NCT06158828招募中1 期
A Phase I/II Pilot Study of Memory-like NK Cells to Consolidate TCRαβ T Cell Depleted Haploidentical Transplant in High-risk AML
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 68
- 试验地点
- 1
- 主要终点
- Safety of patients being administered donor-derived ML NK cells following TCR alpha beta depleted haploidentical cell transplant
研究概览
简要总结
This trial represents a single institution phase I/II pilot study with the primary objective of establishing the safety and feasibility of generating and infusing ML NK cells after TCRαβ haplo-HCT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Patient Inclusion Criteria - Cohort 1:
- •High risk acute myeloid leukemia (AML) in either:
- •Complete remission (CR) defined by < 5% marrow blasts by morphology in the context of hematological recovery (ANC ≥ 0.5× 10^9/L, platelet count ≥ 50 × 10^9/L).
- •Morphological leukemia free state (MLFS) defined by the absence of hematological recovery and < 5% marrow blasts by morphology
- •Patients must further meet one of the below for inclusion into the study:
- •De novo AML in CR1 with any of the following high-risk features:
- •MRD ≥ 1% after first induction course
- •MRD ≥ 0.1% after second induction course
- •RPN1-MECOM
- •RUNX1-MECOM
- •NPM1-MLF1
- •DEK-NUP214
- •KAT6A-CREBBP (if ≥ 90 days at diagnosis)
- •KMT2A-AFF1
- •KMT2A-AFDN
- •KMT2A-ABI1
- •KMT2A-MLLT1
- •11p15 rearrangement (NUP98 - any partner gene)
- •12p13.2 rearrangement (ETV6 - any partner gene)
- •Deletion 12p to include 12p13.2 (loss of ETV6)
- •Monosomy 5/Del(5q) to include 5q31 (loss of EGR1)
- •Monosomy 7
- •10p12.3 rearrangement (MLLT10 - any partner gene)
- •FLT3/ITD with allelic ratio > 0.1%, without bZIP CEBPA or NPM1
- •RAM phenotype as evidenced by flow cytometry
- •Other high-risk features not explicitly stated here, after discussion/approval with protocol PI.
- •De novo AML in ≥ CR2
- •Therapy-related AML in CR1
- •AML evolving from myelodysplastic syndrome (MDS)
- •One prior hematopoietic cell transplant is allowed, provided remission criteria as defined above are met.
- •Patient Inclusion Criteria - Cohort 2:
- •High risk acute myeloid leukemia (AML) defined by either of the following:
- •Treatment refractory disease: AML that is not in complete remission despite prior standard or salvage therapies.
- •Multiply relapsed disease: AML that has relapsed after 2 or more hematopoietic cell transplantations.
- •BM disease burden criteria:
- •Bone marrow blasts must be <25% by morphologic assessment on aspirate smear, based on a manual differential count of at least 200 nucleated cells.
- •If an absolute discrepancy of ≥ 20 percentage points exists between morphologic blast evaluation and ancillary studies - including flow cytometry, cytogenetics, and molecular analyses, eligibility determination is at the investigator's discretion.
- •Hypocellular / Aplastic Marrow Exception: If bone marrow cellularity on core biopsy is less than 25%, the blast percentage threshold and the 200-cell minimum differential count requirement are waived.
- •Patient Inclusion Criteria - Both Cohorts:
- •Less than or equal to 40 years of age.
- •Lansky (<16 years) or Karnofsky (≥16 years) performance status of >60%.
- •Adequate organ function as defined below:
- •Total bilirubin ≤ 3 x IULN for age
- •AST(SGOT)/ALT(SGPT) ≤ 5 x IULN for age
- •GFR ≥ 60 mL/min/1.73m2 as estimated by (1) updated Schwartz formula for ages 1-17 years or Cockcroft-Gault formula for ages ≥ 18 years, (2) 24-hour creatinine clearance, or (3) renal scintigraphy. If GFR is abnormal for age based on updated Schwartz or Cockcroft-Gault formula, accurate measurement should be obtained by either 24-hour creatinine clearance or renal scintigraphy.
