A Phase I Study Evaluating Escalating Doses of 90Y-BC8-DOTA (Anti-CD45) Antibody Followed by Autologous Stem Cell Transplantation for Relapsed or Refractory Lymphoid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 2
- 主要终点
- Percentage of Participants With Dose Limiting Toxicities (DLT) of Yttrium-90 Anti-CD45
研究概览
简要总结
This phase I trial studies the side effects and best dose of monoclonal antibody therapy before stem cell transplant in treating patients with relapsed or refractory lymphoid malignancies. Radiolabeled monoclonal antibodies, such as yttrium-90 anti-CD45 monoclonal antibody BC8, can find cancer cells and carry cancer-killing substances to them without harming normal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Giving radiolabeled monoclonal antibody before a stem cell transplant may be an effective treatment for relapsed or refractory lymphoid malignancies.
详细描述
PRIMARY OBJECTIVES:
I. To estimate the maximally tolerated dose (MTD) of 90Y-BC8-DOTA (anti-cluster of differentiation [CD]45) (yttrium-90 anti-CD45 monoclonal antibody BC8) that can be delivered prior to autologous stem cell transplantation for patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL), T-cell NHL (T-NHL), and Hodgkin lymphoma (HL).
SECONDARY OBJECTIVES:
I. To optimize the protein dose (antibody [Ab]) to deliver a favorable biodistribution in the majority of patients.
II. To describe the impact of rituximab concentrations, B-cell depletion, and disease burden on CD20 and CD45 targeting.
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
- •Patients must have a histologically confirmed diagnosis of B-NHL, T-NHL, or HL; only patients with classical HL must have documented histologic demonstration of CD45+ cells adjacent to the Reed Sternberg cells; patients must have received at least one prior standard systemic therapy with documented recurrent or refractory disease; patients with mantle cell lymphoma (MCL), T-NHL, or other high-risk malignancies may be enrolled/transplanted in complete remission (CR)/first partial remission (PR1)
- •Creatinine < 2.0
- •Bilirubin < 1.5 mg/dL
- •All patients eligible for therapeutic study must have a minimum of >= 2 x 10^6 CD34/kg autologous hematopoietic stem cells harvested and cryopreserved
- •Patients must have an expected survival of > 60 days and must be free of major infection
- •Patients are preferred to have either a tumor mass amenable to core needle biopsy during the dosimetry phase, or a measurable tumor mass with at least one site of involvement measuring 2.5 cm in largest dimension on computed tomography (CT) imaging for purposes of planar and/or single-photon emission computed tomography (SPECT)/CT tumor dosimetry
排除标准
- •Circulating human anti-mouse antibody (HAMA), to be determined before each infusion
- •Systemic anti-lymphoma therapy given in the previous 30 days before the scheduled therapy dose with the exception of rituximab
- •Inability to understand or give an informed consent
- •Lymphoma involving the central nervous system
- •Other serious medical conditions considered to represent contraindications to ASCT (e.g., abnormally decreased cardiac ejection fraction, diffusion capacity of the lung for carbon monoxide [DLCO] < 50% predicted, acquired immune deficiency syndrome [AIDS], etc.)
- •Known human immunodeficiency virus (HIV) seropositivity
- •Pregnancy or breast feeding
- •Prior allogeneic bone marrow or stem cell transplant
- •Prior autologous bone marrow or stem cell transplant within 1 year of enrollment
- •Prior radiation therapy (RT) > 20 Gray (Gy) to a critical organ within 1 year of enrollment
- •Southwest Oncology Group (SWOG) performance status >= 2.0
- •Patients with relapsed diffuse large B-cell lymphoma (DLBCL) or HL that have achieved a positron emission tomography (PET)-negative CR following first salvage chemotherapy
结局指标
主要结局
Percentage of Participants With Dose Limiting Toxicities (DLT) of Yttrium-90 Anti-CD45
时间窗: Up to 30 days after receiving study drug
A DLT (dose limiting toxicity) is defined as a therapy-related grade III or IV Bearman (transplant) toxicity within 30 days of transplant.
次要结局
- Tumor to Normal Organ Ratios(Up to 6 years)
- Overall Response Rate(Up to 6 years)
- Overall Survival(Up to 6 years)
- Progression-free Survival(Up to 6 years)
研究者
Ajay Gopal
Principal Investigator
Fred Hutchinson Cancer Center