lactic acid and Burkitt Lymphoma

lactic acid has been researched along with Burkitt Lymphoma in 5 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.

Burkitt Lymphoma: A form of undifferentiated malignant LYMPHOMA usually found in central Africa, but also reported in other parts of the world. It is commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. B-cell antigens are expressed on the immature cells that make up the tumor in virtually all cases of Burkitt lymphoma. The Epstein-Barr virus (HERPESVIRUS 4, HUMAN) has been isolated from Burkitt lymphoma cases in Africa and it is implicated as the causative agent in these cases; however, most non-African cases are EBV-negative.

Research

Studies (5)

Authors

Clinical Trials (1)

Trial Overview

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)

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)

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

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

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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])

Other Studies

5 other studies available for lactic acid and Burkitt Lymphoma