2025-523117-28-00招募中2 期
A Phase 2, multicenter, open label, non-randomized study to evaluate the efficacy and safety of extended dosing of belantamab mafodotin in different combinations with standard of care regimens in participants with relapsed-refractory multiple myeloma (DREAMM-15)
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
- 45
- 试验地点
- 31
- 主要终点
- ORR, defined as the percentage of participants with a confirmed PR or better (i.e., PR, VGPR, CR, sCR).
研究概览
简要总结
To assess the response rate in RRMM participants to BPd or BVd or BKd combination therapy using an extended dosing schedule.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •INC#1 Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
- •INC#10 Female patients: Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •INC#11 Male patients: Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •INC#2 Male or female, 18 years or older (at the time consent is obtained).
- •INC#3 Have a confirmed diagnosis of MM as defined by the IMWG criteria.
- •INC#4 BPd and BKd: ECOG performance status of zero to 2; INC#4 BVd: Previously treated with at least 1, but no more than 2, prior lines of MM therapy and must have documented disease progression during or after their most recent therapy.
- •INC#5 BPd: Have been previously treated with at least 1, but no more than 2, prior lines of MM therapy including a lenalidomide-containing regimen (lenalidomide must have been administered for at least 2 consecutive cycles) and must have documented disease progression during or after their most recent therapy. INC#5 BVd ECOG performance status of zero to
- •INC#5 BKd:Previously treated with at least 1, but no more than 2, prior lines of MM therapy and must have documented disease progression during or after their most recent therapy.
- •INC#6 BPd and BKd: Must have at least 1 aspect of measurable disease, defined as one the following: a. Urine M-protein excretion ≥200 mg/24 h, or b. Serum M-protein concentration ≥0.5 g/dL (≥5.0 g/L), or c. Serum FLC assay: involved FLC level ≥10 mg/dL (≥100 mg/L) and an abnormal serum free light chain ratio (<0.26 or >1.65) only if patient has no measurable urine or serum M spike. INC#6 BVd: Patients with a history of ASCT are eligible for study participation provided the following eligibility criteria are met: a. ASCT was >100 days prior to initiating study treatment, and b. No active bacterial, viral, or fungal infection(s) present.
- •INC#7 BPd and BKd: Patients with a history of ASCT are eligible for study participation provided the following eligibility criteria are met: a. ASCT was >100 days prior to the first dose of study medication, b. No active bacterial, viral, or fungal infection(s) present. INC#7 BVd: Must have at least 1 aspect of measurable disease, defined as one the following: a. Urine M-protein excretion ≥200 mg/24h, or b. Serum M-protein concentration ≥0.5 g/dL (≥5.0 g/L), or c. Serum FLC assay: involved FLC level ≥10 mg/dL (≥100 mg/L) and an abnormal serum free light chain ratio (<0.26 or >1.65) only if patient has no measurable urine or serum M spike.
- •INC#8: All prior treatment-related toxicities (defined by NCI-CTCAE v5.0) must be Grade ≤1 at the time of enrollment, except for alopecia.
- •INC#9: Adequate organ system functions as defined by the laboratory assessments listed in the 224317 Protocol.
排除标准
- •EXC#1 BPd: Active plasma cell leukemia at Screening. Symptomatic amyloidosis, active POEMS syndrome EXC#1 Bvd: Intolerant to bortezomib, or refractory to bortezomib EXC#1 Bkd: Intolerant to carfilzomib, or refractory to carfilzomib
- •EXC #18 BPd: Received prior BCMA targeted therapy. EXC#18 Bvd: Is currently enrolled or has participated in any other clinical study involving an investigational drug within 30 days or 5 half-lives (whichever is shorter) preceding the first dose of study intervention. EXC #18 BKd: Received prior BCMA targeted therapy.
- •EXC #19 BPd, BKd: Is currently enrolled or has participated in any other clinical study involving an investigational drug within 30 days or 5 half-lives (whichever is shorter) preceding the first dose of study intervention. EXC#19 BVd: Known HIV infection, unless the participant can meet all of the criteria mentioned in the protocol.
- •EXC#10 BPd: Contraindications to or unwilling to undergo protocol-required antithrombotic prophylaxis. EXC#10 BVd, BKd: Current or prior clinically significant ILD or confirmed past diagnosis of PML.
