NCT05370430招募中1 期
A Phase 1 Study Evaluating BAFFR-targeting CAR T Cells for Patients With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma (B-NHL)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 36
- 试验地点
- 6
- 主要终点
- Incidence of adverse events
研究概览
简要总结
A Phase 1 Study Evaluating BAFFR-targeting CAR T Cells for Patients with Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma (B-NHL)
详细描述
This phase I trial evaluates the side effects and best dose of BAFFR-CAR T cells in treating patients with B-cell Non-Hodgkin's Lymphoma (B-NHL) that has come back (recurrent) or does not respond to treatment (refractory). T cells are infection fighting blood cells that can kill cancer cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize BAFFR, a protein on the surface of cancer cells. These BAFFR-specific T cells may help the body's immune system identify and kill BAFFR+ cancer cells.
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
- •Informed Consent: Signed informed consent by the participant or legally authorized representative.
- •Age & Performance Status:
- •Age ≥ 18 years
- •ECOG performance status ≤ 2
- •Diagnosis & Disease Criteria:
- •Histologically confirmed B-NHL, including LBCL, MCL, and FL/MZL subtypes meeting specified prior treatment conditions.
- •BAFF-R expression on lymphoma cells required.
- •Measurable Disease: Tumor ≥1.5 cm on CT/PET scan or evidence of disease in blood, BM, GI, skin, or spleen.
- •Prior CAR T-cell Therapy: Allowed if ≥ 3 months since last treatment and CD19 CAR-T persistence < 5% before leukapheresis.
- •Organ Function & Laboratory Criteria:
- •Hematologic: ANC ≥ 1000/μL, Platelets ≥ 75,000/μL (exceptions for BM involvement).
- •Liver Function: Bilirubin ≤ 1.5x ULN (except Gilbert's), AST/ALT < 3x ULN.
- •Renal Function: CrCl ≥ 50 mL/min.
- •Cardiac & Pulmonary: LVEF ≥ 45%, QTcF ≤ 480 ms, O₂ saturation > 91% on room air.
- •Infectious Disease Screening: Seronegative for HIV, active HBV, active HCV (or undetectable viral load if positive).
- •Reproductive Considerations:
- •Negative pregnancy test for females of childbearing potential.
- •Use of effective contraception or abstinence through 3 months post-treatment.
排除标准
- •Prior Therapies & Transplants:
- •Prior allogeneic SCT.
- •Autologous SCT < 6 months before leukapheresis.
- •Concurrent systemic steroids or chronic immunosuppressant use.
- •Disease-Specific Exclusions:
- •Cardiac lymphoma involvement.
- •Need for urgent therapy due to tumor-related complications (e.g., bowel obstruction).
- •Medical Conditions:
- •Active autoimmune disease requiring immunosuppressants.
- •Primary immunodeficiency.
- •Cardiac conditions, including NYHA Class III/IV heart disease, arrhythmia, recent MI (≤ 6 months), stroke (≤ 6 months), or significant VTE (≤ 6 months).
- •Neurologic conditions, including prior optic neuritis, CNS inflammatory diseases, or seizure disorders.
- •History of malignancy, unless resected/treated with curative intent or in remission for ≥ 3 years.
- •Uncontrolled systemic infections or active CNS lymphoma.
- •Pregnancy & Breastfeeding: Females who are pregnant or nursing.
- •Other Considerations:
- •Investigator-determined safety concerns.
- •Potential noncompliance with study procedures.
研究组 & 干预措施
B-cell activating factor receptor-Chimeric antigen receptor T cells [BAFFR-CAR T cells]
Experimental
BAFFR-CAR T cells in participants with r/r B-NHL
干预措施: BAFFR-CAR T cells (Biological)
结局指标
主要结局
Incidence of adverse events
时间窗: Up to 1 year post treatment
Assess the safety of administering BAFFR-CAR T cells in participants with relapsed or refractory (r/r) B-cell Non-Hodgkin's Lymphoma (B-NHL) and it's subtypes. Toxicity will be graded per Common Terminology Criteria for Adverse Events version 5.0, Cytokine Release Syndrome (CRS) and neurotoxicity which use the American Society for Transplantation and Cellular Therapy Consensus Criteria (ASTCT) and Graft versus Host Disease (GVHD) criteria. Toxicities will be followed from the start of lymphodepletion until the end of the study.
Maximum Tolerated Dose (MTD)
时间窗: The DLT evaluation period is defined as 28 days following BAFFR CAR-T infusion.
Determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) of BAFFR-CAR T cells. The highest dose with ≤ 1/6 participants with DLT will be considered the MTD.
次要结局
- Disease Response(Up to 1 year post treatment)
- Minimal Residual Disease (MRD)(Up to 1 year post treatment)
- B Cell Quantification(Up to 1 year post treatment)
- Overall Survival (OS)(From the day of BAFFR-CAR T cell infusion to death from any cause assessed, up to 15 years.)
- Progression-free survival (PFS)(From CAR T cell infusion to the first observation of disease relapse/progression or death from any cause, whichever occurs first, assessed up to 15 years.)
研究者
研究点 (6)
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相关资讯
Lancet Publishes Phase 1 Data for PeproMene's BAFF-R CAR T: 80% Complete Response, Grade 1-Only Toxicity- PeproMene Bio's BAFF-R-targeted CAR T-cell therapy PMB-CT01 achieved complete responses in seven of nine heavily pretreated relapsed or refractory B-cell non-Hodgkin lymphoma patients in Phase 1.
- Four of six patients who had progressed after prior CD19-directed CAR T-cell therapy responded, with all complete responses ongoing at data cutoff and the longest exceeding 35 months.
- All cytokine release syndrome events and the two reported ICANS events were Grade 1 only, a profile the company says may support future outpatient administration.
- The Institute for Follicular Lymphoma Innovation committed up to USD 11 million in December 2024 to support PMB-CT01 development in relapsed or refractory follicular lymphoma.7 days agoPeproMene Bio's BAFF-R CAR-T Therapy Shows 78% Complete Response Rate in B-Cell Lymphoma Patients After CD19 CAR-T Failure- PeproMene Bio's PMB-CT01, a first-in-class BAFF-R-targeted CAR-T therapy, achieved a 78% complete response rate in nine patients with relapsed/refractory B-cell non-Hodgkin lymphoma.
- The therapy demonstrated a favorable safety profile with no dose-limiting toxicities, no grade >1 cytokine release syndrome, and no grade >1 immune effector cell-associated neurotoxicity syndrome.
- All seven responding patients achieved minimal residual disease-negative status with durable responses, including the longest response exceeding three years without any relapses.
- The treatment showed efficacy in patients whose cancer progressed following standard CD19-directed CAR-T therapy, addressing a significant unmet medical need.3 months agoPeproMene Bio's BAFFR-CAR T Therapy Shows Promising Results in Relapsed B-Cell Cancers- PeproMene Bio's PMB-CT01, a first-in-class BAFFR-CAR T therapy, achieved complete responses in all seven B-NHL patients and four of six B-ALL patients in Phase 1 trials.
- The therapy demonstrated exceptional safety with no Grade ≥1 cytokine release syndrome or neurotoxicity in B-NHL patients and minimal toxicity in B-ALL patients.
- PMB-CT01 showed efficacy in CD19-negative patients and those who failed prior CD19-directed therapy, with remissions lasting up to 32+ months.
- Two abstracts from the ongoing Phase 1 studies have been selected for oral presentations at the 2025 ASH Annual Meeting.10 months agoNovel BAFF-R CAR-T Therapy Achieves Complete Response in Heavily Pretreated Follicular Lymphoma Patient- PeproMene Bio's first-in-class BAFF-R targeted CAR-T cell therapy (PMB-CT01) has achieved complete remission in a heavily pretreated follicular lymphoma patient who had failed seven prior therapies including CD19 CAR-T.
- All seven patients with relapsed/refractory B-cell non-Hodgkin lymphoma treated with PMB-CT01 have achieved complete responses lasting from 1 to 29+ months, with minimal toxicity reported.
- PMB-CT01 targets the BAFF receptor, which is crucial for B-cell survival, potentially making it harder for tumor cells to escape therapy through antigen loss compared to CD19-targeted approaches.last yearPeproMene Bio's BAFFR-CAR T Cell Therapy Shows Promise in Relapsed B-ALL Trial- PeproMene Bio reports complete remission in the first patient treated with PMB-CT01 (BAFFR-CAR T cells) for relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).
- The Phase 1 trial at City of Hope showed minimal toxicity, with only low-grade cytokine release syndrome that resolved without intervention.
- The patient, with CD19- and CD22-negative relapsed B-ALL, had limited therapeutic options prior to receiving PMB-CT01.
- PMB-CT01, a first-in-class BAFFR-targeted CAR T-cell therapy, demonstrates potential in overcoming B-cell malignancies, supported by preclinical data.2 years ago