NCT04872595进行中（未招募）2 期
Phase 2 Study of Personalized r-ATG Dosing to Improve Survival Through Enhanced Immune Reconstitution in Pediatric and Adult Patients Undergoing Ex-vivo CD34-Selected Allogeneic-HCT (PRAISE-IR)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 59
- 试验地点
- 1
- 主要终点
- proportion of patients who achieve CD4+IR
研究概览
简要总结
The purpose of this study is to see if conditioning regimens that include personalized rabbit ATG (P-rATG) help the immune system recover sooner and decrease the chances of transplant-related side effects. Participants in this study will be children and adults who have acute leukemia or myelodysplastic syndrome (MDS), and will receive a standard conditioning regimen to prepare the body for an allogeneic hematopoietic cell transplant (allo-HCT). The conditioning regimen will include r-ATG, one of two combinations of chemotherapy, and possibly total body irradiation (TBI).
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
- 4 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients receiving first peripheral blood mobilized ex-vivo CD34-selected T cell depleted allo-HCT for the following hematologic malignant conditions:
- •Acute myeloid leukemia (AML) with intermediate or high-risk features in CR1 or Relapse AML in ≥ CR
- •Must have MRD <5% (flow cytometry, molecular and/or cytogenetics accepted).
- •Acute leukemias of ambiguous lineage in ≥ CR
- •Must have MRD <5% (flow cytometry, molecular and/or cytogenetics accepted).
- •Acute lymphoid leukemia (ALL) in CR1 with clinical, flow cytometric, or molecular features indicating a high risk for relapse, or ALL in ≥ CR
- •Adult Patients - recommended but not required to be MRDnegative (by flow cytometry, molecular and/or cytogenetics).
- •Pediatric Patients - Must be MRD-negative by flow cytometry, molecular and/or cytogenetics.
- •Myelodysplastic syndromes (MDS) with least one of the following:
- •Revised International Prognostic Scoring System risk score of intermediate or higher at the time of transplant evaluation.
- •Life-threatening cytopenia.
- •Karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia, including abnormalities of chromosome 7 or 3, mutations of TP53, or complex or monosomal karyotype.
- •Therapy related disease or disease evolving from other malignant processes.
- •Able to tolerate cytoreduction
- •Patients age:
- •Regimen A: 4 - 60 years
- •Regimen B - no age restriction
- •Adequate organ function is required, defined as follows:
- •Hepatic: Serum bilirubin ≤ 2 mg/dL, unless benign congenital hyperbilirubinemia. Patients with hyperbilirubinemia related to paroxysmal nocturnal hemoglobinuria or other hemolytic disorders are eligible with PI approval.
- •Hepatic: AST, ALT, and alkaline phosphatase < 2.5 times the upper limit of normal unless thought to be disease-related.
- •Renal: serum creatinine <1.5x normal for age. If serum creatinine is outside the normal range, then CrCl > 50 mL/min/1.73m2 (calculated or estimated) or GFR (mL/min/1.72m2) >30% of predicted normal for age.
- •Normal GFR by Age
- •1 week 40.6 + / - 14.8
- •2 - 8 weeks 65.8 + / - 24.8
- •°> 8 weeks 95.7 +/- 21.7
- •2 - 12 years 133 +/- 27
- •13 - 21 years (males) 140 +/- 30
- •13 - 21 years (females) 126.0 + / - 22.0
- •Cardiac: LVEF ≥ 50% by MUGA or resting echocardiogram.
- •Pulmonary: Pulmonary function testing (FEV1 and corrected DLCO) ≥ 50% predicted (pediatric patients unable to complete PFTs will need oxygen saturation as recorded by pulse oximetry of ≥92% on room air).
- •Adequate performance status:
- •Age ≥ 16 years: ECOG ≤ 1 or Karnofsky 70%
- •Age < 16 years: Lansky 70%
- •Each patient must be willing to participate as a research subject and must sign an informed consent form or legal guardian with assent as appropriate.
