NCT06510491招募中2 期
A Phase 2 Trial Investigating Epcoritamab in Patients With Previously Treated Waldenstrom Macroglobulinemia (WM)
Gottfried von Keudell, MD PhD3 个研究点 分布在 1 个国家目标入组 20 人开始时间: 2024年12月6日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 3
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
This study is being done to determine if epcoritamab can be used to treat participants with previously treated Waldenstrom Macroglobulinemia (WM).
The names of the study drug involved in this study is:
-Epcoritamab (a type of antibody)
详细描述
This is a prospective phase 2, single arm, open label trial to determine if epcoritamab can be used to treat participants with previously treated Waldenstrom Macroglobulinemia (WM). Epcoritamab is a bispecific antibody, a synthetic protein that activates the immune system to target cancer cells.
The U.S. Food and Drug Administration (FDA) has not approved epcoritamab for WM.
The research study procedures include screening for eligibility, in-clinic visits, questionnaires, blood tests, electrocardiograms, bone marrow biopsies, and Computerized Tomography (CT) scans.
Participants will receive study treatment for up to 4 months and will be followed for 24 months.
It is expected that about 20 people will take part in this research study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •A diagnosis of lymphoplasmacytic lymphoma/WM that is CD20+ by immunophenotype or immunohistochemistry confirmed by bone marrow biopsy/aspirate (fresh or archival tissue acceptable) at time of most recent progression. All degrees of CD20 positivity will be accepted.
- •Serum IgM level >2x upper limit of normal (ULN)
- •Meeting criteria for initiation of treatment per IWWM2 criteria [Kyle Semin Oncol 2002], including but not limited to hyperviscosity syndrome, peripheral neuropathy, cold agglutinin disease, cryoglobulinemia, amyloidosis, cytopenias due to bone marrow infiltration, symptomatic or bulky lymph nodes, symptomatic splenomegaly, constitutional symptoms not otherwise explained by other causes, signs of organ dysfunction secondary to WM
- •At least one prior line of treatment that was discontinued either due to intolerance or disease progression
- •Prior therapies must have included an anti-CD20 antibody (e.g. rituximab) and a BTK inhibitor (e.g. ibrutinib, zanubrutinib). Patients who received ibrutinib and rituximab in combination as first line therapy will be eligible. BTKi should be stopped to allow a washout period of no less than 4 half-lives prior to epcoritamab.
- •Age ≥18 years
- •ECOG performance status £ 2
- •Life expectancy of greater than 2 years
- •Participants must meet the following organ and marrow function as defined below:
- •absolute neutrophil count ≥1000 cells/mcl (G-CSF allowed)
- •absolute lymphocyte count ≥200 cells/mcl
- •platelets ≥75,000 cells/mcl OR ≥50,000 cells/mcl in the presence of bone marrow involvement or splenomegaly (Note: no PLT transfusions within 7 days prior to screening)
- •hemoglobin ≥ 8 g/dL (transfusion allowed)
- •total bilirubin ≤ 1.5 institutional upper limit of normal (ULN). In patients with suspected/known Gilbert's disease total bilirubin up to 3x ULN will be allowed but direct bilirubin must be ≤ 2 x ULN
- •AST(SGOT)/ALT(SGPT) ≤3× institutional ULN
- •creatinine ≤ institutional ULN OR
- •creatinine clearance >45 ml/min (by Cockcroft-Gault estimate or 24-hr creatinine clearance measurement)
- •Subject does not have an active (PCR-positive) Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection. If laboratory evidence for a chronic infection with hepatitis B, close monitoring and prophylactic therapy is required as described in Section 5.
- •Participants with a history of prior malignancy will be eligible if all treatment of that malignancy was completed at least 2 years before registration, the treatment was considered "curable-intent", and there is no evidence of disease.
- •Ability to understand and the willingness to sign a written informed consent document.
- •Females of childbearing potential must agree to practice a highly effective method of birth control (as defined by the EU Clinical Trial Facilitation Group) consistent with local regulations regarding the use of birth control methods for patients participating in clinical trials:
- •Established use of oral, injected or implanted combined (estradiol and progesterone containing) hormonal contraception;
- •Placement of an intrauterine device (IUD) or intrauterine system (IUS);
- •Male partner sterilization (the vasectomized partner should be the sole partner for that patient)
- •True abstinence (when this is in line with the preferred and usual lifestyle of the patient)
- •Women must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the trial and for 12 months after receiving the last dose of epcoritamab. Men must also not donate sperm during the trial and for 12 months after receiving the last dose of epcoritamab.
- •A man who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control (i.e. use of condom) during the trial and for 12 months after receiving the last dose of epcoritamab.
- •Patients with HIV may be enrolled if they are on stable antiretroviral therapy, have an undetectable viral load, and CD4 count > 250 cells/mm3.
排除标准
- •Participants who have disease that has transformed to aggressive lymphoma
- •Participants with symptomatic or suspected hyperviscosity syndrome or IgM levels greater than 4000 mg/dL who are unable to undergo plasmapheresis to decrease the risk of an IgM flare. Participants who can undergo plasmapheresis will be eligible as long as they undergo the procedure prior to first treatment dose.
- •Participants who are receiving any other investigational agent
- •Washout from prior therapy: BTKi: no less than5 half-lives prior to epcoritamab to prevent BTKi rebound and rituximab: no less than 4 weeks (28 days) from last dose.
