[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100658118":3},{"organization":4,"outcomesModule":7,"designInfo":48,"detailedDescription":54,"studyPopulation":47,"armGroups":55,"interventions":64,"overallOfficials":80,"centralContacts":84,"locations":90,"responsibleParty":121,"collaborators":124,"id":128,"slug":129,"hasResults":130,"nctId":131,"briefTitle":132,"officialTitle":133,"acronym":47,"eligibilityCriteria":134,"healthyVolunteers":130,"sex":135,"minAge":136,"maxAge":47,"enrollmentInfo":137,"targetDuration":47,"studyType":140,"phases":141,"briefSummary":144,"conditions":145,"keywords":148,"overallStatus":150,"whyStopped":47,"lastUpdateSubmitDate":151,"lastUpdatePostDateStruct":152,"startDateStruct":155,"completionDateStruct":157,"leadSponsor":159,"locationsCount":160},{"fullName":5,"class":6},"Dana-Farber Cancer Institute","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":47},[9],{"measure":10,"description":11,"timeFrame":12},"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",[14,18,22,25,29,33,37,40,43],{"measure":15,"description":16,"timeFrame":17},"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).","At the end of 1 year of combination therapy.",{"measure":19,"description":20,"timeFrame":21},"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.","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.",{"measure":23,"description":24,"timeFrame":21},"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.",{"measure":26,"description":27,"timeFrame":28},"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.","At the end of treatment (up to 18 months).",{"measure":30,"description":31,"timeFrame":32},"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.","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).",{"measure":34,"description":35,"timeFrame":36},"ORR [Phase II]","ORR is defined as the proportion of participants who achieve a CR, CRi, nPR, or PR according to 2018 iwCLL criteria.","Assessed at baseline and on Day 1 of Cycle 2 and subsequent cycles (each cycle is 28 days), up to 18 months.",{"measure":38,"description":39,"timeFrame":36},"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.",{"measure":41,"description":42,"timeFrame":32},"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.",{"measure":44,"description":45,"timeFrame":46},"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.","Assessed every 2 months for 3 years and every 4 months for an additional 2 years after completion of the 18-month treatment period.",null,{"allocation":49,"interventionModel":50,"interventionModelDescription":47,"primaryPurpose":51,"observationalModel":47,"timePerspective":47,"maskingInfo":52},"NA","SINGLE_GROUP","TREATMENT",{"masking":53,"maskingDescription":47,"whoMasked":47},"NONE","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.\n\nPhase 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.\n\nAll 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.\n\nUp to 40 patients will be enrolled over 36 months.",[56],{"label":57,"type":58,"description":59,"interventionNames":60},"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.",[61,62,63],"Drug: Roginolisib","Drug: Obinutuzumab","Drug: Venetoclax",[65,72,76],{"type":66,"name":67,"description":68,"armGroupLabels":69,"otherNames":70},"DRUG","Roginolisib","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\u002Ftoxicity.",[57],[71],"IOA-244",{"type":66,"name":73,"description":74,"armGroupLabels":75,"otherNames":47},"Obinutuzumab","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.",[57],{"type":66,"name":77,"description":78,"armGroupLabels":79,"otherNames":47},"Venetoclax","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.",[57],[81],{"name":82,"affiliation":5,"role":83},"Jennifer Brown, MD, PhD","PRINCIPAL_INVESTIGATOR",[85],{"name":86,"role":87,"phone":88,"phoneExt":47,"email":89},"Hang Phan","CONTACT","857-215-1258","hang_phan@dfci.harvard.edu",[91,112],{"facility":92,"status":47,"city":93,"state":94,"zip":95,"country":96,"countryCode":97,"cosmosGeoPoint":98,"geoPoint":103,"contacts":104},"Brigham and Women's Hospital","Boston","Massachusetts","02214","United States","US",{"type":99,"coordinates":100},"Point",[101,102],-71.05977,42.35843,{"lat":102,"lon":101},[105,109,111],{"name":106,"role":87,"phone":107,"phoneExt":47,"email":108},"Jennier Brown, MD, PhD","617-632-4564","jennifer_brown@dfci.harvard.edu",{"name":110,"role":87,"phone":107,"phoneExt":47,"email":108},"MD, PhD",{"name":82,"role":83,"phone":47,"phoneExt":47,"email":47},{"facility":113,"status":47,"city":93,"state":94,"zip":114,"country":96,"countryCode":97,"cosmosGeoPoint":115,"geoPoint":117,"contacts":118},"Dana Farber Cancer Institute","02215",{"type":99,"coordinates":116},[101,102],{"lat":102,"lon":101},[119,120],{"name":82,"role":87,"phone":107,"phoneExt":47,"email":108},{"name":82,"role":83,"phone":47,"phoneExt":47,"email":47},{"type":83,"investigatorFullName":122,"investigatorTitle":123,"investigatorAffiliation":5,"oldNameTitle":47,"oldOrganization":47},"Jennifer R. Brown, MD, PhD","Principal Investigator",[125],{"name":126,"class":127},"iOnctura","INDUSTRY","100658118","phase-1-roginolisib-plus-obinutuzumab--venetoclax-in-rr-cll-100658118",false,"NCT07847957","Roginolisib Plus Obinutuzumab + Venetoclax in R\u002FR CLL","A Phase 1b and 2 Study of Roginolisib (IOA-244) Combined With Obinutuzumab Followed by Venetoclax in Patients With Refractory\u002FRelapsed Chronic Lymphocytic Leukemia (CLL) After Progression on Prior Bruton Tyrosine Kinase (BTK) Inhibitors","Inclusion Criteria:\n\n* Participants with relapsed\u002Frefractory CLL who meet iwCLL criteria for requiring treatment (Hallek et al. 2018).