A Study of Elranatamab Management With Outpatient and Intermittent Dosing in Relapsed/Refractory Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 9
- 主要终点
- Hospitalization rate
研究概览
简要总结
A phase II study of single agent elranatamab in patients with relapsed and/or refractory multiple myeloma (MM) who have previously received at least three classes of therapeutic agents and are refractory to the last line of treatment. The primary objective of this study is to improve the tolerability and safety of elranatamab in patients with relapsed and/or refractory multiple myeloma by evaluating an outpatient and intermittent dosing strategy.
详细描述
This is a multi-centre, single arm, phase II study of single agent elranatamab in patients with relapsed and/or refractory multiple myeloma (MM) who have previously received at least three classes of therapeutic agents and are refractory to the last line of treatment. Potential study participants must have documented evidence of refractory or progressive disease during or within 60 days (measured from the end of the last cycle) of completing treatment with the last anti-myeloma drug regimen used just prior to study entry. Study participants will receive SC administration of elranatamab until disease progression, unacceptable toxicity or death. The primary short term outcome is hospitalization rate within the first 2 weeks of Cycle 1 of treatment; the primary long term outcome is rate of grade 3+ infections within the first 24 months of treatment. Study participants will be followed for survival for 36 months from the date of enrollment. A total of 40 study participants will be enrolled across approximately 5 Canadian clinical trial sites.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Relapsed and/or refractory MM defined as:
- •Documented evidence of progressive disease (PD) after achieving at least minimal response (MR) for ≥ 1 cycle during a previous MM treatment (i.e., relapsed MM).
- •Disease progression during or within 60 days from the end of the most recent MM treatment (i.e., refractory MM).
- •Measurable disease based on IMWG criteria, defined as at least one of the following, documented within 28 days before enrollment:
- •Serum M-protein ≥ 0.5 g/dl.
- •Urine M-protein excretion ≥ 200 mg/24 h.
- •Serum-free light chains (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 for patients without measurable serum or urine M protein.
- •Receipt of at least three prior classes of drugs either in separate regimens or as combinations.
- •The three classes are defined as:
- •An immunomodulatory drug (lenalidomide or pomalidomide), a proteasome inhibitor (bortezomib, ixazomib, carfilzomib), and an anti-CD38 drug (daratumumab or isatuximab).
- •At least 18 years of age.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of ≤2.
排除标准
- •Medical conditions
- •Active plasma cell leukemia (either 20% of peripheral white blood cells or > 2.0 × 109/L circulating plasma cells by standard differential).
- •Amyloidosis.
- •POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal plasma cell disorder, Skin Changes).
- •Monoclonal gammopathy of unknown significance or smoldering multiple myeloma.
- •Solitary plasmacytoma.
- •Stem cell transplant within 12 weeks prior to enrollment or active graft versus host disease.
- •History of prior treatment with a BCMA targeting agent.
- •Laboratory Parameters
- •Laboratory results within 28 days as per below prior to enrollment:
- •Absolute neutrophil count (ANC) ≤ 1.0 x 109 /L) (use of growth factor is permitted if completed at least 7 days prior to enrollment).
- •Platelet count ≤ 25 x 109 /L (transfusion support permitted if completed at least 7 days prior to enrollment).
- •Hemoglobin ≤ 8.0 g/dL (transfusion support permitted if completed at least 7 days prior to enrollment, concurrent erythropoietin stimulating agents allowed).
- •Serum AST and ALT > 2.5 x upper limit of normal (ULN).
- •Creatinine clearance < 30 mL/min (according to the Cockcroft Gault formula, by 24-hour urine collection for creatinine clearance, or according to local institutional standard method).
- •Total bilirubin > 2.0 x ULN (≥ 3.0 unless known to have Gilbert's disease).
- •Support Requirement
- •As this protocol requires outpatient administration, the patient will be excluded if they cannot agree to the following for the first 9 days post-first dose of drug administration:
- •Staying within 60 minutes of travel distance to their trial-based hospital.
- •Must have a caregiver/support person who will stay with the patient.
- •Patient and/or their caregiver/support person agree to monitor and record oral temperature q8 hours.
