Evaluation of Pretargeted Anti-CD20 Radioimmunotherapy Combined With BEAM Chemotherapy and Autologous Stem Cell Transplantation for High-Risk B-Cell Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Yttrium Y 90 DOTA-biotin Defined as the Dose That is Associated With a True Dose Limiting Toxicity (DLT) Rate of 25%, Where a DLT is Defined as a Therapy-related Grade III or IV Bearman (Transplant) Toxicity
研究概览
简要总结
This phase I/II trial studies the side effects and best dose of anti-cluster of differentiation (CD)20 radioimmunotherapy (RIT), and to see how well it works when given before chemotherapy and stem cell transplant in treating patients with B-cell malignancies that have not responded to treatment or have come back after responding to treatment. CD20 is a protein found on the cells of a type of cancer cell called B-cells. Anti-CD20 RIT attaches radioactive material to a drug that is designed to target CD20, which brings radioactive material to the cancer cells to kill the cells. This may kill more tumor cells while causing fewer side effects to healthy tissue. Adding anti-CD20 to standard chemotherapy and stem cell transplant may be more effective in treating patients with B-cell malignancies.
详细描述
PRIMARY OBJECTIVES:
I. To estimate the maximum tolerated dose (MTD) of 90Y activity that can be delivered via pretargeted radioimmunotherapy (PRIT) using B9E9-fusion protein (B9E9-FP), clearing agent (CA), and radiolabeled tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin when followed by carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy and autologous stem cell transplantation.
SECONDARY OBJECTIVES:
I. To assess the overall and progression-free survival of the above regimen in such patients.
II. To evaluate the response rates of the above therapy.
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 lymphoma expressing the CD20 antigen and generally must have failed at least one prior standard systemic therapy; the exception will be mantle cell lymphoma (MCL) patients, who may be enrolled while in first complete remission (CR) as well as other select high-risk lymphomas (e.g., Burkitt?s, double hit diffuse large B-cell lymphoma [DLBCL], transformed indolent B-cell non-Hodgkin lymphoma [B-NHL], etc.) in accordance with current transplant standard of care for these patients
- •Creatinine (Cr) < 2.0
- •Bilirubin < 1.5 mg/dL, with the exception of patients thought to have Gilbert?s syndrome, who may have a total bilirubin above 1.5 mg/dL
- •All patients eligible for therapeutic study must have (>= 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 of childbearing potential must agree to abstinence or the use of effective contraception
- •DONOR SELECTION: Not applicable; this protocol employs autologous transplantation, utilizing the patient?s own hematopoietic stem cells obtained from either the peripheral blood or bone marrow
排除标准
- •Systemic anti-lymphoma therapy given in the previous 30 days before the scheduled 90Y therapy dose
- •Inability to understand or give an informed consent
- •Prior radiation > 20 Gy to any critical normal organ (e.g., lung, liver, spinal cord, both kidneys) within 1 year of the treatment date
- •Active central nervous system lymphoma
- •Other serious medical conditions considered to represent contraindications to bone marrow transplant (BMT) (e.g., abnormally decreased cardiac ejection fraction, diffusion capacity of the lung for carbon monoxide [DLCO] < 50% predicted, patient on supplemental oxygen, acquired immune deficiency syndrome [AIDS], etc.)
- •Pregnancy or breast feeding
- •Prior bone marrow or stem cell transplant
- •Southwest Oncology Group (SWOG) performance status >= 2.0
- •Known sensitivity to kanamycin and other aminoglycosides; patients with known hypersensitivity to kanamycin or any other aminoglycoside antibiotic will be excluded
研究组 & 干预措施
Treatment (PRIT)
B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17.
CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15.
RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14.
BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2.
STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care.
干预措施: Anti-CD20 B9E9 scFv-Streptavidin Fusion Protein (Biological)
Treatment (PRIT)
B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17.
CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15.
RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14.
BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2.
STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care.
干预措施: Autologous Hematopoietic Stem Cell Transplantation (Procedure)
Treatment (PRIT)
B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17.
CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15.
RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14.
BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2.
STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care.
干预措施: Carmustine (Drug)
Treatment (PRIT)
B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17.
CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15.
RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14.
BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2.
STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care.
干预措施: Clearing Agent (Drug)
Treatment (PRIT)
B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17.
CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15.
RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14.
BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2.
STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care.
干预措施: Cytarabine (Drug)
Treatment (PRIT)
B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17.
CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15.
RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14.
BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2.
STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care.
干预措施: Etoposide (Drug)
Treatment (PRIT)
B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17.
CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15.
RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14.
BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2.
STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care.
干预措施: Indium In 111-DOTA-Biotin (Radiation)
Treatment (PRIT)
B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17.
CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15.
RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14.
BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2.
STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (PRIT)
B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17.
CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15.
RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14.
BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2.
STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care.
干预措施: Melphalan (Drug)
Treatment (PRIT)
B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17.
CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15.
RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14.
BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2.
STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care.
干预措施: Peripheral Blood Stem Cell Transplantation (Procedure)
Treatment (PRIT)
B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17.
CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15.
RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14.
BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2.
STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care.
干预措施: Pharmacological Study (Other)
Treatment (PRIT)
B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17.
CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15.
RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14.
BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2.
STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care.
干预措施: Yttrium Y 90-DOTA-Biotin (Radiation)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Yttrium Y 90 DOTA-biotin Defined as the Dose That is Associated With a True Dose Limiting Toxicity (DLT) Rate of 25%, Where a DLT is Defined as a Therapy-related Grade III or IV Bearman (Transplant) Toxicity
时间窗: Up to 30 days after transplant
Following the completed observation of the final patient, a two-parameter logistic model will be fit to the data, thereby generating a dose-toxicity curve based on the observed DLT rate at the various dose levels visited. Based on this fitted model, the MTD is estimated to be the dose that is associated with a DLT rate of 25%.
次要结局
- Incidence of Toxicity, Defined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0(Up to 30 days after transplant)
- Dosimetry of Yttrium Y 90 DOTA-biotin(Up to 7 days after infusion)
- Overall Survival(Up to 4 years)
- Progression Free Survival (PFS)(1 year from autologous stem cell transplant)
- Overall Response Rate(Up to 4 years)