A Phase I/II Study: Enhancing Donor Hematopoietic Cell Engraftment With Plerixafor in Myeloablative Allogeneic Hematopoietic Cell Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 41
- 试验地点
- 2
- 主要终点
- Time to Neutrophil Recovery
研究概览
简要总结
This phase I/II clinical trial will test the safety and the efficacy of post transplant administration of plerixafor in enhancing hematological recovery in humans. Patients who are appropriate candidates for myeloablative allogeneic stem cell transplantation from an HLA-matched sibling, matched unrelated donor or umbilical cord blood are eligible for enrollment. The investigators plan to enroll a total of 50 patients for this study (30 patients with HLA-matched sibling or matched unrelated donor transplant, and 20 patients with umbilical cord blood transplant). During phase I study, a small number of patients (3-6 patients from each group) will be enrolled to determine the safety of post transplant administration of plerixafor. Patients will receive plerixafor given at 240 µg/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment. Limiting toxicities are defined as primary or secondary graft failure, plerixafor-related severe premature ventricular arrhythmia or death. If safety criteria are met from the investigators phase I study, the investigators will proceed with phase II study to determine the efficacy of post transplant administration of plerixafor in enhancing haematological recovery. The experimental aspect of this study is the use of plerixafor and all other aspects of care will be in line with the standard of care. Both Phase I and Phase II patients will be combined for efficacy analysis, and data collected from this study will be compared with the investigators historical control. The results from this study will set the stage and provide the justification for a larger phase 3 trial.
详细描述
Recruitment to this trial will be stratified by donor type as HLA (human leukocyte antigen) matched sibling, matched unrelated donor or umbilical cord blood. Patients will be conditioned with a myeloablative regimen such as, but not limited to, total body irradiation and cyclophosphamide. The donor stem cell grafts will come from mobilized peripheral blood of 8/8 or 7/8 HLA-identical family members, 8/8 (HLA A, B, C, DRBeta1) allele-level matched unrelated donors, or dual umbilical cord blood grafts with at least 4 of 6 HLA matching at HLA A and B (low resolution) and DRBeta1 (at high resolution). The target CD34+ cell dose will be 5 X 10(6)/kg recipient ideal body weight. For HLA matched sibling or matched unrelated donor (MUD) transplants, all patients will receive a minimum of 2 X 10(6) CD 24+ cells/kg. For cord blood transplants, each unit will contain a minimum total nucleated cell count of of 1.5 X 10(7)/kg. Post-transplant GVHD (graft versus host disease) prophylaxis will be given per institutional standard.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 to 65 years.
- •8/8 or 7/8 HLA-identical matched sibling OR Allele level 8/8 (HLA-A, B, C, DR Beta1)matched unrelated donor or 4/6 or better HLA matched cord blood.
- •Patients with high risk hematologic malignancies who are appropriate candidates for a myeloablative allogeneic stem cell transplantation.
- •Patients with a history of CNS disease must have been treated and have no active CNS disease at the time of protocol treatment.
- •ECOG performance status < or equal to 2
- •Patients must have adequate function of other organ systems as measured by:
- •Creatinine clearance (by Cockcroft Gault equation) > or equal to 30ml/min. Hepatic transaminases (ALT/AST) < or equal to 4 x normal, bilirubin < or equal to 2.0 mg/dl.
- •Pulmonary function tests demonstrating FVC and FEV1 of > or equal to 50% of predicted for age and DLCO > or equal to 50% of predicted.
- •Ejection fraction of > or equal to 45% by echocardiogram, radionuclide scan or cardiac MRI.
- •Patients must be HIV negative.
- •Patients must not be pregnant.
排除标准
- •Patients with > 5% blasts in bone marrow or peripheral circulation.
- •Uncontrolled infection.
- •Class III or IV angina as per NYHA criteria.
研究组 & 干预措施
Transplant Recipients
Transplant recipients from matched sibling donors and dual cord donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
干预措施: Plerixafor (Drug)
结局指标
主要结局
Time to Neutrophil Recovery
时间窗: 100 Days post Transplant
leukocytes \> 500/ul on 2 consecutive days
Time to Platelet Recovery
时间窗: 100 Days Post Transplant
platelet \> 20,000/ul on 2 consecutive days
Plerixafor-associated Adverse Events
时间窗: 100 Days Post Transplant
次要结局
- Absolute Lymphocyte Count at Day 90(90 days)
- IL-12 at Day 30(30 days)
- Participants Experiencing Grade II-IV Acute Graft Versus Host Disease(100 days)
- CD3+ Cell Count at Day 90(90 Days)
- CD4 Cell Count at Day 90(90 days)
- CD8 Cell Count at Day 90(90 days)
- B Cell Count at Day 30(30 days)
- B Cell Count at Day 60(60 days)
- IL-12 at Day 7(7 days)
- IL-12 at Day 14(14 days)
- IFN Gamma at Day 7(7 days)
- IFN Gamma at Day 14(14 days)
- TNF-alpha at Day 7(7 days)
- TNF-alpha at Day 14(14 days)
- Transplant-related Mortality(100 Days Post Transplant)
- B Cell Count at Day 90(90 days)
- NK Cell Count at Day 90(90 days)
- IFN Gamma at Day 30(30 days)
- TNF-alpha at Day 30(30 days)
- CD4 Cell Count at Day 30(30 days)
- CD4 Cell Count at Day 60(60 days)
- CD8 Cell Count at Day 30(30 days)
- CD8 Cell Count at Day 60(60 days)
- NK Cell Count at Day 30(30 days)
- NK Cell Count at Day 60(60 days)
研究者
Mitchell Horwitz, MD
Assoc Professor of Medicine
Duke University