- •Renal function may also be estimated by serum creatinine based on age/gender. A serum creatinine < 2 x IULN for age/gender is required for inclusion on this protocol.
- •Adequate cardiac function, defined by left ventricular ejection fraction (LVEF) at rest ≥50% or shortening fraction (SF) ≥27% (via echocardiogram or MUGA).
- •Adequate pulmonary function, defined by:
- •FEV1, FVC, and DLCO ≥50% of predicted.
- •O2 saturation ≥ 92% on room air by pulse oximetry and no supplemental O2 at rest for children < 8 years of age or those unable to perform pulmonary function testing (PFT). For children unable to perform PFT, a high-resolution CT chest should be obtained.
- 另有 5 项未显示
排除标准
- •Both Cohorts
- •Active GvHD. If patient had prior GvHD, patient must be off immunosuppression for at least 3 months prior to starting study treatment.
- •Active non-hematologic malignancy. History of other malignancy is acceptable as long as therapy has been completed and there is no current evidence of disease.
- •Currently receiving any other investigational agents at the time of transplant.
- •Active CNS or extramedullary disease. History of CNS or extramedullary disease currently in remission is acceptable.
- •A history of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in the study.
- •Inability to discontinue medications that are likely to interfere with ML NK cell activity, i.e., glucocorticoids and other immunosuppressants.
- •Presence of significant anti-donor HLA antibodies per institutional standards. Anti-donor HLA - Antibody Testing is defined as a positive crossmatch test of any titer (by complement dependent cytotoxicity or flow cytometric testing) or the mean fluorescence intensity (MFI) of any anti-donor HLA antibody by solid phase immunoassay >
- •Presence of a second major disorder deemed a contraindication for HCT.
- •Patients with Fanconi Anemia or Down Syndrome.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (bacterial, viral with clinical instability, or fungal), symptomatic congestive heart failure, or unstable cardiac arrhythmia.
- •Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of the start of conditioning.
- •Donor Eligibility Criteria - Both Cohorts
- •The preferred donor should be an adult aged 18 years or older. However, in circumstances where no suitable adult donor is available, consideration may be given to a minor donor aged 12 years or older. This exception only applies when all identified, otherwise eligible adult donors meet one or more of the following criteria:
- •A medical condition that poses unacceptable risk, including autoimmune disease, infection, hematologic disorder, malignancy or a pathogenic germline mutation.
- •Comorbidities that preclude safe administration of granulocyte colony-stimulating factor (G-CSF), placement of a pheresis catheter and/or stem cell collection.
- •Served as donor in prior haploidentical HCT.
- •Significant psychosocial or logistical barriers.
- •Donor must be HLA haploidentical (≥ 5/10 and ≤ 9/10 allele match at the -A, -B, -C, DRB1 and DQ loci) by high resolution typing and related to the patient.
- •Donor must meet the selection criteria as defined by the Foundation for the Accreditation of Hematopoietic Cell Therapy (FACT).
- •Donor must be available and willing to undergo one mobilized and one non-mobilized leukapheresis procedure.
- •Donor may not be pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days prior to initiation of recipient's conditioning regimen, within 7 days of donor stem cell mobilization regimen and prior to second non-mobilized leukapheresis..
- •Donor must be able to understand and willing to sign an IRB-approved written informed consent document.
研究组 & 干预措施
Donor
Other
Donors who meet the eligibility criteria will be mobilized as per institutional standard practice using G-CSF 10 mcg/kg/day for 5 consecutive days. Leukapheresis will be performed after 5 days of G-CSF administration (on Day -1) with a target volume for collection of 20 liters. If additional collection days are necessary to ensure target CD34+ doses, G-CSF administration may be extended per institutional standard and adjusted per physician discretion. Up to 4 days of pheresis are permitted.
干预措施: Plerixafor (Drug)
Donor
Other
Donors who meet the eligibility criteria will be mobilized as per institutional standard practice using G-CSF 10 mcg/kg/day for 5 consecutive days. Leukapheresis will be performed after 5 days of G-CSF administration (on Day -1) with a target volume for collection of 20 liters. If additional collection days are necessary to ensure target CD34+ doses, G-CSF administration may be extended per institutional standard and adjusted per physician discretion. Up to 4 days of pheresis are permitted.
