0.25, 0.5, 1, 2, 4, 6, 12 hours post-dose)

Interventionh*ng/mL (Mean)
AZD3965 Cohort 5 (15 mg BD)1251.5
AZD3965 Cohort 6 (10 mg BD)620

Elimination Half Life for AZD3965

Plasma samples were analysed to determine the concentrations of AZD3965 using a previously developed LC-MS/MS method. (NCT01791595)
Timeframe: Part 1 (Cohorts 1-6): Day -7 (pre-dose; 0.25, 0.5, 1, 2, 4, 6, 24, 48 hours post-dose and Day 1 pre-dose (168 hours post Day -7 dose)

InterventionHour (Mean)
AZD3965 Cohort 1 (5 mg OD)51.9
AZD3965 Cohort 2 (10 mg OD)45.4
AZD3965 Cohort 3 (20 mg OD)38.3
AZD3965 Cohort 4 (30 mg OD)38.7
AZD3965 Cohort 5 (15 mg BD)37.5
AZD3965 Cohort 6 (10 mg BD)33.6

MTD of AZD3965

MTD was determined by testing increasing AZD3965 doses in Part 1 dose escalation cohorts (Cohorts 1-6) and defined as the total daily dose level below that at which ≥2 out of ≤6 evaluable patients had a dose-limiting toxicity (DLT) during Cycle 1 (including Day -7). DLTs were defined as highly probably/probably AZD3965 related haematological, cardiac, ophthalmic, other Grade 3/4 toxicity, death or drug-related toxicity causing AZD3965 interruption >2 weeks (see protocol for specific criteria) (NCT01791595)
Timeframe: Day -7 to Day 28

Interventionmg (twice daily) (Number)
Part 1 Dose Escalation (Cohorts 1-6)10

Number of Patients Who Experienced DLTs

Number of patients who experienced protocol-defined DLTs (defined according to NCI CTCAE version 4.02). DLTs were defined as highly probably/probably AZD3965 related haematological, cardiac, ophthalmic, other Grade 3/4 toxicity, death or drug-related toxicity causing AZD3965 interruption >2 weeks (see protocol for specific criteria) (NCT01791595)
Timeframe: Day -7 to Day 28

InterventionParticipants (Count of Participants)
AZD3965 Cohort 1 (5 mg OD)0
AZD3965 Cohort 2 (10 mg OD)0
AZD3965 Cohort 3 (20 mg OD)1
AZD3965 Cohort 4 (30 mg OD)1
AZD3965 Cohort 5 (15 mg BD)3
AZD3965 Cohort 6 (10 mg BD)2
AZD3965 Expansion Cohort (10 mg BD)1

Number of Patients Who Experienced Non-Serious AEs

A non-serious AE is any untoward medical occurrence that does not meet the serious criteria described for outcome measure 3 above. Specific AE terms are provided in the Adverse Events section (NCT01791595)
Timeframe: From the date of written informed consent and until 28 days after the last dose of AZD3965; an average (median) of 80 days (range: 36 to 517 days)

InterventionParticipants (Count of Participants)
AZD3965 Cohort 1 (5 mg OD)3
AZD3965 Cohort 2 (10 mg OD)5
AZD3965 Cohort 3 (20 mg OD)7
AZD3965 Cohort 4 (30 mg OD)5
AZD3965 Cohort 5 (15 mg BD)11
AZD3965 Cohort 6 (10 mg BD)7
AZD3965 Expansion Cohort (10 mg BD)11

Number of Patients Who Experienced Serious AEs

A serious adverse event (SAE) is any AE, regardless of dose, causality or expectedness, that results in death, is life-threatening, requires in-patient hospitalisation or prolongs existing in-patient hospitalisation, results in persistent or significant incapacity or disability, is a congenital anomaly or birth defect or is any other medically important event. Any ophthalmic and/or cardiac DLT is considered a medically important event and therefore an SAE in this trial. Specific AE terms are provided in the Adverse Events section (NCT01791595)
Timeframe: From the date of written informed consent and until 28 days after the last dose of AZD3965; an average (median) of 80 days (range: 36 to 517 days)

InterventionParticipants (Count of Participants)
AZD3965 Cohort 1 (5 mg OD)1
AZD3965 Cohort 2 (10 mg OD)1
AZD3965 Cohort 3 (20 mg OD)3
AZD3965 Cohort 4 (30 mg OD)2
AZD3965 Cohort 5 (15 mg BD)8
AZD3965 Cohort 6 (10 mg BD)4
AZD3965 Expansion Cohort (10 mg BD)8

