NCT04690595进行中（未招募）1 期
A Phase 1 Study Evaluating BAFFR-targeting CAR T Cells for Patients With Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 24
- 试验地点
- 1
- 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 Acute Lymphoblastic Leukemia
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 Acute Lymphoblastic Leukemia 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
- •Documented informed consent of the participant and/or legally authorized representative.
- •Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If unavailable, exceptions may be granted with study PI approval.
- •Age ≥ 18 years.
- •Life expectancy ≥ 16 weeks.
- •Histologically confirmed B-ALL or B-cell lymphoblastic lymphoma
- •Relapsed/refractory disease after failure of ≥ 2 prior lines of therapy.
- •Evidence of active BAFF-R expression at the time of enrollment.
- •Recovered to ≤ Grade 1 from the acute toxic effects (except alopecia) of prior anti-cancer therapy.
- •No known contraindications to leukapheresis, steroids or tocilizumab.
- •Ineligible for or failed prior CD19-targeted immunotherapy (e.g., blinatumomab or CD19-CAR T cells).
- •For participants who had prior CD19-CAR T cell therapy:
- •- At least 90-days has elapsed since participant received last CD19-CAR T cell therapy.
- •- Persistence of prior CD19-CAR T cells must be evaluated and found to be <5% prior to leukapheresis procedure
- •Participants with CNS involvement by leukemia (CNS2 and asymptomatic CNS3) may be considered eligible after discussions with the study team.
- •Total serum bilirubin ≤ULN (unless has Gilbert's disease, then ≤3.0)
- •Creatinine clearance of ≥ 40 mL/min per 24-hour urine test or the Cockcroft-Gault formula
- •Left ventricular ejection fraction (LVEF) ≥ 50%
- •O2 saturation ≥ 92% on room air.
- •Seronegative for HIV Ag/Ab combo, HCV*, and active HBV (Surface Antigen Negative)
- •*If positive, Hepatitis C RNA quantitation must be performed and must be undetectable.
- •Women of childbearing potential (WOCBP): negative urine or serum pregnancy test If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- •QuantiFERON-TB Gold or equivalent*
- •*Results do not impact patient eligibility, however the test must be initiated prior to enrollment
- •Agreement by females and males of childbearing potential^ to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy.
- •^Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only).
- •A complete liver evaluation (which includes ultrasound elastography, MRI of the liver and a hepatology consult) may be done if needed based on PI's recommendation.
- •Evaluation of acquired hemochromatosis (indicated through MRI of the liver and elevated levels of Ferritin) is recommended for participants who have undergone multiple transfusions and prior alloHCT.
排除标准
- •Autologous/allogeneic stem cell transplant within 100 days at the time of enrollment.
- •Immunosuppressant medications within 1 months prior to protocol enrollment.
- •Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. Physiologic replacement of steroids (prednisone ≤ 7.5 mg /day or equivalent) is allowed
- •Auto-immune disease or active GVHD within 4 months prior to protocol enrollment requiring systemic immunosuppressant therapy.
- •Class III/IV cardiovascular disability according to the New York Heart Association (NYHA) Classification.
- •Subjects with clinically significant arrhythmia or arrhythmias not stable on medical management within 2 weeks of enrollment.
- •Any abnormal liver enzyme levels (as defined ≥ULN in ALT, AST, Bilirubin and Alkaline Phosphatase levels) at time of enrollment
- •. Subjects with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, including seizure disorder.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent.
- •Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia.
- •History of venous occlusive disease (VOD), or GvHD.
- •a. Subjects with a history of the following GvHD may still be included in the study: i. Resolved Grade 2 or less steroid-sensitive acute skin GvHD ii. Grade 1 gastro-intestinal (GI)-GvHD developed within 100 days post prior alloHCT.
- •iii. Limited chronic GvHD
- •History of stroke or intracranial hemorrhage within 6 months of enrollment.
- •History of other malignancies, except for malignancy surgically resected (or treated with other modalities) with curative intent, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; non-muscle invasive bladder cancer; malignancy treated with curative intent with no known active disease present for ≥ 3 years.
- •Clinically significant uncontrolled illness.
- •Active systemic uncontrolled infection requiring antibiotics.
- •Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection.
- •Females only: Pregnant or breastfeeding.
- •Any other condition that would, in the investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures.
- •Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).
研究组 & 干预措施
BAFFR-CAR T cells
Experimental
B-cell activating factor receptor-Chimeric antigen receptor T cells
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
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.
次要结局
- Minimal residual disease (MRD)(Up to 1 year post treatment)
- B cell frequency(Up to 1 year post treatment)
- Disease response(Up to 1 year post treatment)
- Progression-free survival (PFS)(From T cell infusion to the first observation of disease relapse/progression or death from any cause, whichever occurs first, assessed up to 15 years.)
- Overall survival (OS)(From the day of BAFFR-CAR T cell infusion to death from any cause assessed, up to 15 years.)
- Severity of graft-versus-host disease (GVHD) in recipients of prior allogeneic hematopoietic stem cell transplantation(Up to 1 year post treatment.)
研究者
研究点 (1)
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相关资讯
PeproMene 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.9 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