[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"replication-repair-deficient\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:replication-repair-deficient":31},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,44],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":4,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":33,"lastUpdatePostDateStruct":34,"startDateStruct":37,"completionDateStruct":39,"leadSponsor":41,"locationsCount":4},"100642450","phase-2-study-of-relatlimab-and-nivolumab-opdualag-in-replication-repair-deficient-hgg-and-dipg-100642450",false,"NCT07644312","Study of Relatlimab and Nivolumab (Opdualag) in Replication Repair Deficient HGG and DIPG","Feasibility and Phase 2a Study of Relatlimab and Nivolumab (Opdualag™) in Adolescent and Young Adult Patients Newly Diagnosed With Replication Repair Deficient High-Grade Glioma (HGG), Including Diffuse Intrinsic Pontine Glioma (DIPG)","Inclusion Criteria:\n\n* Patients must be ≥12 years and ≤39 years of age at the time of enrollment on TarGeT-SCR.\n* Within the United States, patients must weight ≥ 40 kg at the time of enrollment. For all other countries, patients must weight ≥ 30 kg at the time of enrollment.\n\nDiagnosis:\n\n* Patients with newly-diagnosed HGG, including DIPG, are eligible. All patients mut have histologic confirmation from diagnostic biopsy or resection. The diagnosis of HGG, including DIPG must have been confirmed through TarGeT-SCR.\n* All HGGs must be WHO Grade 3 or 4. Note: WHO Grade 2 gliomas with pontine epicenter and diffuse involvement of at least 2\u002F3 of the pons are eligible.\n\nDisease Status:\n\n* Patients must be newly diagnosed.\n* Measurable disease is not required.\n* Patients with primary spinal tumors are eligible.\n* Patients should have no evidence of herniation or impending herniation, and no mass effect leading to severe midline shift.\n* Patients with prior malignancy are eligible.\n* Metastatic disease is excluded.\n* Disseminated or multifocal disease: discussion with Study Chairs is required. Patients with multifocal disease who received upfront CSI are not eligible.\n\nDemonstration of DNA replication repair deficiency (RRD) by fulfilling at least 2 of the following criteria:\n\n* Tumor mutational burden greater than or equal to 5 mutations\u002Fmegabase (Intermediate and high TMB)\n* Genetic diagnosis of germline Constitutional Mismatch Repair Deficiency (CMMRD), Lynch Syndrome, or Polymerase-Proofreading Deficiency (PPD)\n* Validated functional genomic assay (e.g. LOGIC) confirming mismatch repair (MMR) deficiency\n* Immunohistochemistry (IHC) demonstrating loss of protein expression of any of the 4 MMR genes\n\nPerformance Level: Karnofsky ≥ 50 for patients \\> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age\n\nPrior Therapy for HGG:\n\n* Surgery, RT, and\u002For dexamethasone are permissible. Temozolomide administration is highly discouraged with concurrent RT, but permissible. Anti-VEGF treatment used for vasogenic edema or steroid weaning is permitted. No other prior anticancer therapy for HGG will be allowed. Anti-VEGF use is well-established to not impact outcomes in HGG and is not considered as oncologic treatment but rather as a supportive measure to minimize steroid use in this setting. Discussion with Study Chairs is highly recommended.\n* RT requirements: Patients must have received photon or proton focal RT and administered at a standard dose, including:\n* 54 Gy in 30 fractions for DIPG\n* 54-59.4 Gy in 30-33 fractions for other HGG\n* 45-54 Gy for primary spinal cord HGG Note: Variances in RT dose within 10% of standard doses listed above are acceptable.\n* Timing between diagnosis and start of RT: Patients must have started RT \\\u003C 42 calendar days from initial diagnosis.\n* Timing post-RT: The earliest patent can begin protocl treatment is 28 days post-completion of RT. It is recommended treatment should begin within 25 days, however patients must start treatment on TarGeT-F no later than 8 weeks post-completion of RT.