NCT01685008已完成2 期
A Phase IIa, Open-label, Multicenter Study of Single-agent MOR00208, an Fc-optimized Anti-CD19 Antibody, in Patients With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- MorphoSys AG
- 入组人数
- 92
- 试验地点
- 3
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
This is an open-label, multicenter study to characterize the safety and efficacy of the human anti-CD19 antibody MOR00208 in adult patients with relapsed/refractory non-Hodgkin's lymphoma (NHL) who have received at least 1 prior therapy containing rituximab (at least once).
详细描述
The study enrols patients from four different NHL subtypes: follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL) and other indolent NHL (iNHL). The study will employ a two-stage design where the decision to further enrol any NHL subtype in stage 2 will depend on best responses after two or three cycles in stage 1.
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
- •Male or female patients ≥ 18 years of age.
- •Histologically-confirmed diagnosis according to Revised European American Lymphoma/World Health Organization classification, of the following B-cell lymphomas:
- •Other indolent NHL (eg, MZL/MALT)
- •Patients' NHL must have progressed after at least 1 prior rituximab containing regimen.
- •One site of measurable disease by magnetic resonance imaging (MRI) or computed tomography (CT) scan defined as at least one lesion that measures at least 1.5 × 1.5 cm.
- •For patients with MCL only, patients with nonmeasurable disease but evaluable sites (bone marrow, spleen, peripheral blood, gastrointestinal tract) can be enrolled.
- •Patients who have previously received an autologous stem cell transplantation must be at least 4 weeks post-transplant before study drug administration and must have exhibited a full haematological recovery.
- •Discontinued previous monoclonal antibody therapy (except rituximab) or radioimmunotherapy administration for at least 60 days before study drug administration.
- •Off rituximab for at least 14 days before the screening visit and be confirmed to have either no response or have disease progression after rituximab treatment.
- •Patients with DLBCL had a positive [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) scan at baseline (Cheson 2007 response criteria).
- •Life expectancy of > 3 months.
- •Eastern Cooperative Oncology Group (ECOG) performance status of <
- •Laboratory criteria at screening:
- •Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L
- •Platelet count ≥ 75 × 10^9/L without previous transfusion within 10 days of first study drug administration
- •Haemoglobin ≥ 8.0 g/dL (may have been transfused)
- •Serum creatinine < 2.0 x upper limit of normal (ULN)
- •Total bilirubin ≤ 2.0 × ULN
- •Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN
- •If a female of childbearing potential, a negative pregnancy test must be confirmed before enrolment and use of double-barrier contraception or oral contraceptive plus barrier contraceptive must be used during the study and for 3 months after the last dose, or confirmation of having undergone clinically documented total hysterectomy and/or oophorectomy, tubal ligation.
- •If a male, an effective barrier method of contraception must be used during the study and for 3 months after the last dose if the patient is sexually active with a female of childbearing potential.
- •Able to comply with all study-related procedures, medication use, and evaluations.
- •Able to understand and give written informed consent and comply with the study protocol.
排除标准
- •Previous treatment with cytotoxic chemotherapy, immunotherapy, radiotherapy or other lymphoma specific therapy within 14 days before the screening visit or patient has not recovered from side effects of previous lymphoma-specific therapy.
- •Treatment with a systemic investigational agent within 28 days before the screening visit.
- •Previous treatment with an anti-CD19 antibody or fragments.
- •Previous allogenic stem cell transplantation.
- •Known or suspected hypersensitivity to the excipients contained in the study drug formulation.
- •Clinically significant cardiovascular disease or cardiac insufficiency, cardiomyopathy, preexisting clinically significant arrhythmia, acute myocardial infarction within 3 months of enrolment, angina pectoris within 3 months of enrolment.
- •Patients with positive hepatitis serology:
- •Hepatitis B (HBV): Patients with positive serology for HBV defined as positivity for hepatitis B surface antigen (HBsAg) or total anti-hepatitis B core antibody (anti-HBc). Patients positive for anti-HBc may be included if HBV DNA is not detectable.
