Clinical trial NCT03372057: A Study of Duvelisib in Participants With Relapsed or Refractory Peripheral T-cell Lymphoma (PTCL)
Official title: A Multi-Center, Phase 2, Open-label, Parallel Cohort Study of Efficacy and Safety of Duvelisib in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma (PTCL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Peripheral T-cell Lymphoma
Keywords: Lymphoma
T-cell Lymphoma
Relapse
Refractory
PI3K-δ,γ
Lead sponsor: SecuraBio
Sponsor class: INDUSTRY
First posted: 2017-12-13
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years of age
2. Diagnosis of one of the following histologic subtypes of PTCL, pathologically confirmed, as defined by the World Health Organization:

   1. Peripheral T-cell lymphoma-not otherwise specified;
   2. Angioimmunoblastic T-cell lymphomas;
   3. Anaplastic large cell lymphoma (ALCL); or
   4. Natural-killer/T-cell lymphoma
3. Received at least 2 cycles of one standard regimen for newly diagnosed advanced PTCL, and one of the following:

   1. failed to achieve at least a PR after 2 or more cycles of standard therapy;
   2. failed to achieve a CR after completion of standard therapy; and/or
   3. persistent or progressive disease after an initial response
4. For participants with CD30+ ALCL, failed or are ineligible or intolerant to brentuximab vedotin
5. 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)

Exclusion Criteria:

1. 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
2. Received prior allogeneic transplant
3. Received prior treatment with a PI3K inhibitor
4. Known central nervous system involvement by PTCL
5. Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine) or systemic steroids \> 20 mg of prednisone (or equivalent) once daily
6. Ongoing treatment for systemic bacterial, fungal, or viral infection at Screening
7. Known hypersensitivity to duvelisib and/or its excipients

Primary outcomes:
measure: Overall Response Rate (ORR) as Assessed by the Investigator Using the Lugano Criteria
timeFrame: 56 days (2 cycles; 28-day cycles)
measure: ORR as Assessed by the Independent Review Committee (IRC) Using the Lugano Criteria
timeFrame: 56 days (2 cycles; 28-day cycles)
Secondary outcomes:
measure: Duration of Response (DOR) as Assessed by the Investigator Using the Lugano Criteria
timeFrame: Up to 70 months
measure: Progression-free Survival (PFS) as Assessed by the Investigator Using the Lugano Criteria
timeFrame: Up to 70 months
measure: Disease Control Rate (DCR) As Assessed by the Investigator Using the Lugano Criteria
timeFrame: Up to 8 weeks
measure: DOR as Assessed by the IRC Using the Lugano Criteria
timeFrame: Up to 70 months
measure: PFS as Assessed by the IRC Using the Lugano Criteria
timeFrame: Up to 70 months
measure: DCR as Assessed by the IRC Using the Lugano Criteria
timeFrame: Up to 8 weeks
measure: Overall Survival (OS)
timeFrame: Up to 70 months
measure: Plasma Concentration of IPI-145 (Duvelisib) and IPI-656 (Metabolite)
timeFrame: Day 15 of Cycles 1 and 2 (4 hours postdose) (28-day cycles)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Irvine
country: United States
facility: University of California - Irvine
state: California
city: Los Angeles
country: United States
facility: University of California - Los Angeles
state: California
city: Atlanta
country: United States
facility: Emory University Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: Northwestern University - Feinberg School of Medicine
state: Illinois
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Stony Brook
country: United States
facility: Stony Brook Cancer Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Charlotte
country: United States
facility: Novant Health
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Columbia
country: United States
facility: The Ohio State University
state: Ohio
city: Toledo
country: United States
facility: Toledo Cancer Center
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor Research Institute - Charles Sammons Cancer Center
state: Texas
city: Halle
country: Germany
facility: Universitätsklinikum Halle (Saale) - Klinik und Poliklinik für Innere Medizin IV
state: Sachsen-Anhalt
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
state: Sachsen
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII - Medicina Trasfusionale ed Ematologia - Bergamo
city: Bologna
country: Italy
facility: A.O.di Bologna Policl.S.Orsola
city: Milano
country: Italy
facility: Ieo, Irccs
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli, Università Cattolica del Sacro Cuore
city: Terni
country: Italy
facility: Azienda Ospedaliera Santa Maria di Terni
city: Fukuoka
country: Japan
facility: Japanese Site 8
city: Kobe
country: Japan
facility: Japanese Site 5
city: Miyagi
country: Japan
facility: Japanese Site 3
city: Nagoya
country: Japan
facility: Japanese Site 6
city: Niigata
country: Japan
facility: Japanese Site 7
city: Okayama
country: Japan
facility: Japanese Site 1
city: Tokyo
country: Japan
facility: Japanese Site 2
city: Tokyo
country: Japan
facility: Japanese Site 4
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
Study officials:
References: