vorinostat and HIV Coinfection

vorinostat has been researched along with HIV Coinfection in 53 studies

Vorinostat: A hydroxamic acid and anilide derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used in the treatment of CUTANEOUS T-CELL LYMPHOMA and SEZARY SYNDROME.
vorinostat : A dicarboxylic acid diamide comprising suberic (octanedioic) acid coupled to aniline and hydroxylamine. A histone deacetylase inhibitor, it is marketed under the name Zolinza for the treatment of cutaneous T cell lymphoma (CTCL).

Research

Studies (53)

Authors

Clinical Trials (15)

Trial Overview

Trial Outcomes

Percent of Participants With a Grade 3 or Higher Treatment-Related Adverse Event (AE)

The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017 was used to measure safety where Grade 3 is defined as severe and Grade 4 is defined as potentially life-threatening. Treatment-Related AEs assessments are considered related to study product as possible, probable, or definite as defined in the protocol. (NCT03803605)
Timeframe: First day of study treatment through end of study, a total of approximately 36 weeks

Change From Baseline in Cell-associated HIV-1 RNA in CD4+ T Cells

Baseline is defined as the average of the pre-entry and entry values. Change was calculated as the value of Cell-associated HIV-1 RNA on Day 38 (5 hours post vorinostat) minus the value at baseline. (NCT03382834)
Timeframe: Pre-entry, entry, and Day 38

Change From Baseline in Total HIV-1 DNA Levels in CD4+ T Cells

Baseline is defined as the average of the pre-entry and entry values. Change was calculated as the value of Total HIV-1 DNA on Day 38 (5 hours post vorinostat) minus the value at baseline. (NCT03382834)
Timeframe: Pre-entry, entry, and Day 38

Proportion of Participants With New Grade 3 or Greater Adverse Events

Proportion of participants with new Grade 3 or greater adverse events that are considered definitely, probably, or possibly related to study treatment (as judged by the core protocol team). The DAIDS AE Grading Table (corrected Version 2.1, July 2017) was used. (NCT03382834)
Timeframe: Measured from study entry through Day 65

Number of Participants With HIV-1 RNA Levels (Measured by Single Copy Assay) Greater or Equal to the Lower Limit of Quantification

Number of participants with HIV-1 RNA levels measured by single copy assay (SCA) greater or equal to the lower limit of quantification (LOQ). The lower limit of quantification for this study was 0.47 copies/mL. (NCT03382834)
Timeframe: Pre-entry, entry, Day 28, Day 35, Day 38 (5 hours post vorinostat), Day 45, Day 65

Histone H4 Acetylation

Histone H4 acetylation using a H4K5/8/12/16 immunoassay with thawed PBMC derived cell lysates added to an ELISA using anti-H4 monoclonal antibody (NCT02336074)
Timeframe: 12 weeks

Quantitative Viral Outgrowth

Number of Participants with undetectable quantitative viral outgrowth (NCT02336074)
Timeframe: At week 16

Total HIV DNA From CD4 T-cells

The average of two measures taken at post-randomisation week 16 and 18 (NCT02336074)
Timeframe: Averaged across post-randomisation week 16 and 18

Viral Inhibition

"CD8+ T cell antiviral suppressive activity was expressed as percentage elimination and determined as follows: [(fraction of p24+ cells in CD4+ T cells cultured alone) - (fraction of p24 + in CD4+ T cells cultured with CD8+ cells)]/(fraction of p24+ cells in CD4+ T cells cultured alone) × 100.~Viral inhibition Assay" (NCT02336074)
Timeframe: 12 weeks

CD8+ T-cell Responses

Percentage of CD8+ CD107a+ IFNγ+ T cells , assessed using an optimized and qualified flow cytometry panel. (NCT02336074)
Timeframe: 12 weeks

Percentage of CD4+ CD154+ IFNγ+ T Cells

Percentage of CD4+ CD154+ IFNγ+ T cells , assessed using an optimized and qualified flow cytometry panel. (NCT02336074)
Timeframe: 12 weeks

Event-free Survival (EFS) (Phase II)

The percentage of participants surviving without events (relapse or death) one year after starting treatment. (NCT01193842)
Timeframe: 1 year

Overall Survival (OS) (Phase II)

The percentage of participants surviving one year after starting treatment. (NCT01193842)
Timeframe: 1 year

Percentage of Participants With Complete Response (CR) as Assessed by Response Evaluation Criteria in Solid Tumors (Phase II)

