Roginolisib Plus Obinutuzumab + Venetoclax in R/R CLL
Trial statusNot yet recruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorDana-Farber Cancer Institute
About this trial
This is a Phase 1b and 2, open-label, single-arm study evaluating the safety, tolerability, and efficacy of roginolisib (IOA-244) in combination with obinutuzumab followed by venetoclax in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) who have progressed after prior Bruton Tyrosine Kinase (BTK) inhibitor therapy. The study aims to determine the maximum tolerated dose of roginolisib in combination with obinutuzumab, and to assess the rate of undetectable minimal residual disease (uMRD) after sequential therapy with roginolisib, obinutuzumab, and venetoclax.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Participants with relapsed/refractory CLL who meet iwCLL criteria for requiring treatment (Hallek et al. 2018).
Participants with measurable disease as defined by at least one of: circulating lymphocytosis > 5000 B cells/microliter, bone marrow involvement > 30%, palpable splenomegaly or lymph nodes > 1.5 cm. Computer tomography (CT) at screening must be performed and followed every 2 cycles (1 cycle = 28 days)
Participants must have received at least one prior therapy for CLL including systemic therapy containing a covalent BTK inhibitor.
Participants willing to undergo a pre-treatment and on treatment bone marrow biopsy.
Disqualifiers
Participants who have received prior treatment with venetoclax or PI3K inhibitors in the last 6 months. Participants must not have had any CLL-directed anticancer therapy within 5 half-lives of the therapy prior to Cycle 1 Day 1.
Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1) with the exception of alopecia or fatigue. Any irAEs from prior immunotherapy must have complete resolution and must have resolved at least 2 weeks before Cycle1 Day1.
Participants who are receiving any other investigational agents for this condition History of allergic reactions attributed to compounds of similar chemical or biologic composition to roginolisib or venetoclax or their formulation components or prior anti-CD20 targeting agents more than 6 months before initiating study treatments.
Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A are ineligible. Moderate CYP3A inhibitors and P-gp inhibitors can be administered when venetoclax dose is reduced to 50%. Otherwise, venetoclax is contraindicated in participants requiring strong or moderate CYP3A inducers.
Trial design
Design model
Single group
Treatments tested in this trial
Roginolisib
DrugOral, once daily, 40 mg or 80 mg QD depending on cohort, starting on day 1 of cycle 1 and continuing until cycle 13 or until progression/toxicity.
Obinutuzumab
DrugIntravenous infusion, administered as per label for 6 cycles (28-day cycles): 100 mg on day 1 cycle 1, 900 mg on day 2 cycle 1, 1000 mg on days 8 and 15 of cycle 1, then 1000 mg on day 1 of cycles 2-6.
Venetoclax
DrugOral, once daily, starting at cycle 7 with standard weekly dose escalation (20 mg, 50 mg, 100 mg, 200 mg, 400 mg), then continued for 6-12 months depending on MRD results.
Treatment groups
40 Participants
are divided into 1 treatment groupGroup A: Roginolisib + Obinutuzumab followed by Roginolisib + VenetoclaxExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
Number of Participants Experiencing Dose-Limiting Toxicities (DLT) [Phase Ib]
DLT is defined according to NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0, including grade 4 neutropenia lasting \>7 days, febrile neutropenia, grade ≥3 thrombocytopenia with clinically significant bleeding, grade ≥4 infection, grade ≥3 non-hematologic toxicity (with protocol-specified exceptions), grade ≥3 diarrhea, severe cutaneous reactions (grade ≥3), significant hepatic toxicity, inability to initiate Cycle 2 within 14 days due to treatment-related toxicity, and grade 5 adverse events not clearly attributable to the underlying disease.
Time frame
Up to 2 monthsSecondary outcomes
1
Objective Response Rate (ORR) With Undetectable Minimal Residual Disease (uMRD) [Phase II]
ORR with uMRD is defined as the proportion of participants who achieve a complete response (CR), complete response with incomplete marrow recovery (CRi), nodular partial response (nPR), or partial response (PR) according to 2018 iwCLL criteria and undetectable minimal residual disease (uMRD), defined as fewer than 1 CLL cell per 10,000 leukocytes in bone marrow as assessed by clonoSEQ (10-⁴ sensitivity).
Time frame
At the end of 1 year of combination therapy.2
Non-hematologic Toxicity Rate [Phase II]
Non-hematologic toxicity rate is defined as the proportion of participants experiencing non-hematologic toxicities graded according to NCI CTCAE version 5.0.
Time frame
Up to 18 months. Adverse events are assessed on Days 1, 2, 8, and 15 of Cycles 1 and 7 and on Day 1 of all other cycles; each cycle is 28 days.3
Hematologic Toxicity Rate [Phase II]
Hematologic toxicity rate is defined as the proportion of participants experiencing hematologic toxicities according to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria.
Time frame
Up to 18 months. Adverse events are assessed on Days 1, 2, 8, and 15 of Cycles 1 and 7 and on Day 1 of all other cycles; each cycle is 28 days.4
uMRD Rate [Phase II]
uMRD rate is defined as the proportion of participants with undetectable minimal residual disease, defined as fewer than 1 CLL cell per 10,000 leukocytes, in peripheral blood and bone marrow as assessed by flow cytometry.
Time frame
At the end of treatment (up to 18 months).Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Dana-Farber Cancer Institute
Lead sponsor
iOnctura
Collaborator
Source ClinicalTrials.gov
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