A Phase 2 Study Comparing 2 Intermittent Dosing Schedules of Duvelisib in Subjects With Indolent Non-Hodgkin Lymphoma
- Registration Number
- NCT04038359
- Lead Sponsor
- SecuraBio
- Brief Summary
This study will examine the effects of predefined 2-week duvelisib dose holidays on tumor responses and safety/tolerability.
- Detailed Description
This is a Phase 2, randomized, open-label, 2-arm study designed to evaluate the efficacy and safety of prescribed drug holidays of duvelisib treatment in subjects with R/R iNHL who have received at least 1 prior systemic therapy.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 102
-
Age ≥ 18 years, ECOG performance status ≤ 2
-
Histologically confirmed diagnosis of iNHL (Subtypes include FL Grades 1 to 3a, marginal zone lymphoma (splenic, nodal, or extranodal), or SLL
-
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 cm (which has not been previously irradiated), according to 2007 revised IWG 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 (ANC) ≥ 1.0 × 10^9/L
- Platelet count ≥ 75 × 10^9/L
- Hemoglobin ≥ 8 g/dL
- Estimated creatinine clearance ≥ 60 mL/min, as determined by the Cockcroft-Gault method
- Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (exception: subjects with Gilbert's Syndrome may have a bilirubin > 1.5 × ULN)
- Aspartate transaminase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum pyruvic transaminase (SGPT) ≤ 3.0 × ULN
- 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 CLL
- Prior allogeneic hematopoietic stem cell transplant (HSCT); prior treatment with a PI3K inhibitor
- History of drug-induced colitis or pneumonitis; TB 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 (CMV) or Epstein-Barr virus (EBV) infection
- Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), or herpes zoster (VZV) at screening
- Concurrent administration of medications or foods that are strong inhibitors or inducers of cytochrome P450 3A (CYP3A). No prior use within 2 weeks before the start of study intervention.
- Baseline QTcF > 500 ms
- Concurrent active malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix, bladder cancer, or prostate cancer not requiring treatment. Subjects 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 subject's risk to participating in this study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Duvelisib, Continuous and Intermittent Dosing Duvelisib Duvelisib 25 milligrams (mg) twice daily (BID) continuously for 10 weeks, followed by 25 mg BID dosed 2 weeks off and 2 weeks on for each subsequent 4-week cycle. Duvelisib, Intermittent Dosing Duvelisib Duvelisib 25 mg BID dosed 2 weeks on and 2 weeks off.
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) According to the 2007 Revised International Working Group (IWG) Criteria Up to 14 months ORR was defined as the percentage of participants achieving a complete response (CR) or partial response (PR) and assessed using the 2007 revised IWG criteria. The 2007 revised IWG criteria defined CR as the disappearance of all evidence of disease and PR as the regression of measurable disease and no new sites.
- Secondary Outcome Measures
Name Time Method Progression-free Survival (PFS) Up to 2 years PFS was defined as the time from first dose to first progressive disease (PD) or death (progression date/death date - treatment start date + 1) or, for participants without PD or documented death, as the time from first dose to censoring date (censoring date - treatment start date + 1). The 2007 revised IWG criteria defined PD as any new lesion or increase by ≥50% of previously involved sites from nadir. The 2014 Lugano criteria defined PD as a progressive metabolic response (according to positron emission tomography-computed tomography \[PET-CT\]) and progressive disease (according to computed tomography \[CT\]). Results reported as months.
ORR At Specific Timepoints 6, 12, 18, and 24 months after first dose of study intervention ORR at 6, 12, 18, and 24 months after first dose of study intervention was defined as the percentage of participants achieving CR or PR at each timepoint and was assessed using both the 2007 revised IWG criteria and the 2014 Lugano criteria. The 2007 revised IWG criteria defined CR as the disappearance of all evidence of disease and PR as the regression of measurable disease and no new sites. The 2014 Lugano criteria defined CR as a complete metabolic response (according to PET-CT) and a complete radiologic response (according to CT) and PR as partial metabolic response (according to PET-CT) and partial remission (according to CT). The response was cumulative for each timepoint; a participant was considered a responder if their first response occurred up to the end of that timepoint.
