Study of Isatuximab Plus Pomalidomide and Dexamethasone in Highly Toxicity-vulnerable Subjects With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 6
- 试验地点
- 4
- 主要终点
- Overall response Rate (ORR)
研究概览
简要总结
This research study aims to evaluate the safety and effectiveness of the combination of isatuximab, pomalidomide, and dexamethasone (Isa-Pd) for the treatment of relapsed or refractory multiple myeloma (RRMM), which refers to multiple myeloma that has returned or has not responded to prior treatment. The study will specifically investigate the impact of administering lower-than-standard doses of pomalidomide and dexamethasone. Using lower doses of pomalidomide and dexamethasone in this setting has not been approved by the Food and Drug Administration (FDA).
详细描述
This study aims to address the challenges faced in selecting appropriate therapy for elderly or highly toxicity-vulnerable patients who are poor candidates for standard (full-dose) chemotherapy regimens. Traditional clinical trials often exclude these patients, limiting the generalizability of available data. This single-arm multicenter phase II study will enroll 49 older and/or toxicity-vulnerable patients with RRMM. The study will evaluate the safety and effectiveness of isatuximab when used in combination with pomalidomide and dexamethasone at lower than standard doses. The primary objective is to estimate the overall response rate (ORR), while secondary objectives include the estimation of additional measures of response, as well as measures of toxicity and tolerability. All participants in the trial will also be evaluated by Cancer and Aging Research Group Geriatric Assessments (CARG-GA) and patient- reported outcome (PRO) measures of quality of life (QOL). Biomarkers of aging and frailty will also be studied.
Duration of therapy:
The duration of study participation will depend on the response to the treatment. In the absence of treatment delays due to adverse events, treatment with Isa-Pd will generally continue until disease progression, unacceptable side effects, other illness or condition that prevents further study treatment, or a subject's decision to withdraw from the study. On average, subjects will most likely be treated for approximately 10 months on this study.
Duration of Follow-Up:
All participants, including those withdrawn for adverse events (AEs) will be followed after removal from study treatment until death or full subject withdrawal from the study for other reasons. Participants removed from the study treatment for unacceptable AEs will be followed for resolution or stabilization of the AEs.
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
- •Written informed consent obtained to participate in the study and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information (PHI). Consent must be obtained before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- •Age ≥ 18 years at the time of consent.
- •Documented symptomatic multiple myeloma that has previously responded to therapy (partial response or better) and is relapsed or relapsed and refractory to the last line of therapy.
- •Patients must also be refractory to at least one prior line of therapy that includes an IMiD and/or a PI, and should have received at least 2 cycles of that regimen to be evaluable for refractoriness .
- •If previously treated with an anti-CD38 containing regimen, the subject must have achieved at least a PR to that line of therapy and must not have received an anti- CD38 mAb for at least 6 months prior to enrollment.
- •Willing and able to adhere to the study visit schedule and other protocol requirements based on the judgement of the investigator.
- •Predicted high risk for severe toxicity from intensive regimens for RRMM, such as standard (full-dose) DPD, DVD, KPD, KRD, Ixa-PD, or Elo-PD as each regimen was published (such regimens often use, for example, twice-weekly bortezomib at 1.3 mg/m2, lenalidomide at 25 mg, or pomalidomide 4 mg). High-risk is defined as one of the following:
- •A. Score ≥ 2 (indicating "frail") on the International Myeloma Working Group instrument (IMWG; Palumbo et al. [Blood 2015]) B.KPS ≤ 70
- •C. Not meeting criteria A or B above but felt by treating clinician to not be a candidate for a standard full-dose regimen on account of one of the following:
- •i) History of clinically significant non-hematologic grade ≥3 (NCI CTCAE, version 5.0) toxicity attributed to prior anticancer therapy ii) History of requiring dose-reduction of at least two separate anticancer drugs during prior therapy for multiple myeloma.
排除标准
- •All subjects meeting any of the listed exclusion criteria at baseline with be excluded from study participation.