- •Hepatitis C (HCV): Patients positive HCV serology (defined as positive for anti-HCV antibody [anti-HCV]) unless HCV-ribonucleic acid (RNA) is confirmed negative.
- •History of HIV infection.
- •Any active systemic infection (viral, fungal, or bacterial) requiring active parenteral antibiotic therapy within 4 weeks of study drug administration.
- •Current treatment with immunosuppressive agents other than prescribed corticosteroids (not more than 10-mg prednisone equivalent).
- •Major surgery or radiation therapy within 4 weeks before first study drug administration.
- •Systemic diseases (cardiovascular, renal, hepatic, etc) that would prevent study treatment in the investigator's opinion.
- •History or clinical evidence of central nervous system (CNS), meningeal, or epidural disease, including brain metastasis.
- •Active treatment/chemotherapy for another primary malignancy within the past 5 years (except for ductal breast cancer in situ, non-melanoma skin cancer, prostate cancer not requiring treatment, and cervical carcinoma in situ).
- •Pregnancy or breastfeeding in women and women of childbearing potential not using an acceptable method of birth control.
- •History of noncompliance to medical regimens or patients who are considered potentially unreliable not cooperative.
研究组 & 干预措施
MOR00208 (formerly Xmab5574)
Experimental
intravenous Infusion of MOR00208, Fc-Optimized Anti-CD19 Antibody
干预措施: MOR00208 (formerly Xmab 5574) (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: From first dose until Follow-up Visit 12, up to 4.5 years
Proportion of patients with Complete Remission (CR; disappearance of all evidence of disease) or Partial Remission (PR; regression of measurable disease and no new sites), assessed as per the 2007 International Working Group (IWG) response criteria by radiographic evaluations (CT, PET, MRI, or other).
次要结局
- Progression-free Survival (PFS)(From first dose until Follow-up Visit 12, up to 4.5 years)
- Duration of Response (DoR)(From first dose until Follow-up Visit 12, up to 4.5 years)
- Number and Proportion of Patients Who Potentially Developed Anti-MOR00208 Antibodies and Semiquantitative Anti-MOR00208 Antibody Assessments(From first dose until Follow-up Visit 3, up to 7 months)
- Pharmacokinetic (PK) Parameter: Maximum Serum Concentration Observed (Cmax) of MOR00208(Estimated from first dose (samples taken on first day of dosing at pre-dose, end of infusion, after 1 hour, 4 hours, 24 hours, and pre-dose on Day 8))
- Incidence and Severity of Adverse Events (AEs)(From first dose until 30 days after last dose of MOR00208, up to 8.5 years)
- Time to Progression (TTP)(From first dose until Follow-up Visit 12, up to 4.5 years)
- PK Parameter: Apparent Terminal Half-life (t[1/2]) of MOR00208(Estimated from final dose (samples collected on the last day of Cycle 3 [C3D28; each cycle is 28 days long], and Follow-up Visits 1 [C3D28 + 4 weeks], 2 [C3D28 + 10 weeks], and 3 [C3D28 + 16 weeks]))
- Percent Change From Baseline in Measurements of B-cell Populations(Cycle 1 Day 1 (Baseline) to Cycle 1: Days 8, 15, and 22; Cycles 2 and 3: Days 1, 15, and 28 (each cycle is 28 days); End of Study (up to 7.5 years))
- Stable Disease (SD) Rate(From first dose until Follow-up Visit 12, up to 4.5 years)
- PK Parameter: Apparent Terminal Rate Constant (λz) of MOR00208(Estimated from final dose (samples collected on the last day of Cycle 3 [C3D28; each cycle is 28 days long], and Follow-up Visits 1 [C3D28 + 4 weeks], 2 [C3D28 + 10 weeks], and 3 [C3D28 + 16 weeks]))
