[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"haematologic-disease\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:haematologic-disease":28},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,4,0,[8,48,81,111],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":20,"targetDuration":4,"studyType":23,"phases":24,"briefSummary":26,"conditions":27,"keywords":29,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":36,"lastUpdatePostDateStruct":37,"startDateStruct":40,"completionDateStruct":42,"leadSponsor":44,"locationsCount":47},"100376326","phase-1-phase-i-study-of-ctl-anti-dp-infusion-post-hematopoietic-stem-cell-transplantation-100376326",false,"NCT04180059","Phase I Study of CTL Anti-DP Infusion Post-hematopoietic Stem Cell Transplantation","A Phase 1 Dose-escalation Study Testing the Feasibility and the Tolerance of Infusion of a Specific Third Party Suicide Gene-transduced Anti-HLA-DPB1*0401 CD4+ T Cell Clone in HLA-DPB1*04:01 Positive Tumor Recipients Receiving an Allotransplant From a HLA-DPB1*04:01 Negative Donor.","CTL-DP 01","Inclusion Criteria:\n\n* Patients HLA-DPB1\\*04:01 positive, with confirmed diagnosis of hematologic malignancies (AML, Myelodysplasic and myeloproliferative syndrome, ALL, non-Hodgkin's lymphoma, Hodgkin's disease, CLL), undergoing an allo-HSCT using a HLA-DPB1\\*04:01 negative donor.\n* The graft can be PBSC (peripheric blood stem cells) or bone marrow.\n* Patients aged between 18-75 years.\n* Patients in complete remission or \\>50% of response (for lymphoma) at time of transplant.\n* have a donor with no contra-indications for mobilization of peripheral blood stem cells using G-CSF (colony-stimulating factors)\n* Affiliation number to the National Health Care System\n* Lack of reactivity of the clone against the donor's cells (PHA-blasts prepared for from PBMCs).\n* For cord blood transplants: cord blood must be HLA-DPB1\\*04:01 negative and the HLA compatibility (A, B, DR) between the cord blood and the recipient must be 4\u002F6, 5\u002F6 or 6\u002F6.\n* ECOG \\\u003C=2 or Karnofsky \\>60%\n* neutrophils ≥ 1 000 cells \u002Fμl and\u002For platelets ≥ 50 000 cells\u002Fμl (growth factor allowed)\n\nExclusion Criteria:\n\n* pregnant or breastfeeding woman\n* patient refusing contraception measure\n* minor\n* Adult patients under guardianship, curatorship or justice protection\n* Patients with post-transplant relapse within the clone injection time (before D100)\n* Karnofsky performance score below 60%or ECOG \\>2\n* Acute and chronic heart failure (NYHA Class III or IV) or symptomatic ischemic heart disease.\n* Severe liver failure (bilirubin \\>30 µmoles\u002FL, SGPT (Serum Glutamo-Oxalacetic Transaminase)\\> 4 X upper limit of normal).\n* Impaired renal function (creatinine clearance \\\u003C 30 ml\u002Fmin)\n* Acute GVHD \\> grade 1\n* Active uncontrolled infection.\n* Denied to provide informed consent\n* Severe neurological or psychiatric disorders as determined by the study physician.\n* Treatment with other investigational drugs following allogeneic transplantation.","ALL","18 Years","75 Years",{"count":21,"type":22},6,"ESTIMATED","INTERVENTIONAL",[25],"PHASE1","For several decades, allogeneic hematopoietic stem cell trans-plantation (allo-HSCT) has remained an important strategy in the management of patients with high-risk hematological malignancies. The acceptance of umbilical cord blood (UCBT) and haploidentical grafts (Haplo) as viable alternative donors for allo-HSCT has increased the options for patients with no matched donors and now ensures that a donor can be identified for virtually all patients. Relapsed disease is a principal threat to these patients and affects 30-50% of them. The therapeutic options for these relapsing patients are diverse but remain largely ineffective in altering their long-term outcomes. Therefore, pre-emptive treatment post allo-HSCT is considered.\n\nMHC (major histocompatibility complex) class II molecules are a family of molecules normally found only on hematopoietic cells. cell-surface proteins are responsible for the regulation of the immune system in humans and are important in disease defense.\n\nThey are the major cause of organ transplant rejections. Different HLA-DPB1 alleles exist in the general population. HLA-DPB1\\*04:01 is the most frequent (70.5%) while HLA-DPB1\\*02:01 represents 32% and HLA-DPB1\\*03:01 20%. In allo-HSCT, the donor and the recipient may express different HLA-DPB1 molecules. HLA-DPB1 matching status has an impact on GVL (graft versus leukemia) and GVHD. In recipients of HSCT, a match for DPB1 is associated with a significantly increased risk of disease relapse, irrespective of the matching status of other HLA molecules.. Therefore, one could anticipate that a mismatched of HLA class II could induce a selective GVL reactivity without GVHD.