"Percentage of participants with complete response as assessed by Response Evaluation Criteria in Solid Tumors (Phase II) according to treatment arm. Participants are planned to be treated for a total of 6 cycles (21 day cycle length). Participants with CR after Cycle 4 will receive two additional cycles of chemotherapy and complete 6 cycles of chemotherapy. Participants who achieve a partial response (PR) only after Cycle 4 may continue on protocol therapy or they may be removed from the study at the AMC discretion of the physician (local Principal Investigator). Participants with stable disease after 4 cycles (i.e., who did not achieve at least a PR) or progressive disease at any time will be removed from study.~In phase II, there are two arms: Vorinostat RPTD+rituximab-DA-EPOCH arm (VR-DA-EPOCH) and Rituximab-DA-EPOCH arm (DA-R-EPOCH)." (NCT01193842)
Timeframe: Up to 6 months

Recommended Phase II Dose of Vorinostat Determined According to Dose-limiting Toxicities Graded Using Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) (Phase I)

Recommended phase II dose of vorinostat is defined as the dose level at which 0/6 or 1/6 subjects experience dose limiting toxicity (DLT) with the next higher dose having at least 2/3 or 2/6 subjects encountering DLT (Phase I). Toxicities will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Using a 3+3 design, the recommended phase II dose is defined as the level at which 0/6 or 1/6 patients experiences at dose-limiting toxicity in the first cycle. (NCT01193842)
Timeframe: 21 days

Change in CD8 Cell Counts (Phase I)

Differences from baseline (specified follow-up assessment minus baseline) in absolute CD8 counts. (NCT01193842)
Timeframe: Baseline up to 12 months

Change in Plasma Associated Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) (Phase I)

Differences from baseline (specified follow-up assessment minus baseline) in HIV viral load. Undetectable viral load results were treated as 0 values. (NCT01193842)
Timeframe: Baseline up to 12 months

Changes in Absolute CD4 Cell Counts (Phase I)

Differences from baseline (specified follow-up assessment minus baseline) in absolute CD4 counts. (NCT01193842)
Timeframe: Baseline up to 12 months

Changes in Epstein-Barr Virus (EBV) Viral Load

Differences from baseline (specified follow-up assessment minus baseline) in EBV viral load. (NCT01193842)
Timeframe: Baseline up to 12 months

Changes in Human Herpes Virus (HHV)-8 Viral Load

Differences from baseline (specified follow-up assessment minus baseline) in (HHV)-8 viral load. (NCT01193842)
Timeframe: Baseline up to 12 months

Changes in Human Herpes Virus (HHV)-8 Viral Load

Differences from baseline (specified follow-up assessment minus baseline) in (HHV)-8 viral load. (NCT01193842)
Timeframe: Baseline up to 12 months

Changes in Human Immunodeficiency Virus (HIV) Viral Load

Differences from baseline (specified follow-up assessment minus baseline) in HIV viral load. Undetectable viral load results were treated as 0 values. (NCT01193842)
Timeframe: Baseline up to 12 months

Percentage of Participant Experiencing Adverse Events (AEs) for Each Treatment Arm as Assessed by Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) (Phase II)

The percentage of participants with AEs and their worst severity will be tabulated for each treatment arm. If a participant has more than one AE, the most severe AE is analyzed. All adverse events will be assessed by the investigator from the first dose of protocol therapy through the post-treatment discontinuation visit. Participants are planned to be treated for a total of 6 cycles (21 day cycle length), or roughly 4 months. After this evaluation, assessment and reporting of AEs will only be required for all grade 5 AEs and any serious AE (SAE) that the investigator considers related to protocol therapy. (NCT01193842)
Timeframe: Up to 5 years

Pharmacokinetic Clearance (Phase I)

Serial plasma samples for pharmacokinetic analysis were collected at 24-48, 48-72, and 72-96 hours after the start of the first chemotherapy infusion. Doxorubicin, etoposide, and vincristine concentrations were determined using a validated liquid chromatography-tandem mass spectrometry method. The clearance was determined by dividing the drug-infusion rate by the steady-state concentrations, which was the average of the three time points. (NCT01193842)
Timeframe: 24-48, 48-72, and 72-96 hours after the start of the first chemotherapy infusion

Tumor Response (Phase I)

The percentage of participants whose best tumor response is complete response (CR) or partial response (PR). Based on clinical, radiologic (CT), and pathologic criteria, CR requires 1) complete disappearance of all detectable disease and disease-related symptoms if present before therapy, 2) bone marrow aspirate and biopsy to confirm a CR if initially positive or if clinically indicated by new abnormalities in the peripheral blood counts or blood smear, 3) negative PET results, depending on typically, variably, or unknown pre-treatment FDG status, and 4) spleen and/or liver, if considered to be enlarged before therapy on physical examination or CT scan, not being palpable on physical examination and considered normal size by imaging studies, and nodules related to lymphoma disappeared. PR includes 1) ≥50% decrease in sum of product of diameters (SPD), 2) no increase in size of nodes, liver, or spleen, 3) splenic/hepatic nodules regressed by ≥ 50% SPD, 4) no new sites of disease (NCT01193842)
Timeframe: Up to 2 years post treatment