\n\nOrgan Function Requirements:\n\n* ANC ≥ 1000\u002Fmm3\n* Platelet count ≥ 100,000\u002Fmm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n* Hemoglobin \\> 8g\u002FdL (may be transfused)\n* Creatinine clearance or radioisotope GFR≥ 70 mL\u002Fmin\u002F1.73 m2 OR serum creatinine based on age\u002Fgender as follows:\n\n  10 to \\\u003C 13 years: 1.2 mg\u002FdL for males and females 13 to \\\u003C 16 years: 1.5 mg\u002FdL for males and 1.4 mg\u002FdL for females\n  * 16 years: 1.7 mg\u002FdL for males and 1.4 mg\u002FdL for females\n* AST\u002FALT \\\u003C 3 times the ULN. For the purpose of this study, the ULN for ALT and AST is 45 U\u002FL.\n* Ejection fraction greater than or equal to 50% as measured by echocardiogram or multiple-gated acquisition\n* QTc ≤ 480 msec (by Bazett formula)\n* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled.\n* TSH within institutional guidelines for normal range.\n\nExclusion Criteria:\n\n* Pregnant or breastfeeding patients are excluded.\n* Patients with uncontrolled infection.\n* Patients with bone marrow failure syndrome.\n* Participants who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.\n* Inflammatory bowel disease\n* Moderate to severe pulmonary conditions defined by need for medical intervention and\u002For limiting activities of daily living or shortness of breath with limited exertion.\n* Personal history of pneumonitis.\n* Cardiac conditions.\n* Patients with a history of severe or life-threatening adverse dermatologic reactions such as SJS or toxic epidermal necrolysis, or other severe reactions that have been associated with prior immune checkpoint inhibitor therapy.\n* Active tuberculosis\n* Active autoimmune disease requiring systemic treatment in the past 2 years\n* Chronic HBV infections with active disease\n* Personal known history of HPC who have not completed curative antiviral treatment\n* Personal known history of HIV\n* Receipt of any organ transplantation\n* Treated with other malignancy within 1 year prior to enrollment with the exception of the following: curatively treated basal cell carcinoma, squamous cell carcinoma of the skin, and in situ cervical cancer.\n* Receipt of a live or live-attenuated vaccine within 4 weeks prior to enrollment\n* Previous treatment with relatlimab\n* Patients with ongoing or clinically significant illness, medical or psychiatric conditions that, in the investigator's opinion, could affect the safety of the participant, or could impair assessment of the study's results are not eligible.","ALL","12 Years","39 Years",{"count":20,"type":21},12,"ESTIMATED","INTERVENTIONAL",[24],"PHASE2","The goal of this study is to further evaluate feasibility and tolerability of Opdualag for patients with replication repair deficient HGG, including DIPG.",[27,28,29,30,31],"High Grade Glioma","Diffuse Intrinsic Pontine Glioma","WHO Grade 3 Glioma","WHO Grade 4 Glioma","Replication Repair Deficient","NOT_YET_RECRUITING","2026-06-08",{"date":35,"type":36},"2026-06-12","ACTUAL",{"date":38,"type":21},"2027-03-01",{"date":40,"type":21},"2038-03-01",{"name":42,"class":43},"Nationwide Children's Hospital","OTHER",{"id":45,"slug":46,"hasResults":11,"nctId":47,"briefTitle":48,"officialTitle":49,"acronym":4,"eligibilityCriteria":50,"healthyVolunteers":11,"sex":16,"minAge":51,"maxAge":52,"enrollmentInfo":53,"targetDuration":4,"studyType":22,"phases":55,"briefSummary":57,"conditions":58,"keywords":4,"overallStatus":59,"whyStopped":4,"lastUpdateSubmitDate":60,"lastUpdatePostDateStruct":61,"startDateStruct":63,"completionDateStruct":65,"leadSponsor":67,"locationsCount":69},"100556022","a-pilot-study-investigating-upfront-adaptive-immunotherapy-approach-in-children-adolescent-and-young-adult-caya-patients-with-replication-repair-deficient-rrd-high-grade-gliomas-hgg-100556022","NCT06519682","A Pilot Study Investigating Upfront Adaptive Immunotherapy Approach in Children, Adolescent and Young Adult (CAYA) Patients With Replication-Repair Deficient (RRD) High-Grade Gliomas (HGG)","U-R-Immune Glioma (CA209-1245): A Pilot Study Investigating Upfront Adaptive Immunotherapy Approach in Children, Adolescent and Young Adult (CAYA) Patients With Replication-Repair Deficient (RRD) High-Grade Gliomas (HGG)","Inclusion Criteria:\n\n* 3.1.1 Age: Patients must be ≥12 months and ≤25 years of age at the time of signing informed consent\u002Fassent.