2025-522803-60-00招募中2 期
A Phase 2, open-label, randomized, dose optimization study evaluating the efficacy and safety of belantamab mafodotin administered in combination with cyclophosphamide, bortezomib, and dexamethasone in adult participants with newly diagnosed amyloid light chain amyloidosis (ALANIS)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 17
- 试验地点
- 10
- 主要终点
- Overall Complete Hematologic Response (CHR) rate, defined as the proportion of participants who achieve a CHR, according to the consensus guidelines for AL amyloidosis, during or after study treatment initiation.
研究概览
简要总结
To evaluate the efficacy of belantamab mafodotin when administered in combination with cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in participants with Newly diagnosed amyloid light chain (ND AL) amyloidosis.
入排标准
- 年龄范围
- 18 years 至 64 years（18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Is at least 18 years of age or the legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the informed consent form.
- •Has histologically confirmed newly diagnosed primary AL amyloidosis according to the following criteria (a, b, and c must be present for the diagnosis): a. Presence of an amyloid-related systemic syndrome with 1 or more organs involved b. Positive amyloid staining by Congo red stain with apple green birefringence on polarized light microscopy in any tissue, AND at least 1 of the tests listed in the Protocol Section 5.1.2 to confirm amyloid type as AL. c. Evidence of a monoclonal plasma cell proliferative disorder.
- •Measurable clonal disease as defined by at least 1 of the following: ─ Serum monoclonal protein ≥0.5 g/dL ─ Involved serum FLC ≥5.0 mg/dL with an abnormal kappa:lambda ratio or the difference between involved and uninvolved light chain, dFLC ≥5 mg/dL
- •Not considered candidate for high-dose chemotherapy with ASCT as part of first line of therapy
- •Is willing to use adequate contraception. Contraceptive use by male and female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male participants Male participants are eligible to participate if they agree to the following during the Treatment period and for at least 6 months after the last dose of study intervention of belantamab mafodotin, for 4 months from the last dose of cyclophosphamide, and for 5 months from the last dose of bortezomib (whichever is longer) to allow for clearance of any altered sperm: ─ Refrain from donating semen PLUS either: ─ 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 ─ Must agree to use contraception/barrier as detailed in the Protocol Section 5.1.
- •Female participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies: ─ Is a PONCBP [Protocol Appendix 4] OR ─ Is a POCBP and must commit to either abstain continuously from heterosexual sexual intercourse or to use 1 highly effective form of contraception. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy or bilateral oophorectomy. Contraception must begin 4 weeks prior to dosing, continue during therapy, during dose interruptions and continue for 1 year after discontinuation of cyclophosphamide and 8 months from the last dose of bortezomib. Thereafter, POCBP on belantamab mafodotin regimen must use 1 contraceptive method that is highly effective (with a failure rate of <1% per year) preferably with low user dependency during the Treatment period and for 4 months after the last dose of belantamab mafodotin. All POCBP must agree not to donate eggs (ova, oocytes) for the purpose of reproduction during the study, 1 year after stopping cyclophosphamide, 8 months after stopping bortezomib, and for 4 months after the last dose belantamab mafodotin, whichever is longer. A POCBP must have 2 negative highly sensitive serum pregnancy tests before starting treatment, the first may be performed within 14 days from C1D1, the second within 24 hours before the first dose of study intervention. See the Protocol Section 5.1.3 for additional details and requirements.
- •Is capable of giving signed informed consent as described in the Protocol Section 10.1.3, including compliance with the requirements and restrictions listed in the ICF and in the protocol.
- •Has an ECOG performance status of 0, 1 or 2, with no deterioration in the 2 weeks before enrollment (see the Protocol Section 10.8).
- •Has adequate organ function as defined below. Specimens must be collected within 3 days prior to the start of study intervention administration. ─ ANC ≥1.0x109/L ─ Platelets ≥75x109/L ─ Total Bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated, and direct bilirubin is <35%) ─ ALT ≤2.5xULN if no hepatic involvement of AL amyloidosis ≤3xULN if hepatic involvement of AL amyloidosis is present ─ eGFR ≥30 mL/min/1.73 m2 (If measured or calculated GFR (e.g., mGFR, creatinine clearance) is required or used ≥30 mL/min)
排除标准
- •Has a previous or current diagnosis of plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes (POEMS) syndrome or symptomatic multiple myeloma (MM), as per International Myeloma Working Group criteria for MM including the presence of lytic bone disease (≥1 osteolytic lesion on imaging tests skeletal radiography, CT scan, positron emission tomography/CT scan or MRI), plasmacytomas, or clonal bone marrow plasma cells ≥60%.
- •Has known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin, cyclophosphamide, bortezomib, dexamethasone, boron or mannitol or any other components or excipients or other allergy that, in the opinion of the investigator or GSK medical monitor, contraindicates participation in the study.
- •Has any serious and/or unstable medical or psychiatric disorder or other condition(s) (including laboratory assessment abnormalities) that could interfere with the participant’s safety, obtaining of informed consent, or compliance with the study procedures.