- •EXC #20 BPd, BKd: Known HIV infection, unless the participant can meet all of the criteria mentioned in the protocol. EXC #20 BVd: Pregnant or lactating female.
- •EXC #21 BPd, BKd: Pregnant or lactating female. EXC#21 BVd: Has an ALT value >2.5x ULN.
- •EXC #22 BPd, BKd: Has an ALT value >2.5x ULN. EXC#22 BVd: Has a total bilirubin value >1.5x ULN.
- •EXC #23 BPd, BKd: Has a total bilirubin value >1.5x ULN. EXC#23 BVd: Has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice.
- •EXC #24 BPd, BKd: Has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice. EXC#24 BVd: Has a positive HCV antibody test result at screening or within 3 months prior to the first dose of study intervention unless HCV RNA is negative, indicating past resolved HCV infection, including participants who have undergone curative treatment.
- •EXC #25 BPd, BKd: Has a positive HCV antibody test result at screening or within 3 months prior to the first dose of study intervention unless HCV RNA is negative, indicating past resolved HCV infection, including participants who have undergone curative treatment. EXC#25 Bvd: Has a positive HCV RNA test result at screening or within 3 months prior to the first dose of study intervention.
- •EXC #26 BPd, BKd: Has a positive HCV RNA test result at screening or within 3 months prior to the first dose of study intervention. EXC#26 Bvd: Has documented presence of HBsAg and/or HBcAb at screening or within 3 months prior to the first dose of study intervention. Participants with hepatitis B will be excluded unless the protocol criteria can be met.
- •EXC#3 BPd: Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to belantamab mafodotin or drugs chemically related to belantamab mafodotin, or any of the components of the study treatment. EXC#3 BVd, BKd: Previous or concurrent invasive malignancy other than MM
- •EXC #27 BPd, BKd: Has documented presence of HBsAg and/or HBcAb at screening or within 3 months prior to the first dose of study intervention. Participants with hepatitis B will be excluded unless the protocol criteria can be met. EXC#27 Bvd: Evidence of cardiovascular risk.
- •EXC #28 BPd, BKd: Evidence of cardiovascular risk. EXC #28 BVd: Has QTc >450 msec or QTc >480 msec for participants with bundle branch block.
- •EXC #29 BPd: Has QTc >450 msec or QTc >480 msec for participants with bundle branch block. EXC #29 BKd: Pericardial disease, including pericarditis, pericardial effusion, cardiac tamponade, and constrictive pericarditis, as assessed by ECG abnormalities, echocardiography, chest X-ray, and/or computed tomography /magnetic resonance imaging (as indicated).
- •EXC#11 BPd: Current or prior clinically significant ILD or confirmed past diagnosis of PML. EXC#11 BVd, Bkd: Current corneal epithelial disease except for mild punctate keratopathy.
- •EXC#12 BPd: Current corneal epithelial disease except for mild punctate keratopathy. EXC#12 BVd: Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain. EXC #12 BKd: Pleural effusions requiring thoracentesis within 14 days prior to enrollment; Ascites requiring paracentesis within 14 days prior to enrollment; Intolerance to hydration due to pre-existing pulmonary or cardiac impairment; Known pulmonary hypertension.
- •EXC#13 BPd: Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including laboratory abnormalities) that could interfere with participant’s safety, obtaining informed consent or compliance to the study procedures. EXC#13 BVd: Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including laboratory abnormalities) that could interfere with participant’s safety, obtaining informed consent or compliance to the study procedures. EXC #13 BKd: Known history of allergy to captisol (i.e., a cyclodextrin) derivatives used to solubilize carfilzomib.
- •EXC #14 BPd: Patients after prior allogeneic stem cell transplant. EXC#14 BVd: Patients after prior allogeneic stem cell transplant. EXC #14 BKd: Any serious and/or 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.
- •EXC #15 BPd: Systemic anti-myeloma therapy (including chemotherapy and systemic steroids); prior treatment with an anti-MM monoclonal antibody drug within 30 days of receiving the first dose of study intervention. EXC#15 BVd: Systemic anti-myeloma therapy (including chemotherapy and systemic steroids); prior treatment with an anti-MM monoclonal antibody drug within 30 days of receiving the first dose of study intervention. EXC #15 BKd: Patients after prior allogeneic stem cell transplant.