- •Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1) except for alopecia and peripheral neuropathy
- •Uncontrolled intercurrent active infection requiring hospitalization or intravenous antimicrobial agents within 4 weeks of start of treatment
- •Uncontrolled underlying cardiac conditions including but not limited to: congestive heart failure grade III or IV (by NYHA) or EF < 45%, unstable angina pectoris, acute myocardial infarction < 6 months, uncontrolled cardiac arrhythmia
- •History of uncontrolled neurologic condition including but not limited to: seizure disorder, stroke, psychosis, dementia, CNS vasculitis, encephalitis
- •Need for supplemental O2 at rest to maintain SaO2>92%
- •Chronic immunosuppressive therapy for non-WM-related indication within 28 days of initiation of treatment, including systemic corticosteroids 20 mg/day or greater prednisone-equivalent
- •Patients with known or suspected CNS involvement or leptomeningeal disease (i.e. BingNeel Syndrome) are excluded given concern for potentially increased risk of neurologic toxicity with epcoritamab. Patients with history of CNS malignancy from separate malignancy must have completed CNS-directed therapy and must currently have no evidence of disease
- •Pregnant or breastfeeding women or participants unwilling to adhere to institutional guidelines for highly effective contraception for the duration of the therapy are excluded. This is because of the unknown but potential risk of teratogenic or abortifacient effects, as well as potential for adverse events in nursing infants secondary to treatment of the mother, as epcoritamab has not yet been studied in this patient population. A female can be determined to not be of childbearing potential if she meets any of the following criteria:
- •Premenarchal
- •Postmenopausal (>45 years of age with amenorrhea for at least 12 months or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone [FSH] level >40 IU/L or mIU/mL)
- •Permanently sterilized (e.g., bilateral tubal occlusion [which includes tubal ligation procedures as consistent with local regulations], hysterectomy, bilateral salpingectomy, bilateral oophorectomy) Note: If the childbearing potential changes after start of the trial (e.g., woman who is not heterosexually active becomes active, premenarchal woman experiences menarche) a woman must begin a highly effective method of birth control, as described under 3.1.
- •Known current alcohol or drug abuse, psychiatric illness, or unstable social situation that is likely to limit compliance with study requirements
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to epcoritamab
- •Exposure to a live or a live attenuated vaccine within 4 weeks
研究组 & 干预措施
Safety Lead-In Epcoritamab
Experimental
Participants will be enrolled using a modified 3+3 dose-escalation design to establish the Recommended Phase 2 Dose of Epcoritamab and will complete study procedures as follows:
- Baseline visit with CT scan and bone marrow biopsy.
- Bone marrow biopsy before cycle 6.
- Cycles 1 - 3:
--Days 1, 8, 15, and 22 of 28 day cycle: Predetermined dose of Epcoritamab 1x daily.
- Cycles 4 - 9:
--Days 1 and 15 of 28 day cycle: Predetermined dose of Epcoritamab 1x daily.
- Cycles 10 - 12:
--Day 1 of 28 day cycle: Predetermined dose of Epcoritamab 1x daily.
- End of Treatment visit with CT scan and bone marrow biopsy.
- Follow up visits: every 3 months for 2 years
- Off study visit
- If there are 0 out of 3 dose-limiting toxicities (DLTs), the study will proceed to phase II. If 1/3 participants experience a DLT, up to 3 additional participants will be treated at the same dose level. If more than 1/6 total participants experience a DLT, then the study will not proceed to phase 2.
干预措施: Epcoritamab (Drug)
Phase II Epcoritamab
Experimental
Participants will be enrolled and will complete study procedures as follows:
- Baseline visit with CT scan and bone marrow biopsy.
- Bone marrow biopsy before cycle 6.
- Cycles 1 - 3:
--Days 1, 8, 15, and 22 of 28 day cycle: Predetermined dose of Epcoritamab 1x daily.
- Cycles 4 - 9:
--Days 1 and 15 of 28 day cycle: Predetermined dose of Epcoritamab 1x daily.
- Cycles 10 - 12:
--Day 1 of 28 day cycle: Predetermined dose of Epcoritamab 1x daily.
- End of Treatment visit with CT scan and bone marrow biopsy.
- Follow up visits: every 3 months for 2 years
- Off study visit
干预措施: Epcoritamab (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: Up to 12 cycles of treatment (28 days per cycle)
The overall response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on modified IWWM6 criteria.
次要结局
- Median Time to Next Line of Therapy (TTNT)(Up to 2 years)
- Median Duration of Overall Response (DOR)(Up to 12 cycles of treatment (28 days per cycle))
- Median Time to Best Response(Up to 12 cycles of treatment (28 days per cycle))
- 6-month Best Response Rate(6 months)
- Major Response Rate (MRR)(Up to 12 cycles of treatment (28 days per cycle))
- 2-year Progression-Free Survival (PFS) Rate(2 years)
- 2-year Overall Survival (OS)(2 years)
- Grade 3-5 Treatment-related Toxicity Rate(Up to 12 cycles of treatment (28 days per cycle))
研究者
Gottfried von Keudell, MD PhD
Sponsor Investigator
Beth Israel Deaconess Medical Center
研究点 (3)
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