A Phase 3 (extension) clinical trial to examine the efficacy of IPI-145 (duvelisib) monotherapy or ofatumumab monotherapy in participants with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who experienced disease progression after treatment with IPI-145 or ofatumumab in study IPI-145-07 (NCT02004522).
The study was designed as an open-label, two-arm extension evaluation to enable participants who experienced radiologically confirmed disease progression in study IPI-145-07 to receive the alternative treatment (either IPI-145 or ofatumumab) other than what was received during study IPI-145-07. Participants who previously had received ofatumumab in study IPI-145-07 received a starting dose of 25 milligrams (mg) IPI-145 twice daily continuously in a 21-day cycle for Cycle 1, followed by 28-day treatment cycles thereafter for up to 11 cycles or until disease progression, discontinuation from study participation, or start of subsequent therapy, whichever occurred first. After completing approximately 11 cycles of treatment with duvelisib, participants who, in the judgment of the investigator, may have derived benefit from continued treatment may have continued to receive additional cycles of duvelisib until disease progression or unacceptable toxicity. However, to receive additional cycles of duvelisib beyond 11 cycles, participants must have had evidence of response and CLL/SLL requiring treatment according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL)/International Working Group by Cycle 12 Day 1. Participants who previously received IPI-145 in study IPI-145-07 received treatment consistent approved product labeling which consisted of a starting dose of 300 mg ofatumumab on Day 1, followed by seven weekly doses of 2000 mg. Thereafter, participants received 2000 mg ofatumumab once every month for four months unless disease progression or unacceptable toxicity occurred. Administration of ofatumumab was not to exceed the 12 doses (within 7 cycles).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
99
PI3K Inhibitor
Monoclonal antibody
Overall Response Rate (ORR)
ORR was defined as the percentage of participants with a best response (per investigator assessment) of complete response (CR), CR with incomplete marrow recovery (CRi), partial response (PR), or PR with lymphocytosis (PRwL), according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) or revised International Working Group Response (IWG) Criteria, with modification for treatment-related lymphocytosis. The 95% confidence interval was calculated using exact binomial method. Select IWCLL criteria for tumor load assessed by computed tomography (CT): CR/CRi (CLL only), lymphadenopathy (none \>1.5 centimeters \[cm\]), hepatomegaly/splenomegaly (none); PR, lymphadenopathy/hepatomegaly/splenomegaly (decrease ≥50%); PRwL, lymphadenopathy only (decrease ≥50%). Select IWG criteria for tumor load assessed by CT: CR, lymphadenopathy/hepatomegaly/splenomegaly (normal size); PR, lymphadenopathy/hepatomegaly/splenomegaly (decrease ≥50%); PRwL, lymphadenopathy only (decrease ≥50%).
Time frame: Until progressive disease (PD), death, or other anticancer therapy is initiated (up to 4.5 years)
Duration of Response (DOR)
DOR was defined as the time from the first documentation of response per investigator assessment to either PD or death due to any cause. DOR was evaluated using the Kaplan-Meier method based on all treated participants with a documentation of response (that is, CR, CRi, PR, or PRwL) as determined by investigator assessment. Select IWCLL criteria for tumor load assessed by CT: CR/CRi (CLL only), lymphadenopathy (none \>1.5 cm), hepatomegaly/splenomegaly (none); PR, lymphadenopathy/hepatomegaly/splenomegaly (decrease ≥50%); PRwL, lymphadenopathy only (decrease ≥50%). Select IWG criteria for tumor load assessed by CT: CR, lymphadenopathy/hepatomegaly/splenomegaly (normal size); PR, lymphadenopathy/hepatomegaly/splenomegaly (decrease ≥50%); PRwL, lymphadenopathy only (decrease ≥50%).
Time frame: From the first documentation of response to the first documentation of PD or death due to any cause (up to 4.5 years)
Progression-free Survival (PFS)
PFS was defined as the time from the first dose of study treatment to the first documentation of either investigator-assessed PD or death resulting from any cause. PFS was determined using the Kaplan-Meier method based on all treated participants with a documentation of response (that is, CR, CRi, PR, or PRwL) as determined by investigator assessment.
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Unnamed facility
La Jolla, California, United States
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Denver, Colorado, United States
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Fort Myers, Florida, United States
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St. Petersburg, Florida, United States
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Boston, Massachusetts, United States
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Boston, Massachusetts, United States
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St Louis, Missouri, United States
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Hackensack, New Jersey, United States
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New Brunswick, New Jersey, United States
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New York, New York, United States
...and 59 more locations
Time frame: From the first dose of study treatment to the first documentation of PD or death from any cause (up to 4.5 years)