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NCT03372057: PRIMO

A Study of Duvelisib in Participants With Relapsed or Refractory Peripheral T-cell Lymphoma (PTCL)

Completed Phase 2 Results posted Last updated 7 March 2025
What this trial tests

Phase 2 trial testing Duvelisib in Peripheral T-cell Lymphoma in 156 participants. Completed in 22 December 2023.

Timeline
22 February 2018
Primary endpoint
22 December 2023
22 December 2023

Quick facts

Lead sponsorSecuraBio
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment156
Start date22 February 2018
Primary completion22 December 2023
Estimated completion22 December 2023
Sites36 locations across Italy, Japan, United Kingdom, Germany, United States

Drugs / interventions tested

Conditions studied

Sponsor

SecuraBio — full company profile →

Who can join

18 and older, any sex, with Peripheral T-cell Lymphoma. 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.

Overall Response Rate (ORR) as Assessed by the Investigator Using the Lugano Criteria Primary · 56 days (2 cycles; 28-day cycles)

ORR was defined as the percentage of participants with CR + PR, as assessed by the investigator using the Lugano criteria, for participants receiving the optimal dose of duvelisib for at least one cycle of study therapy.

GroupValue95% CI
Dose Optimization Phase: Cohort 153.826.7 – 80.9
Dose Optimization Phase: Cohort 253.826.7 – 80.9
ORR as Assessed by the Independent Review Committee (IRC) Using the Lugano Criteria Primary · 56 days (2 cycles; 28-day cycles)

ORR was defined as the percentage of participants with CR + PR, as assessed by the IRC using the Lugano criteria, for participants receiving the optimal dose of duvelisib for at least one cycle of study therapy.

GroupValue95% CI
Expansion Phase48.039.1 – 56.8
Duration of Response (DOR) as Assessed by the Investigator Using the Lugano Criteria Secondary · Up to 70 months

DOR was defined for participants with CR or PR as the time from the date of the first documentation of response (CR or PR) to the date of the first documentation of progressive disease (PD) or death due to any cause. Participants who withdraw from the study for any reason prior to PD and participants who had ongoing response at the time of the data cut were censored at the date of their last response assessment.

GroupValue95% CI
Dose Optimization Phase: Cohort 14.221.87 – NA
Dose Optimization Phase: Cohort 23.321.77 – NA
Progression-free Survival (PFS) as Assessed by the Investigator Using the Lugano Criteria Secondary · Up to 70 months

PFS was defined as the time from the date of first treatment to the date of the first radiographic disease progression or death due to any cause, whichever occurred first.

GroupValue95% CI
Dose Optimization Phase: Cohort 13.551.05 – 8.54
Dose Optimization Phase: Cohort 23.551.81 – 13.14
Disease Control Rate (DCR) As Assessed by the Investigator Using the Lugano Criteria Secondary · Up to 8 weeks

DCR was defined as the percentage of participants with a best overall response of CR or PR or with a best overall response of stable disease (SD) sustained for at least 8 weeks.

GroupValue95% CI
Dose Optimization Phase: Cohort 161.535.1 – 88.0
Dose Optimization Phase: Cohort 261.535.1 – 88.0
DOR as Assessed by the IRC Using the Lugano Criteria Secondary · Up to 70 months

DOR was defined for participants with CR or PR as the time from the date of the first documentation of response (CR or PR) to the date of the first documentation of PD or death due to any cause. Participants who withdrew from the study for any reason prior to PD and participants who had ongoing response at the time of the data cut were censored at the date of their last response assessment.

GroupValue95% CI
Expansion Phase7.96.4 – 21.00
PFS as Assessed by the IRC Using the Lugano Criteria Secondary · Up to 70 months

PFS was defined as the time from the date of first treatment to the date of the first radiographic disease progression or death due to any cause, whichever occurred first.

GroupValue95% CI
Expansion Phase3.41.8 – 3.9
DCR as Assessed by the IRC Using the Lugano Criteria Secondary · Up to 8 weeks

DCR was defined as the percentage of participants with a best overall response of CR or PR or with a best overall response of SD sustained for at least 8 weeks.

GroupValue95% CI
Expansion Phase49.640.8 – 58.4
Overall Survival (OS) Secondary · Up to 70 months

OS was defined as the time from the date of first treatment to the date of death due to any cause. Participants without documented death were censored at last alive date.

GroupValue95% CI
Dose Optimization Phase: Cohort 16.705.22 – NA
Dose Optimization Phase: Cohort 210.586.67 – 44.62
Expansion Phase12.48.4 – 22.7
Plasma Concentration of IPI-145 (Duvelisib) and IPI-656 (Metabolite) Secondary · Day 15 of Cycles 1 and 2 (4 hours postdose) (28-day cycles)

Blood samples were taken for the analyses of duvelisib and IPI-656 in plasma at designated time points. Results are reported as nanograms/milliliter (ng/mL).

