Pilot Study to Assess the Use of JSP191 in Matched Unrelated Donor Transplantation for Chronic Granulomatous Disease (CGD)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Early and long term engraftment
研究概览
简要总结
Background:
Chronic granulomatous disease (CGD) is a rare immune disorder that can cause serious infections throughout the body. The only cure for CGD is a stem cell transplant. Transplants from a sibling are best, but many people must get transplants from unrelated donors. However, these transplants can cause serious complications in people with CGD.
Objective:
To see if a study drug (JSP191) can help improve the success rates of stem cell transplants for people with CGD from an unrelated donor.
Eligibility:
People aged 4 to 65 years with CGD who require a transplant.
Design:
Participants will be screened. Part of the screening will help to identify the best match to a transplant donor. Participants will have a physical exam, including dental and eye exams. They will have blood and urine tests. They will have tests of their breathing and heart function. A bone marrow sample will be taken. They will have their stem cells collected.
Participants will have a catheter inserted into a vein in their chest. It will remain in place for the entire period of transplant and recovery.
Participants will be in the hospital 40 to 50 days for the transplant. This will include a conditioning phase, to prepare their body for the procedure, as well as the transplant and recovery phases. As part of the conditioning phase, participants will receive JSP191 through a vein for 1 hour.
After discharge, participants will have follow-up visits 2 times a week for 100 days. Additional follow-up visits will continue for 5 years....
详细描述
Study Description:
This is a pilot study for individuals with chronic granulomatous disease (CGD) using an unmanipulated matched unrelated donor (MUD) graft. The conditioning regimen will use alemtuzumab (Campath-1H, Genzyme Corporation) and total body irradiation (TBI) combined with the investigational new drug JSP191.
Participants will receive a high-dose donor graft infusion followed by post-transplant cyclophosphamide (Cytoxan, Baxter International, Inc). This study will determine whether replacing busulfan with the new investigational drug, JSP191, within the alemtuzumab/TBI-based conditioning regimen yields engraftment in patients with CGD.
Objectives:
Primary Objective:
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
- 4 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •INCLUSION CRITERIA:
- •Has confirmed CGD.
- •Has sufficient complications from underlying disease to warrant undergoing transplantation (either a history of or ongoing inflammation/CGD-related autoimmunity OR a CGD-related infection while on prophylaxis) OR has a Quartile 1 or 2 residual oxidase production level.
- •Aged 4 years to 65 years.
- •Has an unrelated matched donor available (but no matched related donor available).
- •Must be able to stay within 1 hours travel of the NIH for the first 3 months after transplantation and have a family member or other designated companion to stay with during the post-transplant period.
- •Must provide a durable power of attorney for health care decisions to an appropriate adult relative or guardian in accordance with form NIH 200 NIH Durable Power of Attorney for Health Care Decision Making.
- •If of childbearing potential, must agree to consistently use contraception from 1 month prior to baseline, throughout study participation, and for 1 year after receiving transplanted cells. Acceptable forms of contraception are:
- •Contraceptive pills or patch, Norplant, Depo-Provera, or other FDA-approved contraceptive method.
- •Male partner has previously undergone a vasectomy.
- •If able to impregnate a partner, must agree to consistently use contraception from the time of enrollment through 3 months post-transplant. Acceptable forms of contraception are:
- •Male condom with spermicide.
排除标准
- •Eastern Cooperative Oncology Group (ECOG) or equivalent performance status >= 3 (see Supportive Care guidelines, available at https://training.seer.cancer.gov/followup/procedures/dataset/ecog.html).
- •Left ventricular ejection fraction < 40%.
- •Transaminases > 5x upper limit of normal based on the individual s clinical situation and at the discretion of the investigator.
- •CRP > 100 mg/dL within 6 weeks of the transplant.
- •Psychiatric disorder or mental deficiency severe enough as to make compliance with the HSCT unlikely, and/or to make regulatorily and legally effective informed consent impossible.
- •Major anticipated illness or organ failure incompatible with survival from allogeneic HSCT.
- •Pregnant or breastfeeding.
- •HIV positive.
- •Uncontrolled seizure disorder.
- •Any condition or circumstance that the PI feels would create difficulty in maintaining compliance with the requirements of this protocol.
- •Individuals who are not willing to submit their information as part of the alemtuzumab (Campath) Distribution Program application or participants whom the Distribution Program committee has determined are not qualified to receive alemtuzumab.
- •NOTE: Alemtuzumab (IV formulation) is no longer distributed commercially. In order to receive product, the physician must contact the program for the patient. If the patient is not willing to consent to submit their information (demographics, contact information, and rationale for use) to the program such that we can obtain the drug, then we cannot proceed with conditioning; therefore, the individual will not be eligible for this protocol.
研究组 & 干预措施
Single arm study
Eligible CGD patients will receive one time infusion of study product along with Alemtuzumab and TBI as part of HSCT conditioning regimen
干预措施: JSP191 (Biological)
结局指标
主要结局
Early and long term engraftment
时间窗: Day 100 and 2 years post transplant
To determine the engraftment rates, both early and long term, when using JSP191 in conjunction with TBI, Alemtuzumab and post transplant cyclophosphamide and sirolimus for unrelated donor transplantation of patients with Chronic Granulomatous Disease.
次要结局
- Incidence of viral reactivation(Through study completion about 104 weeks)
- Incidence of graft-vs-host disease (GvHD)(Through study completion about 104 weeks)
- Safety(Through study completion about 104 Weeks)