Roginolisib Plus Obinutuzumab + Venetoclax in R/R CLL

NCT07847957 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 26-138
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Chronic Lymphocytic Leukemia (CLL); Refractory Chronic Lymphocytic Leukemia

Keywords

Chronic Lymphocytic Leukemia (CLL); Relapsed/Refractory CLL

Outcome Measures

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.

  Up to 2 months

Secondary Outcomes (9)

• Objective Response Rate (ORR) With Undetectable Minimal Residual Disease (uMRD) [Phase II]

  At the end of 1 year of combination therapy.

• Non-hematologic Toxicity Rate [Phase II]

  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.

• Hematologic Toxicity Rate [Phase II]

  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.

• uMRD Rate [Phase II]

  At the end of treatment (up to 18 months).

• Median Progression-Free Survival (PFS) [Phase II]

  Assessed at baseline and on Day 1 of Cycle 2 and subsequent cycles (each cycle is 28 days) during treatment (up to 18 months). Assessments will then performed every 2 months for 3 years and every 4 months for an additional 2 years (total of 5 years).

Study Arms (1)

Roginolisib + Obinutuzumab followed by Roginolisib + Venetoclax

EXPERIMENTAL

All participants receive roginolisib orally once daily in the morning, obinutuzumab intravenously as per label for 6 cycles, and venetoclax orally as per label starting at cycle 7 with standard ramp-up.

Drug: Roginolisib; Drug: Obinutuzumab; Drug: Venetoclax

Interventions

Roginolisib DRUG

Oral, 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.

Also known as: IOA-244

Roginolisib + Obinutuzumab followed by Roginolisib + Venetoclax

Obinutuzumab DRUG

Intravenous 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.

Roginolisib + Obinutuzumab followed by Roginolisib + Venetoclax

Venetoclax DRUG

Oral, 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.

Roginolisib + Obinutuzumab followed by Roginolisib + Venetoclax

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age ≥18 years, at the time of signing the IRB approved informed consent. Because no dosing or adverse event data are currently available on the use of venetoclax in combination with roginolisib in participants \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• Participants must meet the following organ and marrow function as defined below:
• Platelet count ≥50 x 109/L\^\^\^
• Total bilirubin ≤ 1.5 ×institutional upper limit of normal (ULN)\*
• AST(SGOT)/ALT(SGPT) ≤3.0 × institutional ULN
• Creatinine clearance ≥ 50 mL/min\*\* Thrombocytopenia due to marrow involvement of CLL: \> 30 x 109/L
• unless increase attributed to leukemic organ involvement, hemolysis or Gilbert's syndrome. Participants who are \< 75 years may have bilirubin of ≤ 3.0 × ULN \*\* calculated by the Cockcroft Gault formula or measured by 24 hours urine collection
• Participants with clinically inactive CNS disease or treated CNS disease that is no longer symptomatic, or who need corticosteroids or anticonvulsants may be enrolled in the study. For participants who have symptoms present, imaging and lumbar puncture must be performed to exclude a CNS condition that may impact the study conduct.
• Willingness to undergo a pre-treatment and on-treatment bone marrow biopsy to evaluate MRD.
• Willingness to use adequate contraception prior to study entry and for the duration of study participation.

You may not qualify if:

• 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 received a live vaccine within 30 days of planned start of study therapy. With regards to other type of vaccines, including SARS-Co2 vaccines, these are allowed
• Participants requiring ongoing treatment with chronic high dose immunosuppressants (e.g., cyclosporine) or systemic steroids \> 20 mg prednisone (or equivalent) QD. For example, participants with uncontrolled autoimmune haemolytic anaemia (AIHA) or idiopathic thrombocytopenia purpura (ITP), which requires \> 20 mg once daily (QD) of prednisone (or equivalent) to maintain haemoglobin levels of \>8.0 g/dL or platelets \> 10,000 mL without transfusion support.
• History of transformation of CLL to aggressive non-Hodgkin lymphoma (Richter´s transformation or pro-lymphocytic leukaemia) which may otherwise interfere with the interpretation of the outcome of the study (including biomarker evaluation).
• 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.
• Because of ongoing research, regularly consulting medical reference databases is recommended. One such reference is the Website of the US-FDA: (Drug Interactions \| Relevant Regulatory Guidance and Policy Documents \| FDA)
• As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
• Pregnant women are excluded from this study because venetoclax has the potential to cause embryo-fetal harm, and the potential for teratogenic or abortifacient effects with roginolisib is currently unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with roginolisib or venetoclax breastfeeding should be discontinued if the mother is treated with these agents.
• Participants with a history of other primary malignancy are excluded when they require therapy that will interfere with the investigational treatments. Exceptions are if the natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen. For example:
• Malignancies surgically treated with curative intent and with no known active disease present
• Adequately treated nonmelanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated cervical carcinoma in situ without evidence of disease.
• Surgically/adequately treated low-grade, early-stage, localized prostate cancer without evidence of disease or low risk localized prostate cancer on observation.

Sponsors & Collaborators

• iOnctura: collaborator
• Dana-Farber Cancer Institute: lead

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02214, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Recurrence

Interventions

obinutuzumab; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jennifer Brown, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hang Phan

CONTACT

857-215-1258; hang_phan@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 10, 2026
• First Posted: September 29, 2026
• Study Start (Estimated): January 13, 2027
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: September 29, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer office for Dana -Farber Innovations (BODFI) at innovations@dfci.harvard.edu

Locations

US (2)