干预措施: Granulocyte Colony-Stimulating Factor (Biological)
Cohort 1 Recipient: MAC or RIC + Cell graft + ML NK cell infusion
Experimental
- Patients with high-risk genetic features &/or poor response to upfront therapy
- Myeloablative Conditioning (MAC): rabbit antithymocyte globulin (rATG), Busulfan, Fludarabine, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7, followed by Busulfan and Fludarabine from days -6 to -3, & Thiotepa on day -2 OR
- Reduced Intensity Conditioning (RIC): rabbit antithymocyte globulin (rATG), Fludarabine, Melphalan, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7. Fludarabine is administered from day -8 to day -5, followed by Thiotepa on day -4 and Melphalan on days -3 and -2
- Patients will undergo infusion of the ex vivo TCRαβ/CD19+ depleted haploidentical HPC graft on day 0. On Day +7, patients will undergo infusion of the memory-like NK (ML NK) cells, followed by IL-2 subcutaneously 4 hours after the infusion. IL-2 will continue every other day through Day +19 for a maximum of 7 doses
干预措施: Rabbit Anti thymocyte globulin (Drug)
Cohort 1 Recipient: MAC or RIC + Cell graft + ML NK cell infusion
Experimental
- Patients with high-risk genetic features &/or poor response to upfront therapy
- Myeloablative Conditioning (MAC): rabbit antithymocyte globulin (rATG), Busulfan, Fludarabine, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7, followed by Busulfan and Fludarabine from days -6 to -3, & Thiotepa on day -2 OR
- Reduced Intensity Conditioning (RIC): rabbit antithymocyte globulin (rATG), Fludarabine, Melphalan, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7. Fludarabine is administered from day -8 to day -5, followed by Thiotepa on day -4 and Melphalan on days -3 and -2
- Patients will undergo infusion of the ex vivo TCRαβ/CD19+ depleted haploidentical HPC graft on day 0. On Day +7, patients will undergo infusion of the memory-like NK (ML NK) cells, followed by IL-2 subcutaneously 4 hours after the infusion. IL-2 will continue every other day through Day +19 for a maximum of 7 doses
干预措施: Busulfan (Drug)
Cohort 1 Recipient: MAC or RIC + Cell graft + ML NK cell infusion
Experimental
- Patients with high-risk genetic features &/or poor response to upfront therapy
- Myeloablative Conditioning (MAC): rabbit antithymocyte globulin (rATG), Busulfan, Fludarabine, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7, followed by Busulfan and Fludarabine from days -6 to -3, & Thiotepa on day -2 OR
- Reduced Intensity Conditioning (RIC): rabbit antithymocyte globulin (rATG), Fludarabine, Melphalan, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7. Fludarabine is administered from day -8 to day -5, followed by Thiotepa on day -4 and Melphalan on days -3 and -2
- Patients will undergo infusion of the ex vivo TCRαβ/CD19+ depleted haploidentical HPC graft on day 0. On Day +7, patients will undergo infusion of the memory-like NK (ML NK) cells, followed by IL-2 subcutaneously 4 hours after the infusion. IL-2 will continue every other day through Day +19 for a maximum of 7 doses
干预措施: Fludarabine (Drug)
Cohort 1 Recipient: MAC or RIC + Cell graft + ML NK cell infusion
Experimental
- Patients with high-risk genetic features &/or poor response to upfront therapy
- Myeloablative Conditioning (MAC): rabbit antithymocyte globulin (rATG), Busulfan, Fludarabine, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7, followed by Busulfan and Fludarabine from days -6 to -3, & Thiotepa on day -2 OR
- Reduced Intensity Conditioning (RIC): rabbit antithymocyte globulin (rATG), Fludarabine, Melphalan, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7. Fludarabine is administered from day -8 to day -5, followed by Thiotepa on day -4 and Melphalan on days -3 and -2
- Patients will undergo infusion of the ex vivo TCRαβ/CD19+ depleted haploidentical HPC graft on day 0. On Day +7, patients will undergo infusion of the memory-like NK (ML NK) cells, followed by IL-2 subcutaneously 4 hours after the infusion. IL-2 will continue every other day through Day +19 for a maximum of 7 doses