Area Under the Concentration-Time Curve (AUC) From 0 to 24 Hours Post AZD3965 Dosing

Plasma samples were analysed to determine the concentrations of AZD3965 using a previously developed liquid chromatography tandem mass spectrometry (LC-MS/MS) method. For twice daily dosing, Day -7 data reflect the full daily dose but subsequent timepoints reflect half the daily dose as PK sampling was conducted up to 12 hours following the first of the two daily doses; therefore, AUC is from 0 to 12 hours at those timepoints and is reported as a separate outcome measure. (NCT01791595)
Timeframe: Part 1 (Cohorts 1-4): Day -7 (pre-dose; 0.25, 0.5, 1, 2, 4, 6, 24, 48 hours post-dose) and Day 1 (pre-dose; 0.25, 0.5, 1, 2, 4, 6, 24 hours post-dose)

,,,,,
Interventionh*ng/mL (Mean)
Day -7Day 1
AZD3965 Cohort 1 (5 mg OD)211.7274
AZD3965 Cohort 2 (10 mg OD)730.8999
AZD3965 Cohort 3 (20 mg OD)1509.32123.5
AZD3965 Cohort 4 (30 mg OD)28433031
AZD3965 Cohort 5 (15 mg BD)3984.7NA
AZD3965 Cohort 6 (10 mg BD)1540NA

Maximum Observed Plasma Concentration of AZD3965

Plasma samples were analysed to determine the concentrations of AZD3965 using a previously developed LC-MS/MS method. For twice daily dosing, Day -7 data reflect the full daily dose and other timepoints reflect half the daily dose. (NCT01791595)
Timeframe: Part 1 (Cohorts 1-6): Day -7 (pre-dose; 0.25, 0.5, 1, 2, 4, 6, 24, 48 hours post-dose), Day 1 & 29 (each pre-dose; 0.25, 0.5, 1, 2, 4, 6, 24 hours post-dose [12 hours post-dose if BD]); Part 2 (Expansion): Day 1 (pre-dose; 4, 6, 12 hours post-dose)

Interventionng/mL (Mean)
Day 1
AZD3965 Expansion Cohort (10 mg BD)78.5

Maximum Observed Plasma Concentration of AZD3965

Plasma samples were analysed to determine the concentrations of AZD3965 using a previously developed LC-MS/MS method. For twice daily dosing, Day -7 data reflect the full daily dose and other timepoints reflect half the daily dose. (NCT01791595)
Timeframe: Part 1 (Cohorts 1-6): Day -7 (pre-dose; 0.25, 0.5, 1, 2, 4, 6, 24, 48 hours post-dose), Day 1 & 29 (each pre-dose; 0.25, 0.5, 1, 2, 4, 6, 24 hours post-dose [12 hours post-dose if BD]); Part 2 (Expansion): Day 1 (pre-dose; 4, 6, 12 hours post-dose)

Interventionng/mL (Mean)
Day -7Day 1
AZD3965 Cohort 5 (15 mg BD)483.9213.6

Maximum Observed Plasma Concentration of AZD3965

Plasma samples were analysed to determine the concentrations of AZD3965 using a previously developed LC-MS/MS method. For twice daily dosing, Day -7 data reflect the full daily dose and other timepoints reflect half the daily dose. (NCT01791595)
Timeframe: Part 1 (Cohorts 1-6): Day -7 (pre-dose; 0.25, 0.5, 1, 2, 4, 6, 24, 48 hours post-dose), Day 1 & 29 (each pre-dose; 0.25, 0.5, 1, 2, 4, 6, 24 hours post-dose [12 hours post-dose if BD]); Part 2 (Expansion): Day 1 (pre-dose; 4, 6, 12 hours post-dose)

,,,,
Interventionng/mL (Mean)
Day -7Day 1Day 29
AZD3965 Cohort 1 (5 mg OD)43.438.448.6
AZD3965 Cohort 2 (10 mg OD)122135.0271.6
AZD3965 Cohort 3 (20 mg OD)222.7219.9310.1
AZD3965 Cohort 4 (30 mg OD)377.6458.4239.2
AZD3965 Cohort 6 (10 mg BD)226106.2132.3