\n\nHLA-DP-expressing B cell and myeloid malignancies can be recognized and lysed by HLA-DP-specific T cells. The majority of leukemic cells (Acute Myeloid Leukemia, Acute Lymphoid Leukemia, Chronic Lymphoid Leukemia) express HLA-DP. A T cell clone recognizing specifically HLA-DPB1\\*0401 has been developed as a permanent cell line This clone has been demonstrated to be able to kill HLA-DPB1\\*0401 positive leukemic cells. In addition, this clone harbors a special suicide gene allowing the destruction of the clone in presence of a specific anti-viral drug named ganciclovir.\n\nWe hypothesize that infusion of a third party suicide gene-transduced T cell clone directed against HLA-DPB1\\*401 might protect against possible relapse of hematological malignancies.\n\nWe propose to inject iv escalating dose of a third party clone recognizing HLA-DPB1\\*04:01, 4 to 5 months following transplantation (when immunosuppressive drugs have been discontinued) in patients HLA-DPB1\\*04:01 positive with a donor HLA-DPB1\\*04:01 negative to evaluate the feasibility, toxicity, benefits of this immune intervention.",[28],"Haematologic Disease",[30,31,32,33,34],"hematopoietic stem cell transplantation","lymphocyte infusion","cytotoxic T lymphocyte","HLA-DP","T cell therapy","RECRUITING","2026-01-23",{"date":38,"type":39},"2026-01-26","ACTUAL",{"date":41,"type":39},"2020-02-09",{"date":43,"type":22},"2027-08",{"name":45,"class":46},"Nantes University Hospital","OTHER",1,{"id":49,"slug":50,"hasResults":11,"nctId":51,"briefTitle":52,"officialTitle":53,"acronym":54,"eligibilityCriteria":55,"healthyVolunteers":56,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":57,"targetDuration":4,"studyType":59,"phases":4,"briefSummary":60,"conditions":61,"keywords":4,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":71,"lastUpdatePostDateStruct":72,"startDateStruct":74,"completionDateStruct":76,"leadSponsor":78,"locationsCount":80},"100533565","a-clinical-study-to-map-the-hla-genomic-region-in-the-greek-population-100533565","NCT06227468","A Clinical Study to Map the HLA Genomic Region in the Greek Population","A Clinical Study to Map the HLA GENomic Region and Its potEntial aSsocIation With Selected diSeases in the Greek Population","GENESIS","Inclusion Criteria:\n\nThe study will include adult subjects (age ≥ 18) that:\n\n* possess a Greek social security number and are visiting hospitals\u002Fclinics, and\u002For other private laboratory institutions (incl. clinics and health care groups) as part of standard clinical practice in Greece,\n* are willing and able to provide written informed consent to participate in the study according to the study protocol.\n\nExclusion Criteria:\n\n* Subjects not able to provide written informed consent (e.g. ICU patients, mental illness patients, lack of legal capacity).\n* Subjects who have had an allogeneic (non-self-donor):\n\n  * bone marrow transplant\n  * stem cell transplant\n  * blood transfusion less than two weeks prior to buccal swab sample collection\n  * liver transplant\n* Subjects who participated in an interventional clinical trial in the past that according to the subject's physician opinion might have had an impact on their HLA genome.",true,{"count":58,"type":22},12000,"OBSERVATIONAL","The aim of GENESIS clinical study is to map the HLA genomic region in the Greek population and evaluate possible correlations with selected underlying diseases.",[62,63,64,65,66,67,68,69,28,70],"Healthy","Respiratory Disease","Chronic Renal Failure","Cardiovascular Diseases","Metabolic Disease","Psychiatric Disorder","Neurologic Disorder","Gastrointestinal Diseases","Rheumatologic Disease","2024-01-25",{"date":73,"type":39},"2024-01-26",{"date":75,"type":39},"2023-12-12",{"date":77,"type":22},"2026-08-31",{"name":79,"class":46},"Athens LifeTech Park",8,{"id":82,"slug":83,"hasResults":11,"nctId":84,"briefTitle":85,"officialTitle":86,"acronym":4,"eligibilityCriteria":87,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":88,"targetDuration":4,"studyType":23,"phases":90,"briefSummary":92,"conditions":93,"keywords":4,"overallStatus":35,"whyStopped":4,"lastUpdateSubmitDate":101,"lastUpdatePostDateStruct":102,"startDateStruct":104,"completionDateStruct":106,"leadSponsor":108,"locationsCount":110},"100483343","phase-1-a-study-to-investigate-safety-and-clinical-activity-of-belantamab-mafodotin-in-combination-with-lenalidomide-dexamethasone-and-nirogacestat-in-patients-with-transplant-ineligible-newly-diagnosed-multiple-myeloma-100483343","NCT05573802","A Study to Investigate Safety and Clinical Activity of Belantamab Mafodotin in Combination With Lenalidomide, Dexamethasone and Nirogacestat in Patients With Transplant Ineligible Newly Diagnosed Multiple Myeloma","A Phase 1\u002F2, Dose and Schedule Evaluation Study to Investigate the Safety and Clinical Activity of Belantamab Mafodotin Administrated in Combination With Lenalidomide, Dexamethasone and Nirogacestat in Patients With Transplant Ineligible Newly Diagnosed Multiple Myeloma","Inclusion Criteria:\n\n1. Participant must be \\>18 years of age\n2. Monoclonal plasma cells in the bone marrow (BM) ≥10% or presence of a biopsy proven plasmacytoma and documented Multiple Myeloma (MM) satisfying at least one of the calcium, renal, anemia, bone (CRAB) criteria or biomarkers of malignancy criteria:\n\n   CRAB criteria:\n\n   i. Hypercalcemia: serum calcium \\>0.25 mmol\u002FL (\\>1 mg\u002FdL) higher than upper limit of normal (ULN) or \\>2.75 mmol\u002FL (\\>11 mg\u002FdL).