\n* Participants with measurable disease as defined by at least one of: circulating lymphocytosis \\> 5000 B cells\u002Fmicroliter, 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)\n* Participants must have received at least one prior therapy for CLL including systemic therapy containing a covalent BTK inhibitor.\n* Participants willing to undergo a pre-treatment and on treatment bone marrow biopsy.\n\nAge ≥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 \\\u003C18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.\n\nEastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.\n\n-Participants must meet the following organ and marrow function as defined below:\n\n* Platelet count ≥50 x 109\u002FL\\^\\^\\^\n* Total bilirubin ≤ 1.5 ×institutional upper limit of normal (ULN)\\*\n* AST(SGOT)\u002FALT(SGPT) ≤3.0 × institutional ULN\n* Creatinine clearance ≥ 50 mL\u002Fmin\\*\\* Thrombocytopenia due to marrow involvement of CLL: \\> 30 x 109\u002FL\n\n  * unless increase attributed to leukemic organ involvement, hemolysis or Gilbert's syndrome. Participants who are \\\u003C 75 years may have bilirubin of ≤ 3.0 × ULN \\*\\* calculated by the Cockcroft Gault formula or measured by 24 hours urine collection\n\nParticipants 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.\n\nWillingness to undergo a pre-treatment and on-treatment bone marrow biopsy to evaluate MRD.\n\nWillingness to use adequate contraception prior to study entry and for the duration of study participation.\n\n* The effects of roginolisib on the developing human fetus are unknown.\n* 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.\n* 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.\n\nAbility to understand and the willingness to sign a written informed consent document, which includes compliance with the requirements of this protocol.\n\nEligible to receive infection prophylaxis and supportive care as per institutional guidelines.\n\nExclusion Criteria:\n\n* 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.\n\nParticipants 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\n\n-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\u002FdL or platelets \\> 10,000 mL without transfusion support.\n\nHistory 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).\n\n* 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.\n* 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.\n* 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.\n\nBecause 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)\n\nAs part of the enrollment\u002Finformed 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.\n\nPregnant 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.\n\nParticipants 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:\n\n* Malignancies surgically treated with curative intent and with no known active disease present\n* Adequately treated nonmelanoma skin cancer or lentigo maligna without evidence of disease\n* Adequately treated cervical carcinoma in situ without evidence of disease.\n* Surgically\u002Fadequately treated low-grade, early-stage, localized prostate cancer without evidence of disease or low risk localized prostate cancer on observation.\n* Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications.\n* History or presence of cardiovascular disease, which in the Investigator's opinion may impact the clinical trial participation.\n* History of tuberculosis treatment within the preceding two years.\n\nOngoing 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\u002Fexclusion 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.\n\nKnown 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.\n\nAny 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.\n\nKnown alcohol or substance abuse.","ALL","18 Years",{"count":138,"type":139},40,"ESTIMATED","INTERVENTIONAL",[142,143],"PHASE1","PHASE2","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.",[146,147],"Chronic Lymphocytic Leukemia (CLL)","Refractory Chronic Lymphocytic Leukemia",[146,149],"Relapsed\u002FRefractory CLL","NOT_YET_RECRUITING","2026-09-28",{"date":153,"type":154},"2026-09-29","ACTUAL",{"date":156,"type":139},"2027-01-13",{"date":158,"type":139},"2027-04-01",{"name":5,"class":6},2]