Number of Patients Who Experienced a Complete Response, Partial Response or Stable Disease According to RECIST 1.1 or a Complete Remission, Partial Remission or Stable Disease According to the IWG Criteria for Lymphoma (Part 2 Only)

Antitumour activity measured according to RECIST version 1.1 (solid tumours)(see Eishenhauer et al; Eur J Cancer 2009, 45:228-247) or IWG criteria for Lymphoma (lymphoma)(see Cheson, Fisher et al; JCO 2014, 32:3059-3067). Complete or partial response/remission was confirmed by repeat measurements ≥4 weeks after response criteria were met; patients with stable disease met criteria at least once ≥6 weeks after first dose of AZD3965 (NCT01791595)
Timeframe: Radiological disease assessment at screening/baseline and every 6 weeks to end of treatment; an average (median) of 44 days (range: 36 to 432 days)

InterventionParticipants (Count of Participants)
Stable diseaseComplete remission
AZD3965 Expansion Cohort (10 mg BD)11

Plasma Level of Cell Death Marker M30 (Caspase-Cleaved CK18; Part 1 Only)

Plasma samples were analysed to determine the level of M30 using a validated cell death ELISA in Part 1 (Cohorts 1-6). Assays not conducted for Part 2 of the trial as considered uninformative. (NCT01791595)
Timeframe: Baseline (Day -14 to -8), Day -7 (pre-dose) Day 1 (24 hours post-dose), Day 8 (pre-dose), Day 29 (pre-dose)

,,,,,
InterventionU/L (Mean)
BaselineDay -7Day 1Day 8Day 29
AZD3965 Cohort 1 (5 mg OD)383201174.5226176
AZD3965 Cohort 2 (10 mg OD)944.8865.6860.6959.4836.7
AZD3965 Cohort 3 (20 mg OD)392.3410.1428.4457.1428
AZD3965 Cohort 4 (30 mg OD)196.0225.6220.6206.8267.8
AZD3965 Cohort 5 (15 mg BD)464.9464.8487.9418.6660.3
AZD3965 Cohort 6 (10 mg BD)359.6342336.6343.4344.6

Plasma Level of Cell Death Marker M65 (Total Plus Caspase-Cleaved CK18; Part 1 Only)

Plasma samples were analysed to determine the level of M65 using a validated cell death enzyme-linked immunosorbent assay (ELISA) in Part 1 (Cohorts 1-6). Assays not conducted for Part 2 of the trial as considered uninformative. (NCT01791595)
Timeframe: Baseline (Day -14 to -8), Day -7 (pre-dose) Day 1 (24 hours post-dose), Day 8 (pre-dose), Day 29 (pre-dose)

,,,,,
InterventionU/L (Mean)
BaselineDay -7Day 1Day 8Day 29
AZD3965 Cohort 1 (5 mg OD)533.0623.5469.0841.3801.5
AZD3965 Cohort 2 (10 mg OD)4496.03846.43935.64478.45000.0
AZD3965 Cohort 3 (20 mg OD)1602.11796.41742.01807.01226.8
AZD3965 Cohort 4 (30 mg OD)1046.6935.6981.0474.2443.0
AZD3965 Cohort 5 (15 mg BD)1344.31488.71673.01418.42609.3
AZD3965 Cohort 6 (10 mg BD)287.6233.2255.4252.0285.0

Plasma Level of Nucleosomal DNA (nDNA) as a Measure of Apoptosis (Part 1 Only)

Plasma samples were analysed to determine the level of nDNA using validated methodology in Part 1 (Cohorts 1-6). Assays not conducted for Part 2 of the trial as considered uninformative. (NCT01791595)
Timeframe: Baseline (Day -14 to -8), Day -7 (pre-dose) Day 1 (24 hours post-dose), Day 8 (pre-dose), Day 29 (pre-dose)

,,,,,
InterventionOptical density (Mean)
BaselineDay -7Day 1Day 8Day 29
AZD3965 Cohort 1 (5 mg OD)0.1230.4500.3970.4410.298
AZD3965 Cohort 2 (10 mg OD)0.7780.7310.9241.1111.060
AZD3965 Cohort 3 (20 mg OD)0.6140.5800.5930.6970.841
AZD3965 Cohort 4 (30 mg OD)0.1700.2040.2000.2060.144
AZD3965 Cohort 5 (15 mg BD)0.4850.2590.2410.2870.195
AZD3965 Cohort 6 (10 mg BD)0.1390.1400.1400.1490.156