\n\n   ii. Renal insufficiency: creatinine clearance (CrCI) \\\u003C40mL\u002Fmin or serum creatinine \\>177 μmol\u002FL (\\>2 mg\u002FdL).\n\n   iii. Anemia: hemoglobin \\>2 g\u002FdL below the lower limit of normal or hemoglobin \\\u003C10 g\u002FdL.\n\n   iv. Bone lesions: one or more osteolytic lesions on skeletal radiography, Computed tomography (CT), or Positron emission tomography (PET-CT).\n\n   Biomarkers of Malignancy:\n   1. Clonal BM plasma cell percentage ≥60%.\n   2. Involved: uninvolved serum free light chain (sFLC) ratio ≥100.\n   3. More than 1 focal lesion on magnetic resonance imaging (MRI) studies.\n3. Must have at least ONE aspect of measurable disease, defined as one of the following:\n\n   * Urine M-protein excretion ≥200 mg\u002F24 hrs (≥0.2 g\u002F24 hrs), or\n   * Serum M-protein concentration ≥0.5 g\u002FdL (≥5.0 g\u002FL), or\n   * Serum FLC assay: involved FLC level ≥10 mg\u002FdL (≥100 mg\u002FL) and an abnormal serum FLC ratio (\\\u003C0.26 or \\>1.65).\n4. Not a candidate for high-dose chemotherapy with autologous stem cell transplantation due to presence of significant comorbid condition(s), such as cardiac, pulmonary or other major organ dysfunction that are likely to have a negative impact on tolerability of high dose chemotherapy with stem cell transplantation. The patients will be assessed with the IMWG frailty index, a scoring system based on age, comorbidities, and cognitive and physical conditions, which is recommended by the European Society for Medical Oncology (ESMO) guidelines. Patients with International Myeloma Working Group (IMWG) frailty index score 1 or 2 will be considered transplant ineligible. The reason(s) for transplant ineligibility will be collected in the case report forms (CRFs).\n5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2.\n6. Adequate organ system function as defined by the below laboratory assessments. Hematologic\n\n   * Absolute neutrophil count (ANC) ≥1.25 X 10\\^9\u002FL; granulocyte colony-stimulating factor (G-CSF) use for the past 14 days is NOT allowed.\n   * Hemoglobin ≥8.0 g\u002FdL; transfusions are not permitted in the past 14 days prior to the assessment. Erythropoietin use is allowed.\n   * Platelet count ≥50 x 10\\^9\u002FL if the BM is \\>50% involved in myeloma. Otherwise, ≥75 x 10\\^9\u002FL; transfusions or platelet stimulating agents are NOT allowed in the past 14 days prior to the assessment.\n\n   Hepatic\n   * Total bilirubin ≤1.5xULN (isolated bilirubin ≥1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \\\u003C35%).\n   * ALT ≤ 2.5xULN. Renal\n   * Estimate glomerular filtration rate (eGFR) ≥30 mL\u002Fmin\u002F1.73 m2; calculated using the Modified Diet in Renal Disease (MDRD) formula.\n   * Spot urine (albumin\u002Fcreatinine ratio) \\\u003C500 mg\u002Fg (56 mg\u002Fmmol) OR\n   * Urine Dipstick: Negative trace; if ≥1+ only eligible if confirmed \\\u003C500 mg\u002Fg \\[56 mg\u002Fmmol\\] by albumin\u002Fcreatinine ratio (spot urine from first void).\n7. Female participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies:\n\n   A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:\n   * Is not a woman of childbearing potential (WOCBP) defined as follows:\n   * ≥ 45 years of age and has not had menses for \\> 1 year\n   * Patients who have been amenorrhoeic for \\\u003C 2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation\n   * Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure.\n\n   OR\n   * Is a WOCBP and using two methods of reliable birth control (one method that is highly effective and one additional effective \\[barrier\\] method), beginning 4 weeks before initiating treatment with lenalidomide, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of lenalidomide treatment. WOCBP participants must use one method of reliable birth control that is highly effective for 4 months following discontinuation of belantamab mafodotin. WOCBP must also agree not to donate eggs (ova, oocytes) for the purpose of reproduction during treatment, during dose interruptions and for 28-days following the last dose of lenalidomide or 4 months following discontinuation of belantamab mafodotin treatment, whichever is longer.\n\n   A WOCBP must have two negative pregnancy tests before therapy initiation. The first test should be performed within 10-14 days, and the second test within 24 hours before the start of lenalidomide therapy.