Safety and Efficacy of Chemotherapy Combined With Adoptive Transfer of Human Leukocyte Antigen (HLA)-Haploidentical Donor Lymphocyte Infusion (DLI) in Older Patients With Righ-Risk Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Number of Subjects With Unacceptable Toxicity
研究概览
简要总结
The primary hypothesis is that chemotherapy followed by donor lymphocyte infusion (DLI) from HLA-haploidentical donors is a safe procedure that will not cause Graft versus Host Disease (GVHD) or increased treatment-related mortality. The Investigator further believes that this will improve outcomes of elderly patients with high-risk AML or MDS compared to chemotherapy alone, and that that this benefit will be even greater in donor-recipient pairs that share maternal-fetal microchimerism or non-inherited maternal antigen (NIMA) mismatch. A large part of this trial will include immune function assays as well as assessments of efficacy, toxicity, and GVHD. Because this therapy may be a tolerable alternative to allogeneic hematopoietic stem cell transplantation (alloHSCT) for elderly patients, the Investigator will validate functional measurements (e.g. Comprehensive Geriatric Assessment (CGA)) with biologic correlates (cytokine and genomic profiles) and clinical outcomes.
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
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must have their diagnosis of high-risk AML or high-risk MDS confirmed by pathologic review of bone marrow biopsy according to WHO guidelines
- •Patients will be defined as high risk AML and thus eligible if they meet one or more of the following criteria:
- •Secondary AML (from underlying MDS or therapy related)
- •Presence of complex cytogenetic abnormalities (3 or more cytogenetic abnormalities), all monosomies, del 5q, del 7q, inv3, t(3;3), t(6;9), t(9;22), abn 11q23 (excluding t(9;11))
- •Fms-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) mutation positive
- •Age ≥ 65 years given poor outcomes even with favorable cytogenetics
- •Patients will be defined as high risk MDS and thus eligible if they have a MD Anderson Comprehensive Cancer MDS Risk Score ≥9
- •Subjects must have Eastern Cooperative Oncology Group (ECOG) Performance status of 0,1,or 2; if ECOG 2, they must also have a Charlson comorbidity index of ≤
- •Subjects must be 55 years of age or older
- •Subjects should have a 3-5/6 HLA-matched related haploidentical donor who is evaluated and deemed able to provide DLI.
- •Patient should be able to provide informed consent
- •Subjects must have a multigated acquisition (MUGA) and /or ECHO or cardiac magnetic resonance imaging (MRI). The required minimum standards include MUGA or ECHO or cardiac MR showing an ejection fraction( EF) of 40%. Those with an EF 40-49% must also have a cardiologist consult and assist with management.
- •Pulmonary function tests (PFTs) with diffusing capacity of lung for carbon monoxide (DLCO) are conditional for subjects at the discretion of the physician. The required minimum standards for those who have PFTs include DLCO of 40%. Those with DLCO of 40-49% must have a pulmonologist consult and assist with management.
- •Subjects of all genders and races are eligible
排除标准
- •Pregnant or lactating women.
- •Patients with other major medical or psychiatric illnesses which the treating physician feels could seriously compromise tolerance to this protocol
- •Patients with known active central nervous system (CNS) disease
- •Patients with acute promyelocytic leukemia (FAB M3)
研究组 & 干预措施
Idarubicin + Cytarabine + DLI
Chemotherapy combined with adoptive transfer of HLA-haploidentical donor lymphocyte infusion (DLI)
干预措施: Idarubicin (Drug)
Idarubicin + Cytarabine + DLI
Chemotherapy combined with adoptive transfer of HLA-haploidentical donor lymphocyte infusion (DLI)
干预措施: Cytarabine (Drug)
Idarubicin + Cytarabine + DLI
Chemotherapy combined with adoptive transfer of HLA-haploidentical donor lymphocyte infusion (DLI)
干预措施: DLI (Biological)
结局指标
主要结局
Number of Subjects With Unacceptable Toxicity
时间窗: up to 8 weeks after last cell infusion
Unacceptable toxicity is defined as: i. Grade III or IV acute GVHD (aGVHD) of the gut or liver or Grade IV aGVHD of the skin lasting \> 7 days; ii. Grade IV Common Terminology Criteria for Adverse Events (CTCAE) toxicity attributable to DLI (e.g. infusion reaction, as opposed to Grade IV CTCAE toxicity from chemotherapy) and lasting \>7 days iii. Treatment-related mortality (TRM)
次要结局
- Overall Survival(2 years after completing therapy)
- Disease Free Survival(one year following adoptive transfer)
- Percentage of Subjects With Unacceptable Toxicity(8 weeks after the last cell infusion)
- Number of Days to Hematopoietic Recovery(2 years after completion of therapy)
- Rate of Efficacy(2 years after completing therapy)
- Percentage of Subjects With Acute GVHD(8 weeks after last cell infusion)
- Number of Participants With Immune Recovery(up to 2 years after completing therapy)