干预措施: Thiotepa (Drug)
Cohort 1 Recipient: MAC or RIC + Cell graft + ML NK cell infusion
Experimental
- Patients with high-risk genetic features &/or poor response to upfront therapy
- Myeloablative Conditioning (MAC): rabbit antithymocyte globulin (rATG), Busulfan, Fludarabine, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7, followed by Busulfan and Fludarabine from days -6 to -3, & Thiotepa on day -2 OR
- Reduced Intensity Conditioning (RIC): rabbit antithymocyte globulin (rATG), Fludarabine, Melphalan, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7. Fludarabine is administered from day -8 to day -5, followed by Thiotepa on day -4 and Melphalan on days -3 and -2
- Patients will undergo infusion of the ex vivo TCRαβ/CD19+ depleted haploidentical HPC graft on day 0. On Day +7, patients will undergo infusion of the memory-like NK (ML NK) cells, followed by IL-2 subcutaneously 4 hours after the infusion. IL-2 will continue every other day through Day +19 for a maximum of 7 doses
干预措施: TCR alpha beta / CD19+ depleted haploidentical hematopoietic progenitor cell graft (Biological)
Cohort 1 Recipient: MAC or RIC + Cell graft + ML NK cell infusion
Experimental
- Patients with high-risk genetic features &/or poor response to upfront therapy
- Myeloablative Conditioning (MAC): rabbit antithymocyte globulin (rATG), Busulfan, Fludarabine, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7, followed by Busulfan and Fludarabine from days -6 to -3, & Thiotepa on day -2 OR
- Reduced Intensity Conditioning (RIC): rabbit antithymocyte globulin (rATG), Fludarabine, Melphalan, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7. Fludarabine is administered from day -8 to day -5, followed by Thiotepa on day -4 and Melphalan on days -3 and -2
- Patients will undergo infusion of the ex vivo TCRαβ/CD19+ depleted haploidentical HPC graft on day 0. On Day +7, patients will undergo infusion of the memory-like NK (ML NK) cells, followed by IL-2 subcutaneously 4 hours after the infusion. IL-2 will continue every other day through Day +19 for a maximum of 7 doses
干预措施: memory-like natural killer cells (Biological)
Cohort 1 Recipient: MAC or RIC + Cell graft + ML NK cell infusion
Experimental
- Patients with high-risk genetic features &/or poor response to upfront therapy
- Myeloablative Conditioning (MAC): rabbit antithymocyte globulin (rATG), Busulfan, Fludarabine, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7, followed by Busulfan and Fludarabine from days -6 to -3, & Thiotepa on day -2 OR
- Reduced Intensity Conditioning (RIC): rabbit antithymocyte globulin (rATG), Fludarabine, Melphalan, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7. Fludarabine is administered from day -8 to day -5, followed by Thiotepa on day -4 and Melphalan on days -3 and -2
- Patients will undergo infusion of the ex vivo TCRαβ/CD19+ depleted haploidentical HPC graft on day 0. On Day +7, patients will undergo infusion of the memory-like NK (ML NK) cells, followed by IL-2 subcutaneously 4 hours after the infusion. IL-2 will continue every other day through Day +19 for a maximum of 7 doses
干预措施: IL-2 (Biological)
Cohort 1 Recipient: MAC or RIC + Cell graft + ML NK cell infusion
Experimental
- Patients with high-risk genetic features &/or poor response to upfront therapy
- Myeloablative Conditioning (MAC): rabbit antithymocyte globulin (rATG), Busulfan, Fludarabine, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7, followed by Busulfan and Fludarabine from days -6 to -3, & Thiotepa on day -2 OR
- Reduced Intensity Conditioning (RIC): rabbit antithymocyte globulin (rATG), Fludarabine, Melphalan, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7. Fludarabine is administered from day -8 to day -5, followed by Thiotepa on day -4 and Melphalan on days -3 and -2
- Patients will undergo infusion of the ex vivo TCRαβ/CD19+ depleted haploidentical HPC graft on day 0. On Day +7, patients will undergo infusion of the memory-like NK (ML NK) cells, followed by IL-2 subcutaneously 4 hours after the infusion. IL-2 will continue every other day through Day +19 for a maximum of 7 doses
干预措施: Plerixafor (Drug)
Cohort 1 Recipient: MAC or RIC + Cell graft + ML NK cell infusion
Experimental
- Patients with high-risk genetic features &/or poor response to upfront therapy
- Myeloablative Conditioning (MAC): rabbit antithymocyte globulin (rATG), Busulfan, Fludarabine, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7, followed by Busulfan and Fludarabine from days -6 to -3, & Thiotepa on day -2 OR
- Reduced Intensity Conditioning (RIC): rabbit antithymocyte globulin (rATG), Fludarabine, Melphalan, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7. Fludarabine is administered from day -8 to day -5, followed by Thiotepa on day -4 and Melphalan on days -3 and -2
- Patients will undergo infusion of the ex vivo TCRαβ/CD19+ depleted haploidentical HPC graft on day 0. On Day +7, patients will undergo infusion of the memory-like NK (ML NK) cells, followed by IL-2 subcutaneously 4 hours after the infusion. IL-2 will continue every other day through Day +19 for a maximum of 7 doses
干预措施: CliniMACS (Device)
Cohort 2 Recipient: MAC or RIC + Cell graft + ML NK cell infusion
Experimental
- Patients with high-risk AML who meet certain criteria listed in the protocol
- Myeloablative Conditioning (MAC): rabbit antithymocyte globulin (rATG), Busulfan, Fludarabine, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7, followed by Busulfan and Fludarabine from days -6 to -3, & Thiotepa on day -2 OR
- Reduced Intensity Conditioning (RIC): rabbit antithymocyte globulin (rATG), Fludarabine, Melphalan, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7. Fludarabine is administered from day -8 to day -5, followed by Thiotepa on day -4 and Melphalan on days -3 and -2
- Patients will undergo infusion of the ex vivo TCRαβ/CD19+ depleted haploidentical HPC graft on day 0. On Day +7, patients will undergo infusion of the memory-like NK (ML NK) cells, followed by IL-2 subcutaneously 4 hours after the infusion. IL-2 will continue every other day through Day +19 for a maximum of 7 doses
干预措施: Melphalan (Drug)
Cohort 2 Recipient: MAC or RIC + Cell graft + ML NK cell infusion
Experimental
- Patients with high-risk AML who meet certain criteria listed in the protocol
- Myeloablative Conditioning (MAC): rabbit antithymocyte globulin (rATG), Busulfan, Fludarabine, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7, followed by Busulfan and Fludarabine from days -6 to -3, & Thiotepa on day -2 OR
- Reduced Intensity Conditioning (RIC): rabbit antithymocyte globulin (rATG), Fludarabine, Melphalan, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7. Fludarabine is administered from day -8 to day -5, followed by Thiotepa on day -4 and Melphalan on days -3 and -2
- Patients will undergo infusion of the ex vivo TCRαβ/CD19+ depleted haploidentical HPC graft on day 0. On Day +7, patients will undergo infusion of the memory-like NK (ML NK) cells, followed by IL-2 subcutaneously 4 hours after the infusion. IL-2 will continue every other day through Day +19 for a maximum of 7 doses
干预措施: Rabbit Anti thymocyte globulin (Drug)
Cohort 2 Recipient: MAC or RIC + Cell graft + ML NK cell infusion
Experimental
- Patients with high-risk AML who meet certain criteria listed in the protocol
- Myeloablative Conditioning (MAC): rabbit antithymocyte globulin (rATG), Busulfan, Fludarabine, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7, followed by Busulfan and Fludarabine from days -6 to -3, & Thiotepa on day -2 OR
- Reduced Intensity Conditioning (RIC): rabbit antithymocyte globulin (rATG), Fludarabine, Melphalan, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7. Fludarabine is administered from day -8 to day -5, followed by Thiotepa on day -4 and Melphalan on days -3 and -2
- Patients will undergo infusion of the ex vivo TCRαβ/CD19+ depleted haploidentical HPC graft on day 0. On Day +7, patients will undergo infusion of the memory-like NK (ML NK) cells, followed by IL-2 subcutaneously 4 hours after the infusion. IL-2 will continue every other day through Day +19 for a maximum of 7 doses
干预措施: Busulfan (Drug)
Cohort 2 Recipient: MAC or RIC + Cell graft + ML NK cell infusion
Experimental
- Patients with high-risk AML who meet certain criteria listed in the protocol
- Myeloablative Conditioning (MAC): rabbit antithymocyte globulin (rATG), Busulfan, Fludarabine, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7, followed by Busulfan and Fludarabine from days -6 to -3, & Thiotepa on day -2 OR
- Reduced Intensity Conditioning (RIC): rabbit antithymocyte globulin (rATG), Fludarabine, Melphalan, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7. Fludarabine is administered from day -8 to day -5, followed by Thiotepa on day -4 and Melphalan on days -3 and -2
- Patients will undergo infusion of the ex vivo TCRαβ/CD19+ depleted haploidentical HPC graft on day 0. On Day +7, patients will undergo infusion of the memory-like NK (ML NK) cells, followed by IL-2 subcutaneously 4 hours after the infusion. IL-2 will continue every other day through Day +19 for a maximum of 7 doses
干预措施: Fludarabine (Drug)
Cohort 2 Recipient: MAC or RIC + Cell graft + ML NK cell infusion
Experimental
- Patients with high-risk AML who meet certain criteria listed in the protocol
- Myeloablative Conditioning (MAC): rabbit antithymocyte globulin (rATG), Busulfan, Fludarabine, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7, followed by Busulfan and Fludarabine from days -6 to -3, & Thiotepa on day -2 OR
- Reduced Intensity Conditioning (RIC): rabbit antithymocyte globulin (rATG), Fludarabine, Melphalan, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7. Fludarabine is administered from day -8 to day -5, followed by Thiotepa on day -4 and Melphalan on days -3 and -2
- Patients will undergo infusion of the ex vivo TCRαβ/CD19+ depleted haploidentical HPC graft on day 0. On Day +7, patients will undergo infusion of the memory-like NK (ML NK) cells, followed by IL-2 subcutaneously 4 hours after the infusion. IL-2 will continue every other day through Day +19 for a maximum of 7 doses
干预措施: Thiotepa (Drug)
Cohort 2 Recipient: MAC or RIC + Cell graft + ML NK cell infusion
Experimental
- Patients with high-risk AML who meet certain criteria listed in the protocol
- Myeloablative Conditioning (MAC): rabbit antithymocyte globulin (rATG), Busulfan, Fludarabine, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7, followed by Busulfan and Fludarabine from days -6 to -3, & Thiotepa on day -2 OR
- Reduced Intensity Conditioning (RIC): rabbit antithymocyte globulin (rATG), Fludarabine, Melphalan, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7. Fludarabine is administered from day -8 to day -5, followed by Thiotepa on day -4 and Melphalan on days -3 and -2
- Patients will undergo infusion of the ex vivo TCRαβ/CD19+ depleted haploidentical HPC graft on day 0. On Day +7, patients will undergo infusion of the memory-like NK (ML NK) cells, followed by IL-2 subcutaneously 4 hours after the infusion. IL-2 will continue every other day through Day +19 for a maximum of 7 doses
干预措施: TCR alpha beta / CD19+ depleted haploidentical hematopoietic progenitor cell graft (Biological)
Cohort 2 Recipient: MAC or RIC + Cell graft + ML NK cell infusion
Experimental
- Patients with high-risk AML who meet certain criteria listed in the protocol
- Myeloablative Conditioning (MAC): rabbit antithymocyte globulin (rATG), Busulfan, Fludarabine, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7, followed by Busulfan and Fludarabine from days -6 to -3, & Thiotepa on day -2 OR
- Reduced Intensity Conditioning (RIC): rabbit antithymocyte globulin (rATG), Fludarabine, Melphalan, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7. Fludarabine is administered from day -8 to day -5, followed by Thiotepa on day -4 and Melphalan on days -3 and -2
- Patients will undergo infusion of the ex vivo TCRαβ/CD19+ depleted haploidentical HPC graft on day 0. On Day +7, patients will undergo infusion of the memory-like NK (ML NK) cells, followed by IL-2 subcutaneously 4 hours after the infusion. IL-2 will continue every other day through Day +19 for a maximum of 7 doses
干预措施: memory-like natural killer cells (Biological)
Cohort 2 Recipient: MAC or RIC + Cell graft + ML NK cell infusion
Experimental
- Patients with high-risk AML who meet certain criteria listed in the protocol
- Myeloablative Conditioning (MAC): rabbit antithymocyte globulin (rATG), Busulfan, Fludarabine, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7, followed by Busulfan and Fludarabine from days -6 to -3, & Thiotepa on day -2 OR
- Reduced Intensity Conditioning (RIC): rabbit antithymocyte globulin (rATG), Fludarabine, Melphalan, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7. Fludarabine is administered from day -8 to day -5, followed by Thiotepa on day -4 and Melphalan on days -3 and -2
- Patients will undergo infusion of the ex vivo TCRαβ/CD19+ depleted haploidentical HPC graft on day 0. On Day +7, patients will undergo infusion of the memory-like NK (ML NK) cells, followed by IL-2 subcutaneously 4 hours after the infusion. IL-2 will continue every other day through Day +19 for a maximum of 7 doses
干预措施: IL-2 (Biological)
Cohort 2 Recipient: MAC or RIC + Cell graft + ML NK cell infusion
Experimental
- Patients with high-risk AML who meet certain criteria listed in the protocol
- Myeloablative Conditioning (MAC): rabbit antithymocyte globulin (rATG), Busulfan, Fludarabine, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7, followed by Busulfan and Fludarabine from days -6 to -3, & Thiotepa on day -2 OR
- Reduced Intensity Conditioning (RIC): rabbit antithymocyte globulin (rATG), Fludarabine, Melphalan, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7. Fludarabine is administered from day -8 to day -5, followed by Thiotepa on day -4 and Melphalan on days -3 and -2
- Patients will undergo infusion of the ex vivo TCRαβ/CD19+ depleted haploidentical HPC graft on day 0. On Day +7, patients will undergo infusion of the memory-like NK (ML NK) cells, followed by IL-2 subcutaneously 4 hours after the infusion. IL-2 will continue every other day through Day +19 for a maximum of 7 doses
干预措施: CliniMACS (Device)
结局指标
主要结局
Safety of patients being administered donor-derived ML NK cells following TCR alpha beta depleted haploidentical cell transplant
时间窗: From transplant through Day +100
Safety will be determined by events occurring following transplant. Non-relapse mortality, engraftment failure, and development of severe GvHD will be considered events.
Feasibility of manufacturing and administering donor-derived ML NK cells following TCR alpha beta depleted haploidentical cell transplant
时间窗: Through time of ML NK cell infusion (around Day +7)
Feasibility is defined by product manufacture failure, i.e., the inability to infuse ML NK cells due to product contamination or insufficient cell dose (\<0.5x10\^6 / kg recipient weight).
次要结局
- Development of acute graft versus host disease (aGvHD)(From transplant through Day +100)
- Analysis of immune reconstitution(From transplant through Month 24)
- Relapse Free Survival (RFS)(From transplant through Month 12)
- Development of chronic graft versus host disease (cGvHD)(From transplant through Day +365)
- Overall Survival (OS)(From transplant through Month 12)
- Development of infections(From transplant through Day +180)
- Development of chronic graft versus host disease (cGvHD)(From transplant through Day +180)
研究者
研究点 (1)
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