Phase I/II Trial of Yttrium-90-labeled Daclizumab (Anti-CD25) Radioimmunotherapy With High-dose BEAM Chemotherapy and Autologous Hematopoietic Stem Cell Rescue in Recurrent and Refractory Hodgkin's Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Number of Participants With Adverse Events
研究概览
简要总结
Background:
- Hodgkins lymphoma (HL) is a highly treatable cancer. However, if HL does not respond to chemotherapy or returns after chemotherapy, further treatments often are not successful.
- Some HL cells have a molecule called cluster of differentiation 25 (CD25) on the surface. Daclizumab is a drug that can detect CD25 on cells. In a treatment study for HL that did not respond to chemotherapy, daclizumab plus a radioactive atom called Yttrium 90 helped kill these HL cells. Researchers want to combine this 90Y daclizumab with high-dose chemotherapy and stem cell transplant. This treatment may be more effective than the daclizumab alone.
Objectives:
- To see if yttrium-90 daclizumab, high-dose chemotherapy, and stem cell transplants can treat HL that has not responded to earlier treatments.
Eligibility:
- Individuals at least 18 years of age who have Hodgkins lymphoma that has not responded to chemotherapy.
Design:
- Participants will be screened with a physical exam and medical history. They will also have blood and urine tests.
- Participants will have filgrastim and plerixafor to move stem cells into the blood. Stem cells will be collected with apheresis.
- Four weeks after stem cells are collected, participants will have the 90Y daclizumab and normal daclizumab to treat the HL. Chemotherapy will start 9 days after the first treatment.
- Most participants will have a second dose of 90Y daclizumab 6 weeks after the first dose.
- After each daclizumab treatment, participants will have several imaging studies of the chest and abdomen. Blood samples will also be collected.
- On the day after the last day of chemotherapy, participants will receive the stem cells collected earlier. Filgrastim injections will help stimulate stem cell growth....
详细描述
Background:
- Although Hodgkins lymphoma (HL) is considered a highly treatable cancer, patients with relapsed and chemotherapy refractory disease represent a major therapeutic challenge.
- Only 30-65% of relapsed patients will achieve long-term disease free survival with the current standard of care high-dose chemotherapy with autologous hematopoietic stem cell transplant (ASCT).
- The malignant Reed-Sternberg cells of HL and the surrounding benign T cell infiltrates often express CD25, the high affinity interleukin-2 receptor (IL-2R alpha).
- In study NCI-97-C-0110, we treated 30 patients with CD25-expressing relapsed or refractory HL with radioimmunotherapy (RIT) using (90)Y-labeled daclizumab (anti-CD25), and achieved a 63% response rate including 12 complete responses with few serious adverse events other than MDS in 4 patients.
- We propose integrating (90)Y-labeled daclizumab RIT into the induction regimen of ASCT in an effort to improve the response and disease-free survival in relapsed and refractory HL.
Objectives:
Phase I Primary Objectives:
- To assess the safety and adverse events associated with (90)Y-daclizumab (humanized anti-CD25) radioimmunotherapy (RIT) in combination with high-dose BEAM (carmustine, etoposide, cytarabine, [Ara-C, cytosine arabinoside] and melphalan) chemotherapy and autologous hematopoietic stem cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin s lymphoma (HL) with adverse prognostic factors.
- To determine the maximum tolerated dose in mCi of (90)Y-daclizumab RIT in combination with high-dose BEAM chemotherapy and ASCT in patients with relapsed or refractory HL.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Yttrium-90-labeled Daclizumab + Chemotherapy
Yttrium-90-labeled Daclizumab + BCNU, etoposide, cytarabine and melphalan (BEAM) + Auto stem cell transplant (ASCT)
干预措施: Auto stem cell transplant (Procedure)
Yttrium-90-labeled Daclizumab + Chemotherapy
Yttrium-90-labeled Daclizumab + BCNU, etoposide, cytarabine and melphalan (BEAM) + Auto stem cell transplant (ASCT)
干预措施: BEAM (Drug)
Yttrium-90-labeled Daclizumab + Chemotherapy
Yttrium-90-labeled Daclizumab + BCNU, etoposide, cytarabine and melphalan (BEAM) + Auto stem cell transplant (ASCT)
干预措施: 111In-daclizumab (Radiation)
Yttrium-90-labeled Daclizumab + Chemotherapy
Yttrium-90-labeled Daclizumab + BCNU, etoposide, cytarabine and melphalan (BEAM) + Auto stem cell transplant (ASCT)
干预措施: 90Y-daclizumab (Radiation)
结局指标
主要结局
Number of Participants With Adverse Events
时间窗: 30 months
Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Maximum Tolerated Dose (MTD) of 90Y-daclizumab With Carmustine, Etoposide, Cytarabine, [Ara-C, Cytosine Arabinoside] and Melphalan (BEAM) and Auto Stem Cell Transplant (ASCT): Phase I Portion
时间窗: Day 100 post autologous stem cell transplant
The MTD is defined as the dose level below the dose at which 2 out of 2 to 6 patients at a given dose level develop dose limiting toxicity (DLT). A DLT is defined as patients who develop either a Common Terminology Criteria in Adverse Events (CTCAE) v4.0 grade 3 or greater non-hematologic toxicity, with the exception of fatigue, of more than 5 days duration possibly, probably or definitely related to the infusion of 90Y-daclizumab prior to the start of BEAM chemotherapy (Day - 6) will have developed by definition a dose-limiting toxicity (DLT).
Number of Participants With A Dose Limiting Toxicity
时间窗: 30 months
Patients who develop either a Common Terminology Criteria in Adverse Events (CTCAE) v4.0 grade 3 or greater non-hematologic toxicity, with the exception of fatigue, of more than 5 days duration possibly, probably or definitely related to the infusion of 90Y-daclizumab prior to the start of Carmustine, Etoposide, Cytarabine, \[Ara-C, Cytosine Arabinoside\] and Melphalan (BEAM) chemotherapy (Day - 6) will have developed by definition a dose-limiting toxicity (DLT).
次要结局
- Overall Response Rate(Response is evaluated at day 100 post autologous stem cell transplant, then 1-4 times yearly for 5 years)
- Disease Free Survival (DFS)(DFS is evaluated at day 100 post autologous stem cell transplant, then 1-4 times yearly for 5 years)
- Overall Survival(OS is evaluated at day 100 post autologous stem cell transplant, then 1-4 times yearly for 5 years)
- Complete Response Rate(20 months post autologous stem cell transplant)
研究者
Kevin Conlon, MD
Principal Investigator
National Cancer Institute (NCI)