\n\n3.1.2 Diagnosis: Patients must have a histologically confirmed diagnosis of glioblastoma.\n\n3.1.3 Proof of RRD: By tumor immunohistochemistry showing functional loss of mismatch repair gene expression (MLH1, MSH2, MSH6, PMS2), or based on prior germline testing confirming congenital mismatch repair deficiency (CMMRD) or Lynch syndrome. To be done locally. Results have to be available within four weeks of last surgery.\n\n3.1.4 Tumor Tissue Specimen: Provide a tumor tissue specimen for molecular profiling, including TMB analysis. Any tumor sequencing data if available at time of enrolment will be recorded for relevant pathogenic variants in the mismatch repair and polymerase-proofreading genes to suggest RRD. A specimen from the time of relapse\u002F progression while on the study is required as well, when applicable.\n\n3.1.5 Favorable immune markers: High PD1 and CD8 positivity as detailed in the lab manual. To be done locally. Results have to be available within 4 weeks of last surgery.\n\n3.1.6 Surgical and disease status: Patients should have had Gross total resection (GTR)\u002FNear Total Resection (NTR) as confirmed by the post-surgery scan. Patients are allowed a second look surgery to achieve NTR\u002FGTR provided no tumor directed systemic or radiation therapy has been administered before this second surgery. Patients should be able to start therapy within 4 weeks of last surgery.\n\n3.1.7 Allowable Prior Therapy: 3.1.7.1 Patients must have recovered from the acute toxic effects of all prior anti-cancer therapies (with the exception of alopecia and lymphopenia). Previous treatment with nivolumab and\u002For other anti- PD-1\u002FPD-L1 inhibitors for other prior tumors (other than high-grade glioma) will be permitted.\n\n3.1.7.2\n\nPrior Therapy: No prior therapy except surgery will be permitted for high grade glioma. If the patient was previously diagnosed and treated for another tumor (other than high grade glioma), the patients must have completed that treatment and have no active disease in order to be enrolled in this trial The following time periods apply for prior therapy for other tumors:\n\n* Cytotoxic chemotherapy: At least 21 days prior to initiation of protocol therapy from the last dose of cytotoxic or myelosuppressive chemotherapy; at least 42 days if prior nitrosourea (such as lomustine, CCNU).\n* Hematopoietic growth factors: At least 7 days prior to initiation of protocol therapy from the last dose of short-acting growth factor; at least 14 days for long-acting.\n* Anti-cancer agents not known to be myelosuppressive: At least 7 days prior to initiation of protocol therapy from the last dose.\n* Interleukins, interferons, and cytokines (other than hematopoietic growth factors): At least 21 days prior to initiation of protocol therapy from the last dose.\n* Antibodies: At least 21 days prior to initiation of protocol therapy from the last dose and toxicity related to prior antibody therapy must be recovered to Grade ≤1.\n* Radiotherapy: At least 14 days prior to initiation of protocol therapy from local radiotherapy; at least 150 days from total body irradiation (TBI), craniospinal radiotherapy, or radiation to\n\n  ≥50% of the pelvis; at least 42 days from other substantial bone marrow radiation.\n* Radiopharmaceutical therapy (e.g., 131I-MIBG): At least 42 days prior to initiation of protocol therapy from systemically administered radiopharmaceutical therapy.\n* Autologous stem cell infusion including boost infusion: At least 42 days prior to initiation of protocol therapy.\n* Cellular therapy: At least 42 days prior to initiation of protocol therapy from any type of cellular therapy.\n\n3.1.8 Performance Status: Lansky play score ≥50 if ≤16 years of age; Karnofsky performance scale ≥50 if \\>16 years of age. See Appendix A. Patients unable to walk due to paralysis but who are using a wheelchair will be considered ambulatory for the purpose of assessing the performance score.