A Phase 2 Study Comparing 2 Intermittent Dosing Schedules of Duvelisib in Participants With Indolent Non-Hodgkin Lymphoma

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

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.