Duration of Response (DOR) Up to 2 years DOR was defined for participants with CR or PR as the time from the date of first documentation of response (CR or PR) to date of the first documentation of PD or death. The 2007 revised IWG criteria defined CR as the disappearance of all evidence of disease, PR as the regression of measurable disease and no new sites, and PD as any new lesion or increase by ≥50% of previously involved sites from nadir. The 2014 Lugano criteria defined CR as a complete metabolic response (according to PET-CT) and a complete radiologic response (according to CT), PR as partial metabolic response (according to PET-CT) and partial remission (according to CT), and PD as a progressive metabolic response (according to PET-CT) and progressive disease (according to CT). Results are reported as months.
Overall Survival (OS) Up to 2 years OS was the time from first dose to death (death date - treatment start date + 1). Participants without documented death were censored at their last known alive date (last known alive date - treatment start date + 1). Results reported as months.
Lymph Node Response Rate (LNRR) 14 months LNRR was calculated as the percentage of participants achieving ≥50% decrease in the sum of the product of the diameters of target lymph nodes. The confidence interval for LNRR was calculated only for participants who had at least 1 nodal target lesion, using the Clopper-Pearson exact method for binomial proportions. Participants whose target lesions were all extranodal were excluded from this analysis.
Time To First Response (TTFR) Up to 14 months For participants with CR or PR, TTFR was defined as the time from first dose of study intervention to time of first CR or PR and was calculated as: the date of first CR or PR - randomization date + 1. The 2007 revised IWG criteria defined CR as the disappearance of all evidence of disease and PR as the regression of measurable disease and no new sites. The 2014 Lugano criteria defined CR as a complete metabolic response (according to PET-CT) and a complete radiologic response (according to CT) and PR as partial metabolic response (according to PET-CT) and partial remission (according to CT). Results are reported as months.
Time To Treatment Failure (TTF) Up to 2 years TTF was calculated as the time from first dose of study treatment to discontinuation for any reason (discontinuation date - treatment start date + 1). Participants who were still ongoing treatment at time of data cut were censored (last dose date - treatment start date + 1). Results reported as months.
ORR According to 2014 Lugano Criteria Up to 14 months ORR was defined as the percentage of participants achieving a CR or PR and was assessed using the 2014 Lugano criteria. The 2014 Lugano criteria defined CR as a complete metabolic response (according to PET-CT) and a complete radiologic response (according to CT) and PR as partial metabolic response (according to PET-CT) and partial remission (according to CT).
Trial Locations
- Locations (28)
Pratia Onkologia Katowice
🇵🇱Katowice, Poland
Ospedale di Circolo, PO Varese, AO Ospedale di Circolo e Fondazione Macchi
🇮🇹Varese, Italy
Universitaetsklinikum Bonn AöR
🇩🇪Bonn, Germany
Asan Medical Center - Oncology
🇰🇷Seoul, Korea, Republic of
AUSL di Reggio Emilia IRCCS, Arcispedale Santa Maria Nuova di Reggio Emilia
🇮🇹Reggio Emilia, Italy
State Budgetary Healthcare Institution of Moscow City Moscow Multidisciplinary Clinical Center "Kommunarka" of the Department of Healthcare of Moscow City
🇷🇺Moscow, Russian Federation
Samsung Medical Center - Hematology-Oncology
🇰🇷Seoul, Korea, Republic of
Mid-Florida Cancer Centers
🇺🇸Orange City, Florida, United States
City Clinical Hospital n.a. Botkin
🇷🇺Moscow, Russian Federation
FN Hradec Kralove
🇨🇿Hradec Králové, Czechia
Christie Hospital NHS Foundation Trust
🇬🇧Manchester, United Kingdom
First Saint-Petersburg State Medical University n.a. I.P. Pavlov
🇷🇺Sankt-Peterburg, Russian Federation
NHS Greater Glasgow & Clyde - CRUK Clinical Trials Unit
🇬🇧Glasgow, United Kingdom
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o.
🇵🇱Slupsk, Pomorskie, Poland
Vseobecna fakultni nemocnice v Praze
🇨🇿Praha 2, Czechia
Centrum Medyczne Pratia Poznan
🇵🇱Skórzewo, Poland
Royal Liverpool Hospital [Hematology/Transfusion Medicine]
🇬🇧Liverpool, United Kingdom
IEO - Istituto Europeo di Oncologia, IRCCS
🇮🇹Milano, Italy
Florida Cancer Specialists - Fort Myers
🇺🇸Fort Myers, Florida, United States
Florida Cancer Specialists & Research Institute - Lecanto
🇺🇸Lecanto, Florida, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Robert H. Lurie Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Oncology Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori
🇮🇹Meldola, Forli, Italy
Azienda Ospedaliera Santa Maria di Terni
🇮🇹Terni, Italy
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of