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Chronic Lymphocytic Leukemia (CLL)Phase 1/2NCT07847957

Roginolisib Plus Obinutuzumab + Venetoclax in R/R CLL

A Phase 1/2 study testing Roginolisib, Obinutuzumab and Venetoclax in people with Chronic Lymphocytic Leukemia (CLL) and Refractory Chronic Lymphocytic Leukemia, run by Dana-Farber Cancer Institute at 2 sites in United States.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Roginolisib, Obinutuzumab and Venetoclax
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
2 sitesUnited States
Study dates
13 Jan 2027to 1 Apr 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • -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.
  • The effects of roginolisib on the developing human fetus are unknown.
  • Venetoclax may cause embryo fetal harm when administered to pregnant women. Anti-CD20 targeting agents are likely to cause fetal B-cell depletion. For this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Women of child-bearing potential will be required to have a negative serum pregnancy test during screening and a negative serum pregnancy test on Cycle 1 Day 1. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of roginolisib or venetoclax administration. Contraception must be conducted up to 12 months after taking the last rituximab dose.
  • Ability to understand and the willingness to sign a written informed consent document, which includes compliance with the requirements of this protocol.
  • Eligible to receive infection prophylaxis and supportive care as per institutional guidelines.

Who cannot join

  • 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.
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  • 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.
  • Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications.
  • History or presence of cardiovascular disease, which in the Investigator's opinion may impact the clinical trial participation.
  • History of tuberculosis treatment within the preceding two years.
  • Ongoing systemic bacterial, fungal, or viral infections (including also hepatitis viral infection) at the time of initiation of study treatment (defined as requiring intravenous [IV] antimicrobial, antifungal or antiviral agents). Subjects on antimicrobial, antifungal or antiviral prophylaxis are not specifically excluded if all other inclusion/exclusion criteria are met, there is no evidence of active infection at enrollment, and ongoing treatment does not have a significant risk of drug-drug interaction with venetoclax.
  • Known Human immunodeficiency virus (HIV) infection which is treated with agents that can interfere with venetoclax due to potential drug-drug interactions or increased risk of myelotoxicity.
  • Any serious or uncontrolled medical disorder or active infection that, in the opinion of the Investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the participant to receive protocol therapy.
  • Known alcohol or substance abuse.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Hang Phan contact

857-215-1258

hang_phan@dfci.harvard.edu

United States2 sites

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02214

    Jennier Brown, MD, PhD, 617-632-4564, jennifer_brown@dfci.harvard.edu

    MD, PhD, 617-632-4564, jennifer_brown@dfci.harvard.edu

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

    Jennifer Brown, MD, PhD, 617-632-4564, jennifer_brown@dfci.harvard.edu

    Jennifer Brown, MD, PhD

Other trials in United States

About this study

Official title: A Phase 1b and 2 Study of Roginolisib (IOA-244) Combined With Obinutuzumab Followed by Venetoclax in Patients With Refractory/Relapsed Chronic Lymphocytic Leukemia (CLL) After Progression on Prior Bruton Tyrosine Kinase (BTK) Inhibitors

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.

Read the detailed description

The study consists of two parts: Phase 1b: A safety lead-in using a 3+3 dose escalation design to determine the recommended dose of roginolisib (40 mg or 80 mg QD) in combination with obinutuzumab. After 6 months of combination therapy, venetoclax is added for 6-12 months. DLTs are assessed at the end of cycle 2.

Phase 2: Dose expansion at the recommended phase 2 dose. Participants receive obinutuzumab and roginolisib for 6 months, followed by venetoclax and roginolisib for an additional 6 months. Participants who do not achieve uMRD after 12 months may continue therapy for another 6 months.

All participants will receive roginolisib orally once daily, obinutuzumab intravenously as per label for 6 cycles, and venetoclax orally as per label starting at cycle 7 with standard ramp-up. The primary endpoint is the rate of objective response with uMRD in bone marrow at the end of one year of combination therapy.

Up to 40 patients will be enrolled over 36 months.

Being tested
Roginolisib, Obinutuzumab, Venetoclax
Keywords
Chronic Lymphocytic Leukemia (CLL), Relapsed/Refractory CLL
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RoginolisibDrug

    Also called IOA-244

    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.

  • ObinutuzumabDrug

    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.

  • VenetoclaxDrug

    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.

Study groups in NCT07847957
Study groupRoleWhat they receive
Roginolisib + Obinutuzumab followed by Roginolisib + VenetoclaxExperimentalAll 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.
Receives: Drug: Roginolisib; Drug: Obinutuzumab; Drug: Venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 2 months

Secondary outcomes (9)

  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).

    Measured: 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.

    Measured: 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.

    Measured: 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.

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

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

    PFS based on Kaplan-Meier method is defined as the time from study registration to disease progression (PD) or death from any cause, whichever occurs first. Participants without documented disease progression or death will be censored at the date of their last disease assessment. PD according to 2018 iwCLL criteria is defined as the appearance of new disease sites, a ≥50% increase in previously involved disease sites or circulating lymphocyte count, Richter transformation, or development of CLL-related neutropenia, anemia, or thrombocytopenia.

    Measured: 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).

  6. ORR [Phase II]

    ORR is defined as the proportion of participants who achieve a CR, CRi, nPR, or PR according to 2018 iwCLL criteria.

    Measured: Assessed at baseline and on Day 1 of Cycle 2 and subsequent cycles (each cycle is 28 days), up to 18 months.

  7. Complete Response Rate (CRR) [Phase II]

    CRR is defined as the proportion of participants who achieve a CR or CRi during treatment according to 2018 iwCLL criteria.

    Measured: Assessed at baseline and on Day 1 of Cycle 2 and subsequent cycles (each cycle is 28 days), up to 18 months.

  8. Duration of Remission (DOR) [Phase II]

    DOR based on Kaplan-Meier method is defined as the time from first achivement of CR, Cri, nPR, or PR to PD according to 2018 iwCLL criteria. PD is defined as the appearance of new disease sites, a ≥50% increase in previously involved disease sites or circulating lymphocyte count, Richter transformation, or development of CLL-related neutropenia, anemia, or thrombocytopenia.

    Measured: 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).

  9. Median Overall Survival (OS) [Phase II]

    OS based on Kaplan-Meier method is defined as the time from study registration to death from any cause. Participants who are alive at the time of analysis will be censored at the date they were last known to be alive.

    Measured: Assessed every 2 months for 3 years and every 4 months for an additional 2 years after completion of the 18-month treatment period.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Sep 2026
  2. Study start13 Jan 2027 (estimated)
  3. Primary completion1 Apr 2027 (estimated)
  4. Study completion1 Apr 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07847957
Sponsor's protocol ID
26-138
Status last verified
Sep 2026
First submitted
10 Aug 2026
Last updated
29 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Harvard Cancer Consortium encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Roginolisib, Obinutuzumab and Venetoclax in people with Chronic Lymphocytic Leukemia (CLL) and Refractory Chronic Lymphocytic Leukemia, run by Dana-Farber Cancer Institute at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 29 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Hang Phan (857-215-1258, hang_phan@dfci.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Experiencing Dose-Limiting Toxicities (DLT) [Phase Ib] (time frame: Up to 2 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07847957.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2026.

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