- Absolute Change From Baseline in Measurements of T-cell Populations(Cycle 1 Day 1 (Baseline) to Cycle 1: Days 8, 15, and 22; Cycles 2 and 3: Days 1, 15, and 28 (each cycle is 28 days); End of Study (up to 7.5 years))
- Evaluation of AEs Stratified by FcγRIIIa Polymorphism(From first dose until 30 days after last dose of MOR00208, up to 8.5 years)
- Evaluation of ORR Stratified by FcγRIIa Polymorphism(From first dose until Follow-up Visit 12, up to 4.5 years)
- PK Parameter: Time to Maximum Serum Concentration Observed (Tmax) of MOR00208(Estimated from first dose (samples taken on first day of dosing at pre-dose, end of infusion, after 1 hour, 4 hours, 24 hours, and pre-dose on Day 8))
- PK Parameter: Apparent Trough Serum Concentration Before Dosing (Clast) of MOR00208(Estimated from first dose (samples taken on first day of dosing at pre-dose, end of infusion, after 1 hour, 4 hours, 24 hours, and pre-dose on Day 8))
- PK Parameter: Area Under the Concentration Curve From Dose Time Zero to Infinity (AUC[0-inf]) of MOR00208(Estimated from final dose (samples collected on the last day of Cycle 3 [C3D28; each cycle is 28 days long], and Follow-up Visits 1 [C3D28 + 4 weeks], 2 [C3D28 + 10 weeks], and 3 [C3D28 + 16 weeks]))
- PK Parameter: Total Body Clearance (CL) of MOR00208(Estimated from final dose (samples collected on the last day of Cycle 3 [C3D28; each cycle is 28 days long], and Follow-up Visits 1 [C3D28 + 4 weeks], 2 [C3D28 + 10 weeks], and 3 [C3D28 + 16 weeks]))
- Percent Change From Baseline in Measurements of NK Cell Populations(Cycle 1 Day 1 (Baseline) to Cycle 1: Days 8, 15, and 22; Cycles 2 and 3: Days 1, 15, and 28 (each cycle is 28 days); End of Study (up to 7.5 years))
- PK Parameter: Area Under the Concentration Curve From Dose Time Zero to the Time the Last Quantifiable Concentration is Observed (AUC[0-t]) of MOR00208(Estimated from first dose (samples taken on first day of dosing at pre-dose, end of infusion, after 1 hour, 4 hours, 24 hours, and pre-dose on Day 8))
- Absolute Change From Baseline in Measurements of B-cell Populations(Cycle 1 Day 1 (Baseline) to Cycle 1: Days 8, 15, and 22; Cycles 2 and 3: Days 1, 15, and 28 (each cycle is 28 days); End of Study (up to 7.5 years))
- Absolute Change From Baseline in Measurements of NK Cell Populations(Cycle 1 Day 1 (Baseline) to Cycle 1: Days 8, 15, and 22; Cycles 2 and 3: Days 1, 15, and 28 (each cycle is 28 days); End of Study (up to 7.5 years))
- Evaluation of ORR Stratified by Baseline CD19 Expression on Malignant Lymphoma Cells(From first dose until Follow-up Visit 12, up to 4.5 years)
- Evaluation of AEs Stratified by FcγRIIa Polymorphism(From first dose until 30 days after last dose of MOR00208, up to 8.5 years)
- PK Parameter: Apparent Volume of Distribution (Vz) of MOR00208(Estimated from final dose (samples collected on the last day of Cycle 3 [C3D28; each cycle is 28 days long], and Follow-up Visits 1 [C3D28 + 4 weeks], 2 [C3D28 + 10 weeks], and 3 [C3D28 + 16 weeks]))
- Percent Change From Baseline in Measurements of T-cell Populations(Cycle 1 Day 1 (Baseline) to Cycle 1: Days 8, 15, and 22; Cycles 2 and 3: Days 1, 15, and 28 (each cycle is 28 days); End of Study (up to 7.5 years))
- Evaluation of AEs Stratified by Baseline CD19 Expression on Malignant Lymphoma Cells(From first dose until 30 days after last dose of MOR00208, up to 8.5 years)
- Evaluation of ORR Stratified by FcγRIIIa Polymorphism(From first dose until Follow-up Visit 12, up to 4.5 years)
研究者
研究点 (3)
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