\n\n   The participant should not receive lenalidomide until the investigator has verified that the results of these pregnancy tests are negative. The investigator should evaluate the effectiveness of the contraceptive method in relation to the first dose of the study treatment. The investigator is responsible for a review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with a nearly undetected pregnancy.\n\n   WOCBP is a female who:\n   * has achieved menarche at some time point\n   * has not undergone a hysterectomy or bilateral oophorectomy or\n   * has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).\n8. Male participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies:\n\n   Male participants are eligible to participate if they agree to the following during the intervention period and until 28 days after the last dose of lenalidomide or 6 months after the last dose of belantamab mafodotin, whichever is longer, to allow for clearance of any altered sperm.\n   * Refrain from donating sperm\n\n   PLUS either:\n   * Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent, OR\n   * Must agree to use contraception\u002Fbarrier as detailed below:\n\n   Agree to use a male condom, even if they have undergone a successful vasectomy, and female partner to use an additional highly effective contraceptive method with a failure rate of \\\u003C1% per year as when having sexual intercourse with a woman of childbearing potential (including pregnant females).\n9. Participants must be able to understand the study procedures and agree to participate in the study by providing written informed consent.\n\nExclusion Criteria:\n\n1. Prior systemic therapy for MM or Smoldering MM.\n\n   * NOTE 1: An emergency course of steroids (defined as not greater than 40 mg of dexamethasone \\[or equivalent\\] per day for a maximum of 4 days \\[i.e., a total of 160 mg\\]) is permitted.\n   * NOTE 2: Focal palliative radiation is permitted before enrollment, provided that: it occurred at least 2 weeks before the first dose of the study drug; the participant has recovered from radiation-related toxicities; and the participant did not require corticosteroid administration (for a longer period than that specified in NOTE 1 above) for radiation-induced AEs.\n2. Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National Cancer Institute Common Toxicity Criteria for AEs version 5.\n3. Major surgery within 2 weeks before the first dose of the study drug.\n\n   * NOTE 1: patients who underwent major surgery must be clinically stable to be enrolled in the study.\n   * NOTE 2: major surgery shall be defined based on the Investigator's judgment according to the extent and complexity of the procedure, its pathophysiological consequences and consecutive clinical outcomes.\n4. Presence of active renal condition (infection, requirement for dialysis or any other significant condition that could affect the participant's safety). Participants with isolated proteinuria resulting from MM are eligible, provided that they fulfil the other inclusion criteria.\n5. Any serious and\u002For unstable pre-existing medical, psychiatric disorder, or other conditions (including laboratory abnormalities) that could interfere with the participant's safety, obtaining informed consent, or compliance with the study procedures.\n6. Evidence of active mucosal or internal bleeding uncontrolled by local therapy and not explained by reversible coagulopathy.\n7. Current active liver or biliary disease (except for Gilbert's syndrome or asymptomatic gallstones, or otherwise stable chronic liver disease as per the investigator's assessment).\n8. Participants with previous or concurrent malignancies other than MM are excluded. Exceptions are surgically treated cervical carcinoma in situ or any other malignancy that has been considered medically stable for at least 2 years. The participant must not be receiving active therapy other than hormonal therapy for this disease.\n\n   * NOTE: Participants with curatively treated non-melanoma skin cancer are allowed without a 2-year restriction.\n9. Evidence of cardiovascular risk including any of the following:\n\n   * Evidence of current clinically significant untreated arrhythmias, including clinically significant electrocardiogram (ECG) abnormalities, second degree (Mobitz Type II), or third degree atrioventricular (AV) block.\n   * History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of screening.\n10. Class III or IV heart failure as defined by the New York Heart Association functional classification system.\n11. Uncontrolled hypertension.\n12. Active infection requiring treatment.\n13. Known HIV infection, unless the participant can meet all of the following criteria:\n\n    * Established anti-retroviral therapy (ART) for at least 4 weeks and HIV viral load \\\u003C400 copies\u002FmL.