Duvelisib: Cycle 1, Day 15
GroupValue95% CI
Dose Optimization Phase: Cohort 11238.1± 787.53
Dose Optimization Phase: Cohort 22070.0± 889.39
Expansion Phase2873.7± 1709.15
Duvelisib: Cycle 2, Day 15
GroupValue95% CI
Dose Optimization Phase: Cohort 11492.5± 1019.10
Expansion Phase2648.2± 1336.94
Metabolite (IPI-156): Cycle 1, Day 15
GroupValue95% CI
Dose Optimization Phase: Cohort 11310.4± 1408.99
Dose Optimization Phase: Cohort 21580.9± 772.13
Expansion Phase2387.5± 1919.33
Metabolite (IPI-156): Cycle 2, Day 15
GroupValue95% CI
Dose Optimization Phase: Cohort 1894.8± 441.55
Expansion Phase2427.0± 1655.89

Adverse events — posted to ClinicalTrials.gov

Time frame: From start of treatment (Day 1) to end of study (70 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dose Optimization Phase: Cohort 1
Serious: 14/20 (70%)
Deaths: 16/20
Dose Optimization Phase: Cohort 2
Serious: 9/13 (69%)
Deaths: 11/13
Expansion Phase
Serious: 60/123 (49%)
Deaths: 78/123

Serious adverse events (86 terms)

ReactionSystemDose Optimization Phase: C…Dose Optimization Phase: C…Expansion Phase
Disease progressionGeneral disorders
DiarrhoeaGastrointestinal disorders
PyrexiaGeneral disorders
PneumoniaInfections and infestations
SepsisInfections and infestations
Aspartate aminotransferase increasedInvestigations
Alanine aminotransferase increasedInvestigations
Febrile neutropeniaBlood and lymphatic system disorders
Atrial fibrillationCardiac disorders
ColitisGastrointestinal disorders
COVID-19 pneumoniaInfections and infestations
Urinary tract infectionInfections and infestations
HyponatraemiaMetabolism and nutrition disorders
DehydrationMetabolism and nutrition disorders
Acute kidney injuryRenal and urinary disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Autoimmune haemolytic anaemiaBlood and lymphatic system disorders
Sinus tachycardiaCardiac disorders
Cardiac arrestCardiac disorders
Cardiac failureCardiac disorders
TachycardiaCardiac disorders
Abdominal painGastrointestinal disorders
Other adverse events (130 terms — click to expand)

ReactionSystemDose Optimization Phase: C…Dose Optimization Phase: C…Expansion Phase
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
DiarrhoeaGastrointestinal disorders
Neutrophil count decreasedInvestigations
FatigueGeneral disorders
AnaemiaBlood and lymphatic system disorders
Platelet count decreasedInvestigations
NauseaGastrointestinal disorders
PyrexiaGeneral disorders
White blood cell count decreasedInvestigations
ConstipationGastrointestinal disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
Blood lactate dehydrogenase increasedInvestigations
PruritusSkin and subcutaneous tissue disorders
Oedema peripheralGeneral disorders
Lymphocyte count decreasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
VomitingGastrointestinal disorders
Blood creatinine increasedInvestigations
HypertensionVascular disorders
StomatitisGastrointestinal disorders
HyponatraemiaMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
RashSkin and subcutaneous tissue disorders
Abdominal painGastrointestinal disorders
Lipase increasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
Dry skinSkin and subcutaneous tissue disorders
Blood alkaline phosphatase increasedInvestigations
HyperglycaemiaMetabolism and nutrition disorders
HypotensionVascular disorders
Decreased appetiteMetabolism and nutrition disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Blood bilirubin increasedInvestigations
HypoalbuminaemiaMetabolism and nutrition disorders
DysgeusiaNervous system disorders
InsomniaPsychiatric disorders
DyspepsiaGastrointestinal disorders
Amylase increasedInvestigations

Most-reported serious reactions: Disease progression, Diarrhoea, Pyrexia, Pneumonia, Sepsis, Aspartate aminotransferase increased, Alanine aminotransferase increased, Febrile neutropenia.

Data from ClinicalTrials.gov NCT03372057 adverse events section.

Sponsor's own description

This is a multi-center, parallel cohort, open-label, Phase 2 study of duvelisib, an oral dual inhibitor of phosphoinositide-3-kinase-delta, gamma (PI3K-δ,γ), in participants with relapsed/refractory peripheral T-cell lymphoma (PTCL).

Publications & conference data

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

  1. Targeting PI3K in cancer: mechanisms and advances in clinical trials.
    Yang J, Nie J, Ma X, Wei Y, et al · · 2019 · cited 1142× · PMID 30782187 · DOI 10.1186/s12943-019-0954-x
  2. Role of PI3K/AKT pathway in cancer: the framework of malignant behavior.
    Jiang N, Dai Q, Su X, Fu J, et al · · 2020 · cited 419× · PMID 32333246 · DOI 10.1007/s11033-020-05435-1
  3. Tumor-associated macrophages: potential therapeutic strategies and future prospects in cancer.
    Li C, Xu X, Wei S, Jiang P, et al · · 2021 · cited 259× · PMID 33504575 · DOI 10.1136/jitc-2020-001341
  4. Recent Advances in the Treatment of Peripheral T-Cell Lymphoma.
    Laribi K, Alani M, Truong C, Baugier de Materre A. · · 2018 · cited 38× · PMID 29674443 · DOI 10.1634/theoncologist.2017-0524
  5. Biomarker-driven management strategies for peripheral T cell lymphoma.
    Mulvey E, Ruan J. · · 2020 · cited 29× · PMID 32448357 · DOI 10.1186/s13045-020-00889-z
  6. The Importance of Phosphoinositide 3-Kinase in Neuroinflammation.
    Wright B, King S, Suphioglu C. · · 2024 · cited 28× · PMID 39519189 · DOI 10.3390/ijms252111638
  7. Strategies to Overcome Failures in T-Cell Immunotherapies by Targeting PI3K-δ and -γ.
    Chandrasekaran S, Funk CR, Kleber T, Paulos CM, et al · · 2021 · cited 27× · PMID 34512641 · DOI 10.3389/fimmu.2021.718621
  8. Safety and efficacy of dual PI3K-δ, γ inhibitor, duvelisib in patients with relapsed or refractory lymphoid neoplasms: A systematic review and meta-analysis of prospective clinical trials.
    Wang Z, Zhou H, Xu J, Wang J, et al · · 2022 · cited 22× · PMID 36685572 · DOI 10.3389/fimmu.2022.1070660

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