Number of Participants Developing Cancer Within 5 Years Following >/= 8 Vorinostat Dose Exposures

Development of a new cancer within the 5 years of taking their last dose of VOR 400 mg PO.All participants receiving one or more doses of VOR 400 mg PO in any and all Arms of the study. Pre-specified to be reported as one group. (NCT01319383)
Timeframe: From last dose Vorinostat to 5 years afterwards

Number of Participants Exhibiting an in Vivo Resting CD4+ T Cell- Associated HIV RNA (RCVL) Increase After Receiving a Single Dose of VOR 400 mg PO

Participants in Arm 1 and 2 were analyzed in Step 2 for an in vivo increase in resting CD4+ T cell- associated HIV RNA (RCVL) after administration of a single dose of VOR 400 mg PO (NCT01319383)
Timeframe: Arm1: Baseline, Visit 5 and Arm 2: Baseline and Visit 3

Number of Participants Exhibiting an in Vivo Resting CD4+ T-cell-associated HIV RNA (Rc-RNA) Increase Following Each of Two Multiple Dose Cycles (11 Doses/Cycle)

Participants in Arm 1, Step 3 were analyzed for an in vivo increase in the resting CD4+ T cell- associated HIV RNA (RCVL) after 11 doses of VOR 400 mg PO. This cycle was repeated after a 5 - 8 week rest period for a 2nd series and measurement. (NCT01319383)
Timeframe: Baseline, Visit 18, Visit 29

Number of Participants Exhibiting an in Vivo Resting CD4+ T-cell-associated HIV RNA (Rc-RNA) Increase Following Multiple (n = 10) Interval Doses

Participants in Arm 2, Step 4 were analyzed for an in vivo increase in the resting CD4+ T cell- associated HIV RNA (RCVL) after administration of 10 doses of VOR 400 mg PO, given 72 hours apart. (NCT01319383)
Timeframe: Baseline, Visit 9

Number of Participants With a Significant in Vivo Response in Resting Cell Infection (RCI) and HIV RNA After Paired Doses

Induction of significant in vivo RCI and RCLV response after 2 doses of VOR 400 mg PO administered 48 hours apart or 72 hours apart (NCT01319383)
Timeframe: Baseline, Visit 6

Number of Participants With Confirmed Hematologic Toxicity >/= Grade 2 and Related to VOR Per Division of AIDS (DAIDS) Grading Table

DAIDS Grading Table- Grade 1- mild, Grade 2- moderate; Grade 3- severe Grade 4- potentially life-threatening. Pre specified to combine all participants into one arm. (NCT01319383)
Timeframe: 24 hrs following single dose and 1 week after last of multiple dose sequence

Number of Participants With Confirmed Non-hematologic Toxicity >/= Grade 3 and Related to VOR Per Division of AIDS (DAIDS) Grading Table

DAIDS Grading Table- Grade 1- mild, Grade 2- moderate; Grade 3- severe Grade 4- potentially life-threatening. Pre specified to combine all participants into one arm. (NCT01319383)
Timeframe: 24 hrs following single dose and 1 week after last of multiple dose sequence

Number of Participants With Measurable Changes in Plasma HIV-1 RNA

Assess for detectible HIV-1 RNA > 150 copies/mL, confirmed by repeat evaluation, following VOR dose. By standard assay and single copy assay. Pre specified to combine all participants into one arm. (NCT01319383)
Timeframe: 1 week after last VOR dose

CD8 CD38 (Mean of Fluorescence)

the CD38-activation marker on CD8 T-cells (CD8/CD38). (NCT02071095)
Timeframe: Day 8

NK Cell Number

Natural killer cells or NK cells are part of the innate immune defense against infection and cancer. (NCT02071095)
Timeframe: at 48 weeks

Number Participants With Adverse Events

Safety measured by number of participants with adverse events. (NCT02071095)
Timeframe: Up to 48 weeks

Percent Change in CD4+ Tcell-associated HIV-1 RNA as Compared to Baseline

CD4+ Tcell-associated HIV-1 RNA to determine whether Poly-ICLC disrupts viral latency in HIV-1-infected individuals on anti-retroviral therapy.Viral transcription assessed by monitoring cell associated HIV-1 RNA. Percent change compared to baseline. (NCT02071095)
Timeframe: Baseline, Day 2, Day 4, Day 8, Day 28

Plasma Interferon-gamma-inducible Protein-10 (IP-10) Level

One of the biomarkers of cellular immune activation and exhaustion quantified by flow cytometry. Normal range is 7.8-500 pg/ml. (NCT02071095)
Timeframe: Day 2 and Day 4

Reviews

5 reviews available for vorinostat and HIV Coinfection

Trials

7 trials available for vorinostat and HIV Coinfection

Other Studies

41 other studies available for vorinostat and HIV Coinfection