- •Has active infection or active bleeding.
- •Has intolerance or contraindications to antiviral prophylaxis.
- •Has known HIV infection, unless the participant can meet all of the following criteria: ─ Established ART for at least 4 weeks and HIV viral load <400 copies/mL within the screening period. ─ CD4+ T-cell (CD4+) counts ≥350 cells/μL. ─ No history of AIDS-defining opportunistic infections within the last 12 months.
- •Has prior therapy for AL amyloidosis or MM, with the exception of 160 mg dexamethasone (or equivalent corticosteroid) maximum exposure prior to enrollment.
- •Has received any live or live-attenuated vaccine within 30 days prior to first dose of belantamab mafodotin.
- •Is currently enrolled or has participated in any other clinical study involving an investigational study intervention or any other type of interventional medical research within 28 days before enrollment.
- •Has an ALT value >2.5xULN or >3xULN if hepatic involvement of AL amyloidosis (see Section 8.2.2.1).
- •Has a total bilirubin value >1.5xULN.
- •Has IgM-related AL amyloidosis.
- •Has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice.
- •Has documented presence of HBsAg and/or HBcAb at screening or within 3 months prior to the first dose of study intervention. Exceptions are detailed in Protocol Section 5.2.
- •Has a positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study intervention unless the participant can meet the following criteria: − RNA test negative. − Successful antiviral treatment (usually 8 weeks duration) is required, followed by a negative HCV RNA test after washout period of at least 4 weeks.
- •Chronic hepatitis B infection, with the presence of HBsAg and/or detectable HBV DNA, and hepatitis D co-infection, with hepatitis D antibody and/or RNA, within 3 months.
- •Has known urinary outflow obstruction.
- •25: Has acute diffuse infiltrative pulmonary and pericardial disease.
- •Has any form of non-AL amyloidosis, including wild type or mutated (ATTR) amyloidosis.
- •Has evidence of significant Cardiovascular conditions as specified in the Protocol Section 5.2.
- •Has Mayo stage 3B disease.
- •Has a current corneal epithelial disease except for mild punctate keratopathy.
- •Has previous or concurrent malignancies other than AL amyloidosis, except for any other malignancy that has been considered medically stable for at least 2 years, after discussion with GSK medical monitor. The participant must not be receiving active therapy, other than hormonal therapy for this disease.
- •Has major surgery within 2 weeks prior to the first dose of study interventions or has not recovered fully from surgery.
- •Has any history of prior allogenic or autologous BM transplant or other solid organ transplant.
研究组 & 干预措施
Endoxan®, ENDOXAN 50 mg, comprimé enrobé
Test
干预措施: Endoxan® (Drug)
Endoxan®, ENDOXAN 50 mg, comprimé enrobé
Test
干预措施: ENDOXAN 50 mg, comprimé enrobé (Drug)
Dexamethason 8 mg GALEN® Tabletten, Fortecortin® 2 mg Tabletten
Test
干预措施: Dexamethason 8 mg GALEN® Tabletten (Drug)
Dexamethason 8 mg GALEN® Tabletten, Fortecortin® 2 mg Tabletten
Test
干预措施: Fortecortin® 2 mg Tabletten (Drug)
VELCADE 3.5 mg powder for solution for injection, Bortezomib Hikma 3,5 mg Pulver zur Herstellung einer Injektionslösung
Test
干预措施: VELCADE 3.5 mg powder for solution for injection (Drug)
VELCADE 3.5 mg powder for solution for injection, Bortezomib Hikma 3,5 mg Pulver zur Herstellung einer Injektionslösung
Test
干预措施: Bortezomib Hikma 3,5 mg Pulver zur Herstellung einer Injektionslösung (Drug)
结局指标
主要结局
Overall Complete Hematologic Response (CHR) rate, defined as the proportion of participants who achieve a CHR, according to the consensus guidelines for AL amyloidosis, during or after study treatment initiation.
Overall Complete Hematologic Response (CHR) rate, defined as the proportion of participants who achieve a CHR, according to the consensus guidelines for AL amyloidosis, during or after study treatment initiation.
次要结局
- Incidence of adverse events (AEs), Serious adverse event (SAEs), and clinically significant changes in laboratory parameters.
- Incidence, severity, duration and resolution of ocular findings on ophthalmic examination (corneal examination findings and changes in Best corrected visual acuity [BCVA]).
- Organ response rate (OrRR) for kidney, heart, and/or liver defined as the proportion of baseline organ involved participants who achieve confirmed organ response in each corresponding organ.
- Duration of CHR defined as the time between the date of initial documentation of CHR to the date of first documented evidence of hematologic progressive disease (PD).
- Derived PK parameter (e.g., Cmax, AUC) values for belantamab mafodotin and Cysteine maleimidocaproyl monomethyl auristatin F (cys-mcMMAF), as data permit.
- Anti-drug antibody (ADA) incidence and summary titers of ADAs against belantamab mafodotin.
研究者
EU GSK Clinical Trials Call Center
Scientific
Glaxosmithkline Research & Development Limited
研究点 (10)
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