- •Patients must agree that if they have an oral temperature of (≥38°C), they must report to the study team within 1 hour and can come to the hospital for admission within 2 hours.
- •Other co-morbidities
- •Impaired cardiovascular function or clinically significant cardiovascular diseases, defined as any of the following within 6 months before enrollment:
- •Acute myocardial infarction or acute coronary syndromes (eg, unstable angina, coronary artery bypass graft, coronary angioplasty or stenting, symptomatic pericardial effusion).
- •Clinically significant cardiac arrhythmias (eg, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia).
- •Thromboembolic or cerebrovascular events (eg, transient ischemic attack, cerebrovascular accident, deep vein thrombosis [unless associated with a central venous access complication], or pulmonary embolism).
- •Prolonged QT syndrome (or triplicate average QTcF >470 msec at screening).
- •Ongoing Grade ≥2 peripheral sensory or motor neuropathy.
- •History of Guillain-Barre Syndrome (GBS) or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy.
- •Unresolved acute effects of any prior therapy for MM in the last three months to either baseline severity or NCI CTCAE ≤Grade
- •Active HBV, HCV, SARS-CoV2, HIV, or any active, uncontrolled bacterial, fungal, or viral infection.
- •Any other active malignancy within 2 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
- •Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormalities), or surgical (major surgery within 14 days prior to enrollment) that could interfere with the patient's safety, obtaining informed consent or compliance to the study procedures.
- •Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to elranatamab or any of the components of the study treatment.
- •Concomitant Medications
- •Treatment with a chemotherapeutic or anti-MM drug within the last 28 days or 5 half-lives (whichever is shorter) prior to enrollment or are currently enrolled in another interventional clinical study.
- •Receipt of any other therapy to treat cancer (including radiation, biologics, cellular therapies, and/or steroids at doses > 20 mg dexamethasone or equivalent) within 14 days prior to the enrollment.
- •Receipt of any live vaccine within 30 days prior to enrollment or expected need of live vaccination during study participation. (Administration of locally approved non-live vaccine can be done as per local guidelines during the screening and/or treatment period including the COVID-19 mRNA vaccine. Elranatamab should be administered ± 7 days from the SARS-CoV-2 vaccine administration).
- •Pregnancy and Contraception
- •Pregnancy or lactating female or inability of female patients of childbearing potential (FCBP) to meet contraception requirements (see Section 5.1.3.).
- •Informed Consent
- •Inability to provide signed, informed consent.
研究组 & 干预措施
Elranatamab injection
The administration of two step-up elranatamab doses (12 mg and 32 mg) and full dose 76 mg. The dosing interval for the first Cycle (each cycle q28 days) is every week. Cycles 2-3, the dosing interval increases to q2weeks. Cycles 4-12, the dosing interval increases to q4weeks. Cycles 13+, further dosing interval increases to q8weeks will be scheduled if a participant meets criteria for IMWG complete response (CR) in Cycle 12 (bone marrow required at Cycle 12 to confirm). If a participant does not meet CR criteria at Cycle 12, they will be continued on Q4W dosing.
干预措施: Elranatamab injection (Drug)
结局指标
主要结局
Hospitalization rate
时间窗: 2 weeks
Hospitalization rate, defined as the number of patients who are hospitalized within the first 2 weeks of Cycle 1 of treatment, due to any cause, divided by the number of patients who are treated with elranatamab.
Rate of grade 3+ infections
时间窗: 24 months
Rate of grade 3+ infections as grade by NCI CTCAE v5 within the first 24 months of treatment, defined as the number of patients who experience a grade 3+ infection within 24 months of treatment, divided by the number of patients who are treated with elranatamab.
次要结局
- Progression free survival.(36 months)
- Frequency and Timing of Hospitalization(2 weeks.)
- Patient Quality of Life(To the time of disease progression.)
- Time to response.(36 months)
- Adverse Events(36 months)
- Overall response rate.(36 months)
- Patient Frailty(To the time of disease progression.)
- Duration of response.(36 months)
- Clinical laboratory data(36 months.)
- Overall survival(36 months)