- •Anti-myeloma treatment within 2 weeks of cycle 1 day 1
- •Prior treatment with pomalidomide
- •Any monoclonal antibody therapy within the previous 30-days
- •Anti-CD38 monoclonal antibody therapy within the previous 6 months
- •Autologous stem cell transplantation within 12 weeks of day 1 of cycle 1
- •Subjects felt to not be candidates by treating physician for any systemic therapy due to excessive comorbidities, frailty, impaired performance status, or other severe limitations. Such limitations can be conceptualized generally as making subjects exceedingly high risk for any systemic treatment. These limitations often stem from medical comorbidities unrelated to MM and they are hence unlikely to improve with MM therapy.
研究组 & 干预措施
Single Arm
Subjects with relapsed or refractory multiple myeloma receiving the study treatment.
干预措施: Isatuximab (Drug)
Single Arm
Subjects with relapsed or refractory multiple myeloma receiving the study treatment.
干预措施: Pomalidomide (Drug)
Single Arm
Subjects with relapsed or refractory multiple myeloma receiving the study treatment.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Overall response Rate (ORR)
时间窗: Up to 12 weeks
ORR is defined as a partial response or better (≥PR) to study therapy at any time, based on International Myeloma Working Group (IMWG) criteria. Complete response (CR): Negative immunofixation of serum and urine, disappearance of soft tissue plasmacytomas, and \<5% plasma cells in bone marrow (BM). Stringent complete response(sCR): CR plus normal free light chains (FLC) ratio and absence of clonal plasma cells in BM biopsy. Very good partial response (VGPR):-Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M component plus urine M component \<100/24h. Partial response (PR) ≥50% reduction of serum M-protein \& reduction in 24-hour (24h) urinary M-protein by ≥90% or to \<200 mg/24h and if present at baseline, a ≥ 50% reduction in the size soft tissue plasmacytomas.
Overall Response Rate (ORR)
时间窗: Up to 12 weeks
Overall response rate (ORR) is defined as the percentage of participants achieving a partial response or better (≥PR) per IMWG criteria. The number and percentage of participants achieving at least a partial response were reported. Complete response (CR) requires negative serum and urine immunofixation, disappearance of plasmacytomas, and \<5% bone marrow plasma cells; stringent complete response (sCR) requires CR plus a normal free light chain ratio and no clonal plasma cells in bone marrow. Very good partial response (VGPR) is defined as M-protein detectable by immunofixation but not electrophoresis, or a ≥90% reduction in serum M-protein with urine M-protein \<100 mg/24h. Partial response (PR) is defined as a ≥50% reduction in serum M-protein and a ≥90% reduction in 24-hour urine M-protein (or to \<200 mg/24h), with a ≥50% reduction in plasmacytomas if present at baseline.
次要结局
- Treatment failure-free survival (TFFS)(Up to 3 years)
- Bone marrow minimal residual disease (MRD) negativity(Up to 12 weeks)
- Overall survival(Up to 3 years)
- Treatment related adverse events rate(Up to 12 weeks)
- Maximum depth of response(Up to 12 weeks)
- Time to best response(Up to 12 weeks)
- Median time to next treatment (TTNT)(Up to 3 years)
- Clinical benefit rate (CBR)(Up to 12 weeks)
- Time to first response(Up to 12 weeks)
- Duration of response(Up to 3 years)
- Progression-free survival (PFS)(Up to 3 years)
- Treatment Related Adverse Events Rate(Up to 12 weeks)
- Treatment Failure-free Survival (TFFS)(Up to 3 years)
- Maximum Depth of Response(Up to 12 weeks)
- Clinical Benefit Rate (CBR)(Up to 12 weeks)
- Bone Marrow Minimal Residual Disease (MRD) Negativity(Up to 12 weeks)
- Time to First Response(Up to 12 weeks)
- Time to Best Response(Up to 12 weeks)
- Duration of Response(Up to 3 years)
- Progression-free Survival (PFS)(Up to 3 years)
- Median Time to Next Treatment (TTNT)(Up to 3 years)
- Overall Survival(Up to 3 years)