\n    * CD4+ T-cell (CD4+) count ≥350 cells\u002FuL.\n    * No history of AIDS-defining opportunistic infections within the last 12 months.\n\n      * NOTE: consideration must be given to ART and prophylactic antimicrobials that may have a drug:drug interaction and\u002For overlapping toxicities with belantamab mafodotin or other combination products as relevant\n14. Seropositivity for hepatitis B (defined by a positive test for hepatitis B surface antigen \\[HBsAg\\]).\n\n    * NOTE 1: Participants with resolved infection (i.e., participants who are positive for antibodies to hepatitis B core antigen \\[antiHBc\\] or antibodies to hepatitis B surface antigen \\[antiHBs\\]) must be screened using real-time polymerase chain reaction (PCR). Those who are PCR positive will be excluded.\n    * NOTE 2: presence of antiHBs indicating previous vaccination will not constitute an exclusion criterion.\n15. Positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months before the first dose of the study treatment unless the participant can meet the following criteria:\n\n    * RNA test negative\n    * Successful anti-viral treatment (usually 8 weeks duration) is required, followed by a negative hepatitis C virus RNA test after a washout period of at least 4 weeks.\n16. Current corneal epithelial disease except for mild punctate keratopathy.\n\n    * NOTE: Participants with mild punctate keratopathy are allowed. Mild (Grade 1) punctuate keratopathy is characterized by the appearance of only a few, if any, microcyst-like epithelial changes (MECs), as identified in the slit-lamp examination, with a low density (non-confluent), and predominantly (≥80%) located in the periphery of the cornea\n17. Intolerance or contraindications to anti-viral prophylaxis.\n18. Unable to tolerate antithrombotic prophylaxis.\n19. AL amyloidosis (light chain amyloidosis), active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes) or active plasma cell leukemia at the time of screening.\n20. Exhibiting clinical signs of or with known history of meningeal or central nervous system involvement by MM.\n21. Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin or any of the components of the study treatment.\n22. Use of an investigational drug within 14 days or 5 half-lives (whichever is shorter) preceding the first dose of study drug.\n23. Plasmapheresis within 7 days before the first dose of the study drug.\n24. Participants with active small and\u002For large intestinal disease which is not adequately controlled with the appropriate treatment (e.g., uncontrolled diarrheal disease).\n25. Participants with uncontrolled skin disease.\n26. Participants with any condition causing hypophosphatemia, hypokalemia or hypomagnesemia which is refractory to electrolyte replacement.\n27. Participants with previous administration of a gamma secretase inhibitor.\n28. Participants with concomitant administration of a strong or moderate CYP3A4 inhibitor or inducer.\n29. Any serious and\u002For unstable pre-existing medical, psychiatric disorder or other conditions (including lab abnormalities) that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures.\n30. Participant must not have received a live or live-attenuated vaccine within 30 days prior to first dose of belantamab mafodotin.\n31. Participant should not use contact lenses while receiving belantamab mafodotin.\n32. Because of the embryo-fetal risk of lenalidomide, all participants must adhere to the lenalidomide pregnancy prevention program applied in their region.",{"count":89,"type":22},36,[25,91],"PHASE2","This is a phase 1\u002F2, open-label study designed to assess the safety and clinical activity of different belantamab mafodotin doses in combination with lenalidomide, dexamethasone and nirogacestat in patients with transplant ineligible newly diagnosed multiple myeloma.\n\nThis will be a 2-part study. In part 1 participants will be enrolled in one cohort to receive belantamab mafodotin in combination with lenalidomide, dexamethasone and nirogacestat and will determine the recommended phase 2 dose (RP2D) to be further evaluated for safety and clinical activity in the dose expansion cohort. The RP2D dose will be used in future studies in the transplant-ineligible newly diagnosed multiple myeloma (NDMM) setting. In the dose expansion phase (Part 2) an expansion cohort will be treated with the RP2D. The expansion cohort will randomize participants (1:1) in two groups to evaluate two alternate dose modification guidelines for corneal AEs. Part 2 of the study will also evaluate an alternative dose modification guideline for corneal adverse events (AEs).