Parallel Phase II Trial of IPA Targeted Adoptive Immunotherapy vs Adult Haplo-identical Cell Infusion During Induction of High Risk Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Safety of Cellular Immunotherapy as Measured by the Number of Participants Who Developed of Cytokine Release Syndrome (CRS) or Graft-versus-host Disease (GVHD) After Adoptive Immunotherapy
研究概览
简要总结
The purpose of this study is to determine the overall safety of adoptive immunotherapy when given after chemotherapy for AML/MDS. Adoptive immunotherapy means using an infusion of cells from a donor to help fight cancer. The donor cells will be either from the umbilical cord blood (UCB) of a newborn baby or they will be cells collected from a relative (haplo-identical cells).
The 2 cohorts that were discussed - adoptive immunotherapy with either UCB or haplo-identical stem cells - will be analyzed separately.
Preliminary data from other centers has suggested that adoptive immunotherapy with cells from a relative is an effective approach that may improve remission rates and survival in AML and MDS, because they exert anti-cancer effects of their own (so called graft vs leukemia effects) and possibly because they hasten recovery of cell counts from chemotherapy. The Investigators are interested in confirming these data, but also in testing umbilical cord blood cells for the same purpose. Preliminary data indicate that umbilical cord blood cells may have more powerful graft vs leukemia effects and cause fewer side-effects.
详细描述
This is a phase 2 trial to evaluate the safety of adoptive immunotherapy with Non-Inherited Maternal Antigen (NIMA) compatible, Inherited Paternal Antigen (IPA) targeted CBU or with haplo-identical stem cells after conventional induction therapy for very high risk Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS).
The study has 2 cohorts - patients in cohort 1 will receive CBU cells as adoptive immunotherapy. Patients in cohort 2 will receive haplo-identical cells. Both cohorts will be evaluated separately and no formal statistical comparison between cohorts will be performed.
There will be approximately 20 patients in each cohort, and a 95% confidence interval for the proportion of patients experiencing grade III-IV GVHD complications or unexplained prolonged myelosuppression complications in each cohort can be constructed to be within +/- 13.1% of the observed complication proportions. This calculation assumes an expected prevalence of each of these complication proportions of no greater than 10%.
After 10 patients are enrolled in each group, the incidence of the above-defined life-threatening complications will be assessed. If more than one patient out of 10 enrolled patients (i.e., greater than 10%) in a cohort experiences either of these complications, the cohort will be stopped for safety.
All potential recipients will have complete HLA typing and determination of HLA antibodies. An appropriate umbilical cord blood unit (CBU) will be identified or in the absence of an appropriate CBU, a haplo-identical donor will be identified.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 be 18 years of age or older
- •Patients with a confirmed diagnosis of AML or MDS, according to World Health Organization (WHO) classification (excluding acute promyelocytic leukaemia) with recurrent or refractory disease as defined below.
- •Primary induction failure (PIF) after ≥ 2 cycles of chemotherapy.
- •First relapse.
- •Relapse refractory to salvage chemotherapy
- •Second or subsequent relapse.
- •For MDS, either refractory anemia with excess blasts (RAEB) I or RAEB II who failed at least one chemotherapy regimen including either cytarabine or a hypomethylating agent.
- •Patients must have Karnofsky Performance score of ≥70
- •Women of child-bearing potential must have a negative serum or urine pregnancy test within 2 weeks prior to treatment start
- •Patients must be capable of understanding and complying with protocol requirements, and must be able and willing to sign a written informed consent form
排除标准
- •Persistent clinically significant toxicities from previous chemotherapy
- •Known positive status for human immunodeficiency virus (HIV)
- •Pregnant and nursing patients
- •Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, or psychiatric illness/social situations that would limit compliance with study requirements
- •Impairment of hepatic or renal function to such an extent that the patient, in the opinion of the investigator, will be exposed to an excessive risk if entered into this clinical study
- •Active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, or uncontrolled congestive heart failure. Any New York Heart Association (NYHA) grade 3 or
- •Any medical condition which in the opinion of the investigator places the patient at an unacceptably high risk for toxicities
结局指标
主要结局
Safety of Cellular Immunotherapy as Measured by the Number of Participants Who Developed of Cytokine Release Syndrome (CRS) or Graft-versus-host Disease (GVHD) After Adoptive Immunotherapy
时间窗: 6 months
Evaluate the safety of adoptive immunotherapy with Non-Inherited Maternal Antigen (NIMA) compatible, Inherited Paternal Antigen (IPA) targeted CBU or with haplo-identical stem cells after conventional induction therapy for very high risk AML or MDS. Assessed by development of cytokine release syndrome (CRS) or graft-versus-host disease (GVHD) after adoptive immunotherapy.
次要结局
- Number of Participants With Detectable Cord Blood or Haploidentical Chimerism After Adoptive Immunotherapy(6 months)
- Number of Participants Who Developed GVHD by Severity(6 months)
- Number of Participants That Underwent a Transplant After Response to Adoptive Immunotherapy(6 months)
- Number of Participants Who Responded to Treatment(6 months)
- Number of Participants With HLA-antibodies That Precluded Them From Moving Forward to Transplant(6 months)