\n\n3.1.9 Organ Function: 3.1.9.1\n\nAdequate bone marrow function defined as:\n\n* peripheral absolute neutrophil count (ANC) ≥750\u002Fmm3 (0.75x109\u002FL)\n* platelet count ≥75,000\u002Fmm3 (75x109\u002FL), transfusion independent, defined as not receiving platelet transfusions at least 7 days prior to initiation of protocol therapy 3.1.9.2\n\nAdequate renal function defined as:\n\n-creatinine clearance or radioisotope GFR ≥60 mL\u002Fmin\u002F1.73 m2; OR serum creatinine based on age\u002Fgender 3.1.9.3\n\nAdequate liver function defined as:\n\n* bilirubin (sum of conjugated and unconjugated) ≤1.5 x upper limit of normal (ULN) for age\n* ALT (SGPT) ≤135 U\u002FL (i.e., 3 x ULN). For the purposes of this study, the ULN for ALT (SGPT) is 45 U\u002FL 3.1.9.4\n\nAdequate pulmonary function defined as:\n\n-no evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and pulse oximetry ≥92% while breathing room air 3.1.9.5\n\nAdequate cardiac function defined as:\n\n* no signs or symptoms of heart failure in a patient who has no history of congestive heart failure, no prior exposure to cardiotoxic drugs, and no radiotherapy to the heart; OR\n* shortening fraction of ≥27% or ejection fraction of ≥50% by echocardiogram 3.1.9.6\n\nAdequate pancreatic function defined as:\n\n-serum lipase ≤ ULN at screening 3.1.9.7\n\nViral Infection:\n\n* Human immunodeficiency virus (HIV): Infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to initiation of protocol therapy are eligible.\n* Hepatitis B virus (HBV): Patients with evidence of chronic infection with undetectable viral load are eligible. Suppressive therapy, if indicated, is allowed.\n* Hepatitis C virus (HCV): Infected patients currently on treatment with undetectable viral load are eligible. Patients with a history of infection must have been treated and cured.\n\nNote: Routine screening for HBV, HCV or HIV status prior to enrollment is not required.\n\n3.1.9.8 Informed Consent: All patients and\u002For their parents or legally authorized representatives must have the ability to understand and the willingness to sign, provide a thumbprint (e.g.., for illiterate patients), or use an authorized method to duly document the informed consent in line with the local IRB\u002FIEC requirements and the regulations in force). Assent, where appropriate, will be obtained according to local regulations.\n\nExclusion Criteria:\n\n* 3.2.1\n\nConcomitant Medications:\n\n* Corticosteroids: Patients requiring systemic corticosteroids or other forms of immunosuppressive therapy within 7 days prior to initiation of protocol therapy are not eligible.\n* Following initiation of protocol therapy, systemic corticosteroids or other forms of immunosuppressive therapy are permitted if administered for the treatment of toxicity, tumor flare, or pseudo-progression and can be tapered. In most cases protocol therapy must be held until the dose is tapered to 10 mg\u002Fday prednisone or equivalent. The Protocol Principal Investigator must be consulted prior to resuming treatment.\n* Physiologic corticosteroids up to 5 mg\u002Fday prednisone or equivalent are permitted.\n* Topical, ocular, intra-articular, intra-nasal, and inhaled corticosteroids are permitted.\n* Patients with CNS tumors receiving steroids must be able to discontinue these at least 7 days prior to initiation of protocol therapy.\n* Anti-cancer agents: Patients who are currently receiving other anti-cancer agents are not eligible.\n* Other investigational agents: Patients who are currently receiving or have received any other investigational agent within 14 days prior to initiation of protocol therapy are not eligible.\n\n3.2.2\n\nCNS Tumor Bulk: Patients with CNS tumors with any of the following characteristics on imaging are not eligible:\n\n* Tumor with any evidence of uncal herniation or mass effect leading to severe midline shift\n* Tumor that in the opinion of the local investigator, shows significant mass effect after initial surgery or after second-look surgery.\n\n3.2.3 Uncontrolled Intercurrent Illness: Patients with uncontrolled intercurrent illness including, but not limited to, ongoing active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements are not eligible.\n\n3.2.4 Pregnant and\u002For Breastfeeding: The study agents have the potential for teratogenic or abortifacient effects. Females of reproductive potential must have a negative serum pregnancy test within 72 hours prior to initiation of protocol therapy. Additional pregnancy tests (serum or urine) should be obtained during study participation in accordance with local standards and guidelines.