\n\nOverall, approximately 36 participants will be enrolled in the study. Participant follow-up will continue up to 3 years after the last participant is enrolled (follow-up period range: 3-4 years). The estimated accrual period will be 12 months, corresponding to an approximate total study duration of 4 years.",[94,95,96,97,98,99,28,100],"Multiple Myeloma","Neoplasms","Neoplasm, Plasma Cell","Gammopathy, Monoclonal","Paraproteinemias","Blood Protein Disorders","Corneal Disease","2023-10-20",{"date":103,"type":39},"2023-10-24",{"date":105,"type":39},"2023-07-14",{"date":107,"type":22},"2026-10-31",{"name":109,"class":46},"Hellenic Society of Hematology",2,{"id":112,"slug":113,"hasResults":11,"nctId":114,"briefTitle":115,"officialTitle":116,"acronym":4,"eligibilityCriteria":117,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":118,"targetDuration":4,"studyType":23,"phases":120,"briefSummary":121,"conditions":122,"keywords":4,"overallStatus":125,"whyStopped":4,"lastUpdateSubmitDate":126,"lastUpdatePostDateStruct":127,"startDateStruct":129,"completionDateStruct":131,"leadSponsor":132,"locationsCount":4},"100483964","phase-1-a-study-to-investigate-the-safety-and-clinical-activity-of-belantamab-mafodotin-in-combination-with-daratumumab-pomalidomide-and-dexamethasone-in-patients-with-relapsed-refractory-multiple-myeloma-previously-treated-with-one-line-therapy-who-are-lenalidomide-refractory-100483964","NCT05581875","A Study to Investigate the Safety and Clinical Activity of Belantamab Mafodotin in Combination With Daratumumab, Pomalidomide and Dexamethasone in Patients With Relapsed\u002F Refractory Multiple Myeloma Previously Treated With One Line Therapy Who Are Lenalidomide Refractory","A Phase 1\u002F2, Dose and Schedule Evaluation Study to Investigate the Safety and Clinical Activity of Belantamab Mafodotin Administered in Combination With Daratumumab, Pomalidomide and Dexamethasone in Patients With Relapsed\u002F Refractory Multiple Myeloma Previously Treated With One Line of Therapy Who Are Lenalidomide Refractory.","Inclusion Criteria:\n\n1. Participant must be ≥18 years or older.\n2. Documented diagnosis of Multiple Myeloma (MM) as per International Myeloma Working Group (IMWG) criteria.\n3. Must have at least ONE aspect of measurable disease, defined as one of the following:\n\n   1. Urine M-protein excretion ≥200 mg\u002F24 hrs (≥0.2 g\u002F24 hrs), or\n   2. Serum M-protein concentration ≥0.5 g\u002FdL (≥5.0 g\u002FL), or\n   3. Serum Free Light Chain (FLC) assay: involved FLC level ≥10 mg\u002FdL (≥100 mg\u002FL) and an abnormal serum FLC ratio (\\\u003C0.26 or \\>1.65).\n4. Eastern Cooperative Oncology Group performance status of 0-2.\n5. Adequate organ system function as defined by the below laboratory assessments. Hematologic\n\n   1. Absolute neutrophil count (ANC) ≥1.5 X 109\u002FL; granulocyte colony stimulating factor use within the past 14 days is NOT permitted.\n   2. Hemoglobin ≥8.0 g\u002FdL; transfusions within the past 14 days are NOT permitted. Erythropoietin use is allowed.\n   3. Platelet count ≥50 x 109\u002FL if Bone Marrow (BM) is \\>50% involved in myeloma. Otherwise ≥75 x 109\u002FL; transfusions within the past 14 days are NOT allowed to reach this level.\n\n   Hepatic\n   1. Total bilirubin ≤1.5xULN (isolated bilirubin ≥1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \\\u003C35%).\n   2. Alanine aminotransferase (ALT) ≤ 2.5xUpper Limit of Normal (ULN). Renal\n\n   \u003C!-- -->\n\n   1. Estimate glomerular filtration rate (eGFR) ≥30 mL\u002Fmin\u002F1.73 m2; calculated using the Modified Diet in Renal Disease (MDRD) formula.\n   2. Spot urine (albumin\u002Fcreatinine ratio) ≤500 mg\u002Fg (56 mg\u002Fmmol) OR\n   3. Urine Dipstick: Negative trace; if ≥1+ only eligible if confirmed ≤500 mg\u002Fg \\[56 mg\u002Fmmol\\] by albumin\u002Fcreatinine ratio (spot urine from first void).\n6. Female participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies:\n\n   A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:\n   * Is not a woman of childbearing potential (WOCBP) defined as follows:\n\n     1. ≥45 years of age and has not had menses for \\> 1 year\n     2. Participants who have been amenorrhoeic for \\\u003C 2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation\n     3. Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure.\n\n        OR\n   * Is a WOCBP and using two methods of reliable birth control (one method that is highly effective and one additional effective \\[barrier\\] method), beginning 4 weeks before initiating treatment with pomalidomide, during therapy, during dose interruptions, and continuing for 4 weeks following discontinuation of pomalidomide treatment. WOCBP participants must use one method of reliable birth control that is highly effective for 4 months following discontinuation of belantamab mafodotin or 3 months following the discontinuation of daratumumab. WOCBP must also agree not to donate eggs (ova, oocytes) for the purpose of reproduction during treatment, during dose interruptions and for 28-days following the last dose of pomalidomide or 3 months following discontinuation of daratumumab treatment or 4 months following discontinuation of belantamab mafodotin treatment whichever is longer.