A Study of Duvelisib in Participants With Relapsed or Refractory Peripheral T-cell Lymphoma (PTCL)
- Registration Number
- NCT03372057
- Lead Sponsor
- SecuraBio
- Brief Summary
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).
- Detailed Description
The study had 2 phases, a Dose Optimization Phase and an Expansion Phase.
In the Dose Optimization Phase, participants were randomly assigned to 1 of 2 study cohorts, as follows:
* Cohort 1: Duvelisib per oral (PO) twice daily (BID) at a starting dose of 25 milligrams (mg), with potential escalation on a per-participant basis to 50 mg and then 75 mg, based on the participant's response to and tolerance of therapy, in 28-day cycles.
* Cohort 2: Duvelisib 75 mg PO BID, administered in 28-day cycles.
A total of 20 participants were to be enrolled in the Dose Optimization Phase, with 10 participants per cohort. Based on the safety and activity data obtained in the Dose Optimization Phase of the study, the Expansion Phase dose of duvelisib was to be determined.
In the Expansion Phase, approximately 100-130 participants were to be enrolled and receive duvelisib dose in 28-day cycles as determined in Dose Optimization Phase.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 156
-
Age ≥ 18 years of age
-
Diagnosis of one of the following histologic subtypes of PTCL, pathologically confirmed, as defined by the World Health Organization:
- Peripheral T-cell lymphoma-not otherwise specified;
- Angioimmunoblastic T-cell lymphomas;
- Anaplastic large cell lymphoma (ALCL); or
- Natural-killer/T-cell lymphoma
-
Received at least 2 cycles of one standard regimen for newly diagnosed advanced PTCL, and one of the following:
- failed to achieve at least a PR after 2 or more cycles of standard therapy;
- failed to achieve a CR after completion of standard therapy; and/or
- persistent or progressive disease after an initial response
-
For participants with CD30+ ALCL, failed or are ineligible or intolerant to brentuximab vedotin
-
Measurable disease as defined by Lugano for PTCL, that is, at least 1 measurable disease lesion > 1.5 centimeters in at least one dimension by conventional techniques (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography [CT], CT with contrast, magnetic imaging resonance)
- Primary leukemic PTCL subtypes (that is, T-cell prolymphocytic leukemia, T-cell large granular lymphocytic leukemia, adult T-cell leukemia/lymphoma and aggressive NK-cell leukemia) or transformed mycosis fungoides
- Received prior allogeneic transplant
- Received prior treatment with a PI3K inhibitor
- Known central nervous system involvement by PTCL
- Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine) or systemic steroids > 20 mg of prednisone (or equivalent) once daily
- Ongoing treatment for systemic bacterial, fungal, or viral infection at Screening
- Known hypersensitivity to duvelisib and/or its excipients
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Optimization Phase: Cohort 1 Duvelisib Duvelisib PO BID at a starting dose of 25 mg, with potential escalation on a per-participant basis to 50 mg and then 75 mg, based on the participant's response to and tolerance of therapy, in 28-day cycles. Dose Optimization Phase: Cohort 2 Duvelisib Duvelisib 75 mg PO BID, administered in 28-day cycles. Expansion Phase Duvelisib Duvelisib PO BID at a starting dose of 75 mg for the first 2 cycles, followed by a mandatory reduction to 25 mg BID thereafter for those participants with complete response (CR), partial response (PR) or stable disease (SD), in 28-day cycles (dose determined in Optimization Phase).
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) as Assessed by the Investigator Using the Lugano Criteria 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.
ORR as Assessed by the Independent Review Committee (IRC) Using the Lugano Criteria 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.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) as Assessed by the Investigator Using the Lugano Criteria 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.
Progression-free Survival (PFS) as Assessed by the Investigator Using the Lugano Criteria 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.
Disease Control Rate (DCR) As Assessed by the Investigator Using the Lugano Criteria 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.
DOR as Assessed by the IRC Using the Lugano Criteria 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.
PFS as Assessed by the IRC Using the Lugano Criteria 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.
DCR as Assessed by the IRC Using the Lugano Criteria 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.
Overall Survival (OS) 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.
Plasma Concentration of IPI-145 (Duvelisib) and IPI-656 (Metabolite) 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).
Trial Locations
- Locations (36)
Japanese Site 7
🇯🇵Niigata, Japan
Japanese Site 1
🇯🇵Okayama, Japan
Japanese Site 8
🇯🇵Fukuoka, Japan
Japanese Site 5
🇯🇵Kobe, Japan
Japanese Site 3
🇯🇵Miyagi, Japan
Japanese Site 6
🇯🇵Nagoya, Japan
Japanese Site 2
🇯🇵Tokyo, Japan
Japanese Site 4
🇯🇵Tokyo, Japan
City of Hope National Medical Center
🇺🇸Duarte, California, United States
University of California - Irvine
🇺🇸Irvine, California, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of California - Los Angeles
🇺🇸Los Angeles, California, United States
Emory University Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Northwestern University - Feinberg School of Medicine
🇺🇸Chicago, Illinois, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
Stony Brook Cancer Center
🇺🇸Stony Brook, New York, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Novant Health
🇺🇸Charlotte, North Carolina, United States
Duke University
🇺🇸Durham, North Carolina, United States
The Ohio State University
🇺🇸Columbia, Ohio, United States
Toledo Cancer Center
🇺🇸Toledo, Ohio, United States
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Baylor Research Institute - Charles Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Universitätsklinikum Halle (Saale) - Klinik und Poliklinik für Innere Medizin IV
🇩🇪Halle, Sachsen-Anhalt, Germany
Universitätsklinikum Carl Gustav Carus
🇩🇪Dresden, Sachsen, Germany
ASST Papa Giovanni XXIII - Medicina Trasfusionale ed Ematologia - Bergamo
🇮🇹Bergamo, Italy
A.O.di Bologna Policl.S.Orsola
🇮🇹Bologna, Italy
Ieo, Irccs
🇮🇹Milano, Italy
Policlinico Universitario Agostino Gemelli, Università Cattolica del Sacro Cuore
🇮🇹Roma, Italy
Azienda Ospedaliera Santa Maria di Terni
🇮🇹Terni, Italy
Christie Hospital NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, United Kingdom