Clinical trial NCT04038359: A Phase 2 Study Comparing 2 Intermittent Dosing Schedules of Duvelisib in Participants With Indolent Non-Hodgkin Lymphoma
Official title: A Phase 2, Randomized, Open-label, 2-Arm Study Comparing 2 Intermittent Dosing Schedules of Duvelisib in Subjects With Indolent Non-Hodgkin Lymphoma (iNHL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Indolent Non-Hodgkin Lymphoma
Keywords: PI3K Inhibitor
Lead sponsor: SecuraBio
Sponsor class: INDUSTRY
First posted: 2019-07-30
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study examined the effects of predefined 2-week duvelisib dose holidays on tumor responses and safety/tolerability.

Detailed description: This was a Phase 2, randomized, open-label, 2-arm study designed to evaluate the efficacy and safety of prescribed drug holidays of duvelisib treatment in participants with relapsed or refractory (R/R) indolent non-Hodgkin lymphoma (iNHL) who have received at least 1 prior systemic therapy.

Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group performance status ≤ 2
* Histologically confirmed diagnosis of iNHL (subtypes include follicular lymphoma \[FL\] Grades 1 to 3a), marginal zone lymphoma (splenic, nodal, or extranodal), or small lymphocytic lymphoma
* Must have received 1 prior systemic regimen for iNHL
* Must have documented radiologic evidence of disease progression, at least 1 bi-dimensionally measurable lesion ≥ 1.5 centimeters (which has not been previously irradiated), according to 2007 revised International Working Group criteria, and be a candidate for a subsequent line of therapy.
* Must have adequate organ function defined by the following laboratory parameters:

  * Absolute neutrophil count ≥ 1.0 × 10\^9/liter (L)
  * Platelet count ≥ 75 × 10\^9/L
  * Hemoglobin ≥ 8 grams/deciliter
  * Estimated creatinine clearance ≥ 60 milliliters/minute, as determined by the Cockcroft-Gault method
  * Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (exception: participants with Gilbert's Syndrome may have a bilirubin \> 1.5 × ULN)
  * Aspartate transaminase/serum glutamic-oxaloacetic transaminase and alanine aminotransferase/serum pyruvic transaminase ≤ 3.0 × ULN

Exclusion Criteria:

* Anticancer treatment, major surgery, or use of any investigational drug within 28 days before the start of study intervention; palliative radiation therapy is allowed if \> 7 days before planned first dose of study interventions, and any toxicity is Grade ≤ 1
* Clinical or histological evidence of transformation to a more aggressive subtype of lymphoma or grade 3b FL or Richters' transformation or chronic lymphocytic leukemia
* Prior allogeneic hematopoietic stem cell transplant; prior treatment with a PI3K inhibitor
* History of drug-induced colitis or pneumonitis; tuberculosis treatment ≤ 2 years prior to randomization; administration of a live or live attenuated vaccine within 6 weeks of randomization
* Ongoing treatment with chronic immunosuppressants or systemic steroids or treatment for systemic bacterial, fungal, or viral infection
* Active cytomegalovirus or Epstein-Barr virus infection
* Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus, or herpes zoster at screening
* Concurrent administration of medications or foods that are strong inhibitors or inducers of cytochrome P450 3A. No prior use within 2 weeks before the start of study intervention.
* Baseline QT interval corrected with Fridericia's method \> 500 milliseconds
* Concurrent active malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix, bladder cancer, or prostate cancer not requiring treatment. Participants with previous malignancies are eligible if they have been disease-free for 2 years or more.
* Unstable or severe uncontrolled medical condition that would, in the Investigator's judgment, increase the participant's risk to participating in this study.

Primary outcomes:
measure: Overall Response Rate (ORR) According to the 2007 Revised International Working Group (IWG) Criteria
timeFrame: Up to 14 months
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Up to 2 years
measure: ORR At Specific Timepoints
timeFrame: 6, 12, 18, and 24 months after first dose of study intervention
measure: Duration of Response (DOR)
timeFrame: Up to 2 years
measure: Overall Survival (OS)
timeFrame: Up to 2 years
measure: Lymph Node Response Rate (LNRR)
timeFrame: 14 months
measure: Time To First Response (TTFR)
timeFrame: Up to 14 months
measure: Time To Treatment Failure (TTF)
timeFrame: Up to 2 years
measure: ORR According to 2014 Lugano Criteria
timeFrame: Up to 14 months
Other outcomes:
Locations:
city: Fort Myers
country: United States
facility: Florida Cancer Specialists - Fort Myers
state: Florida
city: Lecanto
country: United States
facility: Florida Cancer Specialists & Research Institute - Lecanto
state: Florida
city: Orange City
country: United States
facility: Mid-Florida Cancer Centers
state: Florida
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center
state: Illinois
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Hradec Králové
country: Czechia
facility: FN Hradec Kralove
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Bonn
country: Germany
facility: Universitaetsklinikum Bonn AöR
city: Meldola
country: Italy
facility: Oncology Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori
state: Forli
city: Milano
country: Italy
facility: IEO - Istituto Europeo di Oncologia, IRCCS
city: Reggio Emilia
country: Italy
facility: AUSL di Reggio Emilia IRCCS, Arcispedale Santa Maria Nuova di Reggio Emilia
city: Terni
country: Italy
facility: Azienda Ospedaliera Santa Maria di Terni
city: Varese
country: Italy
facility: Ospedale di Circolo, PO Varese, AO Ospedale di Circolo e Fondazione Macchi
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center - Oncology
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center - Hematology-Oncology
city: Slupsk
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o.
state: Pomorskie
city: Katowice
country: Poland
facility: Pratia Onkologia Katowice
city: Skórzewo
country: Poland
facility: Centrum Medyczne Pratia Poznan
city: Moscow
country: Russian Federation
facility: State Budgetary Healthcare Institution of Moscow City Moscow Multidisciplinary Clinical Center "Kommunarka" of the Department of Healthcare of Moscow City
city: Moscow
country: Russian Federation
facility: City Clinical Hospital n.a. Botkin
city: Sankt-Peterburg
country: Russian Federation
facility: First Saint-Petersburg State Medical University n.a. I.P. Pavlov
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow & Clyde - CRUK Clinical Trials Unit
city: Liverpool
country: United Kingdom
facility: Royal Liverpool Hospital [Hematology/Transfusion Medicine]
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Foundation Trust
Study officials:
References: