2025-522295-91-00招募中2 期
HOVON 178 WM: A prospective phase I/II trial of epcoritamab in patients with relapsed or refractory Waldenstrom’s macroglobulinemia
Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting7 个研究点 分布在 3 个国家目标入组 28 人开始时间: 2026年4月4日最近更新:
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 28
- 试验地点
- 7
- 主要终点
- Phase Ib: RP2D for epcoritamab based on incidence of DLTs
研究概览
简要总结
Phase Ib: To establish the recommended phase II dose (RP2D) for epcoritamab in patients with R/R WM, Phase II: To evaluate the preliminary efficacy of epcoritamab after 12 cycles in R/R WM patients in terms of major response rate (defined as complete remisson (CR), very good partial response (VGPR) or partial
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
- •Diagnosed with WM, according to criteria in appendix A
- •Negative serological testing for hepatitis B virus (HBV) (Hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) negative) and hepatitis C virus (hepatitis C antibody). Patients who are positive for anti-HBc or hepatitis C antibody may be included if they have a negative PCR within 6 weeks before enrollment. Those who are PCR positive will be excluded.
- •Negative pregnancy test at study entry for women of childbearing potential
- •Agreement to use adequate contraception during the trial and for 4 months after last epcoritamab administration, for women of childbearing potential or men sexually active with a woman of childbearing potential
- •Patient is capable of giving informed consent
- •Written informed consent
- •Age ≥ 18 years
- •Indication for therapy based on IWMM consensus criteria (see appendix A)
- •Relapsed or refractory WM
- •At least 1 prior line of systemic therapy for WM (including at least: either a BTK-inhibitor or an anti-CD20 antibody combined with chemotherapy)
- •Measurable disease (IgM M-protein > 5 g/L or, in case M-protein is present but unquantifiable, total serum IgM level > 10 g/L)
- •BM LPL infiltrate positive for CD20 at screening
- •Acceptable Complete Blood Count (CBC), renal function, liver function and coagulation status, defined as per the following laboratory measurements: o Hemoglobin (Hb) > 5.6 mmol/L or Hb > 9 g/dL (unless related to WM) o Estimated creatinin clearance > 45 mL/min (Cockroft-Gault) o Serum ALT ≤ 3.0 upper limit of normal (ULN) o Serum AST ≤ 3.0 ULN o Total billirubin ≤ 1.5 x ULN (unless attributable to Gilbert’s syndrome or controlled autoimmune hemolytic anemia) o Absolute neutrophil count (ANC) > 1.0 x 109/L, unless neutropenia is due to BM involvement of WM in which case the minimum is > 0.5 x 109/L o Platelet count > 30 x109/L unless trombopenia is due to BM involvement of WM in which case the minimum is > 10 x 109/L o Prothrombin Time (PT), International Normalized Ratio (INR), and Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN (unless receiving anticoagulation)
- •ECOG/WHO performance status ≤ 2 (see appendix D)
排除标准
- •Large cell transformation, central nervous system (CNS) involvement/Bing Neel Syndrome and/or AL (Amyloid Light-Chain) Amyloidosis
- •Has suspected active or inadequately treated latent tuberculosis
- •Severe cardiovascular disease (New York Heart Association (NYHA) classification III-IV; see appendix G) (arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease)
- •Severe pulmonary dysfunction (CTCAE grade III-IV, see appendix F)
- •Severe neurological dysfunction including psychiatric disease CTCAE grade III-IV (see appendix F)
- •Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, cancer, etc.)
- •History of active malignancy (other than inclusion diagnosis) with the exception of: o Non-invasive basal cell or squamous cell skin carcinoma o Cervical carcinoma, stage 1B or less o Non-invasive, superficial bladder cancer o Prostate cancer with a current PSA level < 0.1 ng/mL o Any curable cancer with a CR of > 2 years duration
- •Uncontrolled HIV infection. Patients with HIV positivity but with viral suppression (VL< lower limit of detection) and CD4 count > 350 for over 1 year, no history of AIDS-defining illnesses with the exception of lymphoma diagnosis may be enrolled.