\n\n   A WOCBP must have two negative pregnancy tests before therapy initiation. The first test should be performed within 10-14 days and the second test within 24 hours before the start of pomalidomide therapy.\n\n   The participant should not receive pomalidomide until the Investigator has verified that the results of these pregnancy tests are negative. The Investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study treatment. The Investigator is responsible for a review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with a nearly undetected pregnancy.\n7. Male participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies:\n\n   Male participants are eligible to participate if they agree to the following during the intervention period and until 28 days after the last dose of pomalidomide or 3 months following the discontinuation of daratumumab or 6 months after the last dose of belantamab mafodotin, whichever is longer, to allow for clearance of any altered sperm.\n\n   • Refrain from donating sperm\n\n   PLUS either:\n   * Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent, OR\n   * Must agree to use contraception\u002Fbarrier as detailed below:\n\n   Agree to use a male condom, even if they have undergone a successful vasectomy, and female partner to use an additional highly effective contraceptive method with a failure rate of \\\u003C1% per year as when having sexual intercourse with a woman of childbearing potential (including pregnant females).\n8. Participants must be able to understand the study procedures and agree to participate in the study by providing written informed consent.\n9. Participant must have received only 1 prior line of therapy (including lenalidomide) and be lenalidomide refractory at any lenalidomide dose (i.e., nonresponsive while on lenalidomide therapy, or progresses within 60 days of last therapy with lenalidomide).\n\nExclusion Criteria:\n\n1. Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National Cancer Institute, Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 5.\n2. Major surgery within 4 weeks before the first dose of study drug\n\n   * NOTE 1: participant must be clinically stable following a major surgery to be entered in the study.\n   * NOTE 2: major surgery shall be defined based on the Investigator's judgment according to the extent and complexity of the procedure, its pathophysiological consequences and consecutive clinical outcomes.\n3. Presence of active renal condition (infection, requirement for dialysis, or any other significant condition that could affect participant's safety). Participants with isolated proteinuria resulting from MM are eligible, provided that they fulfil the other inclusion criteria.\n4. Any serious and\u002For unstable pre-existing medical or psychiatric disorder, or other conditions (including laboratory abnormalities) that could interfere with participant's safety, obtaining informed consent, or compliance to the study procedures.\n5. Evidence of active mucosal or internal bleeding uncontrolled by local therapy and not explained by reversible coagulopathy.\n6. Current active unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis (except for Gilbert's syndrome or asymptomatic gallstones; otherwise, stable non-cirrhotic chronic liver disease; or hepatobiliary involvement of malignancy as per the Investigator's assessment).\n7. Participants with previous or concurrent malignancies other than MM are excluded. Exceptions are surgically treated cervical carcinoma in situ, or any other malignancy that has been considered medically stable for at least 2 years. The participant must not be receiving active therapy, other than hormonal therapy for this disease.\n\n   * NOTE: Participants with curatively treated non-melanoma skin cancer are allowed without a 2-year restriction.\n8. Evidence of cardiovascular risk including any of the following:\n\n   * Evidence of current clinically significant untreated arrhythmias, including clinically significant electrocardiogram (ECG) abnormalities, second degree (Mobitz Type II), or third degree atrioventricular block.\n   * Screening 12-lead ECG showing a baseline QT interval \\>470 msec\n   * History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening.\n   * Class III or IV heart failure as defined by the New York Heart Association functional classification system\n   * Uncontrolled hypertension.\n9. Participant has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume in 1 second \\[FEV1\\] \\\u003C50% of predicted normal), persistent asthma, or a history of asthma within the last 2 years (controlled intermittent asthma or controlled mild persistent asthma is allowed).