Time to Maximum Observed Concentration of AZD3965

Plasma samples were analysed to determine the concentrations of AZD3965 using a previously developed LC-MS/MS method. For twice daily dosing, Day -7 data reflect the full daily dose and other timepoints reflect half the daily dose. (NCT01791595)
Timeframe: Part 1 (Cohorts 1-6): Day -7 (pre-dose; 0.25, 0.5, 1, 2, 4, 6, 24, 48 hours post-dose) and Day 1 (pre-dose, 0.25, 0.5, 1, 2, 4, 6, 24 hours post-dose [12 hours post-dose if BD])

,,,,,
InterventionHour (Median)
Day -7Day 1
AZD3965 Cohort 1 (5 mg OD)1.12
AZD3965 Cohort 2 (10 mg OD)1.12
AZD3965 Cohort 3 (20 mg OD)12.05
AZD3965 Cohort 4 (30 mg OD)1.11.1
AZD3965 Cohort 5 (15 mg BD)1.52
AZD3965 Cohort 6 (10 mg BD)1.921.075

Other Studies

10 other studies available for lactic acid and Lymphoma, Large B-Cell, Diffuse

ArticleYear
Type B lactic acidosis associated with diffuse large B-cell lymphoma and the Warburg effect.
    The Journal of international medical research, 2022, Volume: 50, Issue:1

    Topics: Acidosis, Lactic; Adult; Humans; Hypoglycemia; Lactic Acid; Lymphoma, Large B-Cell, Diffuse; Male; P

2022
Clinical presentation of Warburg effect in aggressive lymphoma: a case report.
    Journal of medical case reports, 2023, Aug-23, Volume: 17, Issue:1

    Topics: Acidosis, Lactic; Aged; Aggression; Cognition; Female; Humans; Lactic Acid; Lymphoma, Large B-Cell,

2023
Identification of lactate regulation pattern on tumor immune infiltration, therapy response, and DNA methylation in diffuse large B-cell lymphoma.
    Frontiers in immunology, 2023, Volume: 14

    Topics: DNA Methylation; Humans; Lactic Acid; Lymphoma, Large B-Cell, Diffuse; Prognosis; Rituximab; Tumor M

2023
Inhibition of monocarboxyate transporter 1 by AZD3965 as a novel therapeutic approach for diffuse large B-cell lymphoma and Burkitt lymphoma.
    Haematologica, 2017, Volume: 102, Issue:7

    Topics: Antineoplastic Agents; Biomarkers; Burkitt Lymphoma; Cell Death; Cell Line, Tumor; Drug Resistance,

2017
62-Year-Old Man With Encephalopathy and Fatigue After Allogeneic Bone Marrow Transplant.
    Mayo Clinic proceedings, 2018, Volume: 93, Issue:8

    Topics: Bone Marrow Transplantation; Brain Diseases; Consciousness Disorders; Cytomegalovirus Infections; Ep

2018
Successful Intensive Care Treatment of Severe Lactic Acidosis and Tumor Lysis Syndrome Related to Intravascular Lymphoma.
    Journal of Nippon Medical School = Nippon Ika Daigaku zasshi, 2020, Mar-11, Volume: 87, Issue:1

    Topics: Acidosis; Antineoplastic Combined Chemotherapy Protocols; Critical Care; Cyclophosphamide; Doxorubic

2020
Uncovering molecular abnormalities leading to the Warburg effect in primary refractory diffuse large B-cell lymphoma.
    Blood cancer journal, 2016, 12-02, Volume: 6, Issue:12

    Topics: Acidosis, Lactic; Aged; Antineoplastic Combined Chemotherapy Protocols; Chromosome Aberrations; Drug

2016
Lactate imaging with Hadamard-encoded slice-selective multiple quantum coherence chemical-shift imaging.
    Magnetic resonance in medicine, 2008, Volume: 60, Issue:2

    Topics: Algorithms; Animals; Biomarkers, Tumor; Cell Line, Tumor; Data Compression; Lactic Acid; Lymphoma, L

2008
NMR metabolic and physiological markers of therapeutic response.
    Advances in experimental medicine and biology, 2011, Volume: 701

    Topics: Aged; Animals; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocol

2011
In vivo MRS markers of response to CHOP chemotherapy in the WSU-DLCL2 human diffuse large B-cell lymphoma xenograft.
    NMR in biomedicine, 2008, Volume: 21, Issue:7

    Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cell Line, Tumor; Cell P

2008