- •Patients with an active HBV and/or HCV infection.
- •Patients with symptomatic IgG or IgA or non-secreting LPL
- •Uncontrolled hyperviscosity syndrome and/or Plasmapheresis < 35 days prior to screening and/or initiation of study drug
- •Peripheral neuropathy of CTCAE grade ≥ 3
- •Vaccination with live attenuated vaccines within 28 days prior to registration
- •Major surgery within 28 days prior to registration
- •Breastfeeding or pregnant female patients
- •Current participation in another clinical trial with medicinal products
- •Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- •Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient
- •Recent WM treatment: o For chemotherapy and/or rituximab and/or bortezomib and/or other proteasome inhibitors: within 4 weeks prior to first epcoritamab dose. o For BTK-inhibitors (monotherapy): within 14 days, prior to the first dose of epcoritamab o For autoSCT (autologous stem cell transplantation): 100 days prior to first epcoritimab dose. o For any other treatment and/or investigational drug: 4 weeks or 5 half-lives prior to first epcoritamab dose, whichever is longer, prior to the planned first dose of epcoritamab
- •Prior solid organ or allogeneic hematopoietic stem cell transplantation (prior autoSCT is acceptable)
- •Prior treatment with a CD3 × CD20 bispecific antibody
- •Autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy, including indication for systemic cortisteroids at > 10 mg daily prednisone or equivalent.
- •History of drug-specific hypersensitivity or anaphylaxis to any study drug (including active product or excipient components)
- •Active bleeding or uncontrolled severe bleeding diathesis (e.g., hemophilia or severe von Willebrand disease)
- •Ongoing active bacterial, viral, fungal, mycobacterial, parasitic or other infection requiring systemic treatment (excluding prophylactic treatment) at the time of enrollment or within the previous 2 weeks prior to the planned first dose of trial drug, including COVID-19 infection. Note that a past COVID-19 infection may be a risk factor, but if resolved and the subject is vaccinated, it may be allowable to enroll the subject
研究组 & 干预措施
Epcoritamab (GEN3013), Epcoritamab (GEN3013)
Test
干预措施: Epcoritamab (GEN3013) (Drug)
结局指标
主要结局
Phase Ib: RP2D for epcoritamab based on incidence of DLTs
Phase Ib: RP2D for epcoritamab based on incidence of DLTs
Phase II: Major response rate (defined as CR, VGPR or PR) after 12 cycles of epcoritamab
Phase II: Major response rate (defined as CR, VGPR or PR) after 12 cycles of epcoritamab
次要结局
- Phase II: Duration of response (DOR), defined as time from first response to progressive disease (PD) or death from any cause
- Phase II: Time to response, time to best response and best response on protocol
- Phase II: Categorical response rates (PD, SD, MR, PR, VGPR, CR) after 12 and after 24 cycles of epcoritamab
- Phase II: Progression-free survival (PFS), defined as time from start epcoritamab to the first occurrence of disease progression or death from any cause, whichever occurs first
- Phase II: Time on treatment (TOT), defined as time from first epcoritamab dose to last administration of epcoritamab
- Phase II: Overall survival (OS), defined as the time from start epcoritamab to death from any cause
- Phase II: Time to next treatment (TTNT), defined as time from start epcoritamab to next line of WM treatment.
- Phase II: Treatment free survival (TFS), defined as time from date of last protocol treatment to date start of next (new) line of treatment, or death from any cause, whichever comes first
- Phase II: Safety parameters: Type, frequency, and severity of- adverse events (AEs) and- AEs of special interest (AESI) and their relationship to study treatment (determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0)
- Phase II: Health-related quality of life (QoL) by EORTC QLQ-C30
研究者
Dr. J.M.I. Vos
Scientific
Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting
研究点 (7)
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