\n\n   NOTE: Participants with known or suspected COPD must have a FEV1 test at screening.\n10. Active infection requiring treatment.\n11. Known human immunodeficiency virus infection, unless the participant can meet all of the following criteria:\n\n    * Established anti-retroviral therapy for at least 4 weeks and HIV viral load \\\u003C400 copies\u002FmL.\n    * CD4+ T-cell (CD4+) count ≥350 cells\u002FuL.\n    * No history of AIDS-defining opportunistic infections within the last 12 months.\n\n      * NOTE: consideration must be given to ART and prophylactic antimicrobials that may have a drug:drug interaction and\u002For overlapping toxicities with belantamab mafodotin or other combination products as relevant\n12. To be seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \\[HBsAg\\]) at screening or within 3 months prior to first dose of study treatment.\n\n    * NOTE 1: Participants with resolved infection (i.e., participants who are positive for antibodies to hepatitis B core antigen \\[antiHBc\\] or antibodies to hepatitis B surface antigen \\[antiHBs\\]) must be screened using real-time polymerase chain reaction (PCR). Those who are PCR positive will be excluded.\n    * NOTE 2: presence of antiHBs indicating previous vaccination will not constitute an exclusion criterion.\n13. Positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months before the first dose of study treatment unless the participant can meet the following criteria:\n\n    * RNA test negative\n    * Successful anti-viral treatment (usually 8 weeks duration) is required, followed by a negative hepatitis C virus (HCV) RNA test after a washout period of at least 4 weeks.\n14. Current corneal epithelial disease except for mild punctate keratopathy.\n\n    * NOTE: Participants with mild punctate keratopathy are allowed.\n15. Intolerance or contraindications to anti-viral prophylaxis.\n16. Unable to tolerate antithrombotic prophylaxis.\n17. Active or history of venous thromboembolism within past 3 months.\n18. AL amyloidosis (light chain amyloidosis), active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes) or active plasma cell leukemia at the time of screening.\n19. Exhibiting clinical signs of or with a known history of meningeal or central nervous system involvement by MM.\n20. Known intolerance or immediate or delayed hypersensitivity reaction or idiosyncratic reaction to: drugs chemically related to belantamab mafodotin, or any of the components of the study treatment; daratumumab subcutaneous (SC) or to any of its excipients; or infused protein products, sucrose, histidine, and polysorbate 80.\n21. Use of an investigational drug within 14 days or 5 half-lives (whichever is longer) preceding the first dose of study drug.\n22. Participant who has received prior treatment with daratumumab, pomalidomide or belantamab mafodotin will be excluded.\n\n    * NOTE: Participants who received induction treatment with daratumumab (max 4 cycles) will be allowed as long as 6 months have passed since their treatment with daratumumab and cycle 1 day 1 (C1D1).\n23. Plasmapheresis within 7 days before the first dose of study drug.\n24. Participants with uncontrolled skin disease.\n25. Participant must not have received a live or live-attenuated vaccine within 30 days prior to first dose of belantamab mafodotin.\n26. Participant should not use contact lenses while receiving belantamab mafodotin.",{"count":119,"type":22},48,[25,91],"This is a phase 1\u002F2, open label, single-center study designed to assess the safety and preliminary clinical activity of different belantamab mafodotin doses in combination with daratumumab, pomalidomide, and dexamethasone (DPd) in patients with Relapsed\u002F Refractory Multiple Myeloma (RRMM) previously treated with one line of therapy who are lenalidomide refractory.\n\nThis will be a 2-Part study. Part 1 will evaluate the safety of belantamab mafodotin in combination with DPd in 2 cohorts and determine the Recommended Phase 2 Dose (RP2D). In the dose expansion phase (Part 2) an expansion cohort will be treated with the RP2D. The expansion cohort will randomize participants (1:1) in two groups to evaluate two alternate dose modification guidelines for corneal AEs. Part 2 will further evaluate the safety and assess the preliminary clinical activity of the belantamab mafodotin RP2D in combination with DPd.\n\nOverall, approximately 48 participants will be enrolled in the study. Participant follow-up will continue up to 3 years after the last participant is randomized. The estimated accrual period will be 12 months corresponding to an approximate total study duration of 4 years.",[94,123,95,97,98,99,28,100,124],"Multiple Myeloma in Relapse","Neoplasms, Plasma Cell","NOT_YET_RECRUITING","2022-10-13",{"date":128,"type":39},"2022-10-17",{"date":130,"type":22},"2022-10-20",{"date":107,"type":22},{"name":109,"class":46}]