\n\nMales or females of reproductive potential may not participate unless they have agreed to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of treatment, and as follows:\n\n●Females receiving nivolumab must continue an effective method of contraception for a period of 5 months after the last dose of nivolumab.\n\nShould a female patient become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform the investigator immediately.\n\nDue to the unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with the study agents, breastfeeding must be discontinued if the mother is treated on study.\n\nNote: Females of reproductive potential are defined as those who are past the onset of menarche and are not surgically sterile (i.e., bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy).\n\n3.2.5 Autoimmune Disease: Patients with a history of autoimmune disease (such as autoimmune thyroid disease or inflammatory bowel disease) that has required systemic treatment within 2 years prior to initiation of protocol therapy are not eligible.\n\n* Asymptomatic laboratory abnormalities (e.g., ANA, rheumatoid factor, altered thyroid studies) will not render a patient ineligible in the absence of a diagnosis of an autoimmune disorder.\n* Patients with atopy-related conditions such as asthma, allergic rhinitis, or atopic dermatitis are not excluded.\n* Replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroid replacement therapy) is not considered a form of systemic treatment.\n\n3.2.6 Interstitial Lung Disease: Patients with history of interstitial lung disease or pneumonitis are not eligible.\n\n3.2.7 Transplant: Patients who have received previous solid organ transplant or allogenic stem cell transplant are not eligible.\n\n3.2.8 Adverse Reaction to Study Agent(s): Patients with previous Grade 4 life-threatening reaction or other adverse reaction that in the opinion of the investigator would preclude retreatment with nivolumab, and\u002For other PD-1\u002FPD-L1 antibodies are not eligible.\n\n3.2.9 Compliance: Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.\n\n3.2.10 Treatment Start: Patients unable to start study protocol treatment within 14 days from the enrollment date or within 4 weeks of surgery (whichever is earlier).\n\n3.3 Specific Criteria for Domain 2 3.3.1 Proceeding from Domain 1 to Domain 2 For patients already enrolled on the study, the following exclusion criteria specifically apply prior to proceeding to Domain 2.\n\n3.3.1.1 Specific Exclusion Criteria\n\n* Surgery: Patient who cannot have surgery\u002Fbiopsy at recurrence\u002Fprogression on Domain 1 will be discontinued from the study.\n* CNS Tumor Bulk: Patients with CNS tumors with any of the following characteristics on imaging post-surgery\u002Fbiopsy at progression\u002Frecurrence on Domain 1 are not eligible:\n\n  * Tumor \\>= 5cm in the longest dimesion.\n  * Tumor with any evidence of uncal herniation or mass effect leading to severe midline shift\n  * Tumor that in the opinion of the local investigator, shows significant mass effect","12 Months","25 Years",{"count":54,"type":21},20,[56],"NA","This is open label, multicentre, single arm, pilot study of upfront nivolumab in patients with RRD-glioblastoma with favorable immune\u002Fgenomic biomarkers. The purpose of the study is to use upfront immune checkpoint inhibitor (ICI) to delay\u002Favoid radiation for patients with RRD-glioblastoma with favorable clinical (Gross total resection (GTR) or near total resection (NTR)) and biological (RRD, hypermutation, immune activation) biomarkers. At progression, patients will be undergoing surgery\u002Fbiopsy and will get a combination of radiation + ICI followed by maintenance ICI. This model will allow us to additionally study the evolution tumor in response to ICI. The study will have two domains.",[27,31],"RECRUITING","2025-08-22",{"date":62,"type":36},"2025-08-29",{"date":64,"type":36},"2024-12-06",{"date":66,"type":21},"2029-08",{"name":68,"class":43},"Daniel Morgenstern",1]