- •EXC #16 BPd, Plasmapheresis within 7 days prior to the first dose of study intervention. EXC#16 BVd: Plasmapheresis within 7 days prior to the first dose of study intervention. EXC #16 BKd: Systemic anti-myeloma therapy (including chemotherapy and systemic steroids); prior treatment with an anti-MM monoclonal antibody drug within 30 days of receiving the first dose of study intervention.
- •EXC#2 BPd: Previous or concurrent invasive malignancy other than MM EXC#2 BVd, BKd: Active plasma cell leukemia at Screening. Symptomatic amyloidosis, active POEMS syndrome.
- •EXC#4 BPd: Evidence of active mucosal or internal bleeding. EXC#4 BVd: Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin, bortezomib, boron or mannitol or any other components of the study intervention. EXC#4 BKd: Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to any components of the study intervention.
- •EXC #30 BKd: Has QTc >450 msec or QTc >480 msec for participants with bundle branch block.
- •EXC#5 BPd: Active infection within 14 days prior to enrollment requiring systemic antibiotics, antiviral (except antiviral therapy directed at hepatitis B) or antifungal agents. Such infection must be fully resolved prior to initiating study intervention. EXC#5 BVd, BKd: Evidence of active mucosal or internal bleeding.
- •EXC#6 BPd: Any major surgery within 4 weeks prior to the first dose of study drug. Exception allowed for bone stabilizing surgery after consultation with Medical Monitor. EXC#6 Bvd, BKd: Active infection within 14 days prior to enrollment requiring systemic antibiotics, antiviral (except antiviral therapy directed at hepatitis B) or antifungal agents. Such infection must be fully resolved prior to initiating study intervention.
- •EXC#7 BPd: Intolerance or contraindications to anti-viral prophylaxis. EXC#7 BVd, BKd: Any major surgery within 4 weeks prior to the first dose of study drug. Exception allowed for bone stabilizing surgery after consultation with Medical Monitor.
- •EXC#8 BPd: Presence of active renal conditions. Patients with isolated proteinuria resulting from MM are eligible, provided they fulfill criteria given in the protocol. EXC#8 BVd, BKd: Intolerance or contraindications to anti-viral prophylaxis.
- •EXC#9 BPd: Active or history of venous and arterial thromboembolism within the past 3 months. EXC#9 BVd, BKd: Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect participant’s safety). Patients with isolated proteinuria resulting from MM are eligible, provided they fulfill criteria given in the protocol.
- •EXC #17 BPd: Received prior treatment with or intolerant to pomalidomide. EXC#17 BVd: Received prior BCMA targeted therapy. EXC #17 BKd: Plasmapheresis within 7 days prior to the first dose of study intervention.
研究组 & 干预措施
POMALIDOMIDE, POMALIDOMIDE, POMALIDOMIDE, POMALIDOMIDE
Comparator
干预措施: POMALIDOMIDE (Drug)
BORTEZOMIB
Comparator
干预措施: BORTEZOMIB (Drug)
DEXAMETHASONE, DEXAMETHASONE
Comparator
干预措施: DEXAMETHASONE (Drug)
CARFILZOMIB, CARFILZOMIB, CARFILZOMIB
Comparator
干预措施: CARFILZOMIB (Drug)
结局指标
主要结局
ORR, defined as the percentage of participants with a confirmed PR or better (i.e., PR, VGPR, CR, sCR).
ORR, defined as the percentage of participants with a confirmed PR or better (i.e., PR, VGPR, CR, sCR).
次要结局
- • CRR, defined as the percentage of participants with a confirmed CR or better. • MRD negativity rate, defined as the percentage of participants who achieve MRD negative status at least once during the time of confirmed CR or better response as per IMWG. • DoR, defined as the time from first documented evidence of PR or better until PD or death due to any cause.
- • Incidence and severity of AEs and SAEs; • Incidence of AEs leading to dose modifications or study intervention discontinuation; • Incidence and severity of ocular findings on ophthalmic exam (changes in VA and cornea findings).
- OSDI, PRO-CTCAE (ocular), PROSIM-Q, and CTCAEs (eye disorders – other) concordance with KVA
研究者
EU GSK Clinical Trials Call Center
Scientific
Glaxosmithkline Research & Development Limited
研究点 (31)
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