排除标准
- •Patients with active extramedullary disease.
- •Patients with active central nervous system malignancy.
- •Uncontrolled infection at the time of allo-HCT.
- •Patients who have undergone previous allo-HCT.
- •Patient seropositivity for HIV I/II and/or HTLV I/II.
- •Females who are pregnant or breastfeeding.
- •Patients unwilling to use contraception during the study period.
- •Patient or parent or guardian unable to give informed consent or unable to comply with the treatment protocol including research tests.
- •Donor Inclusion Criteria:
- •Related or Unrelated Donors:
- •°8/8 HLA matched at A, B, C, and DRB1 loci, as tested by DNA analysis.
- •Able to provide informed consent for the donation process per institutional standards.
- •Meet standard criteria for donor collection (e.g. National Marrow Donor Program Guidelines or collecting center guidelines as approved by treating physician).
- •Provide GSCF mobilized peripheral blood stem cells
研究组 & 干预措施
P-rATG with total body irradiation, thiotepa, cyclophosphamide
Experimental
P-rATG days (always starting on Day -12 to -10)
- Hyper fractionated total body irradiation (1375 - 1500cGy*) Day -9 to -6
- Thiotepa (5mg/kg/day x 2 day) Day -5 to -4
- Cyclophosphamide (60mg/kg/day x 2 days) Day -3 to -2
- GCSF Day +7 *TBI dose in 125cGy fractions (with lung shielding) and total dose to be determined by treating physician/radiation oncology and is based off age, stage of disease, and anesthesia requirements.
干预措施: Personalized rATG (P-rATG) (Other)
P-rATG with total body irradiation, thiotepa, cyclophosphamide
Experimental
P-rATG days (always starting on Day -12 to -10)
- Hyper fractionated total body irradiation (1375 - 1500cGy*) Day -9 to -6
- Thiotepa (5mg/kg/day x 2 day) Day -5 to -4
- Cyclophosphamide (60mg/kg/day x 2 days) Day -3 to -2
- GCSF Day +7 *TBI dose in 125cGy fractions (with lung shielding) and total dose to be determined by treating physician/radiation oncology and is based off age, stage of disease, and anesthesia requirements.
干预措施: GCSF (Drug)
P-rATG with total body irradiation, thiotepa, cyclophosphamide
Experimental
P-rATG days (always starting on Day -12 to -10)
- Hyper fractionated total body irradiation (1375 - 1500cGy*) Day -9 to -6
- Thiotepa (5mg/kg/day x 2 day) Day -5 to -4
- Cyclophosphamide (60mg/kg/day x 2 days) Day -3 to -2
- GCSF Day +7 *TBI dose in 125cGy fractions (with lung shielding) and total dose to be determined by treating physician/radiation oncology and is based off age, stage of disease, and anesthesia requirements.
干预措施: Hyper fractionated total body irradiation (Radiation)
P-rATG with busulfan, melphalan and fludarabine
Experimental
P-rATG days (Appendix A - always starting on Day -12 to -10)
- Busulfan -Day -9 to -7
- Initial dose per table in Appendix B; doses 2-3 to be adjusted per PK for target cumulative exposure of 65 mg*h/L Melphalan (70mg/m2/day x 2 days) Day -6 to -5
- Fludarabine (25mg/m2/day x 5 days) Day -6 to -2
- GCSF Day +7
干预措施: Personalized rATG (P-rATG) (Other)
P-rATG with busulfan, melphalan and fludarabine
Experimental
P-rATG days (Appendix A - always starting on Day -12 to -10)
- Busulfan -Day -9 to -7
- Initial dose per table in Appendix B; doses 2-3 to be adjusted per PK for target cumulative exposure of 65 mg*h/L Melphalan (70mg/m2/day x 2 days) Day -6 to -5
- Fludarabine (25mg/m2/day x 5 days) Day -6 to -2
- GCSF Day +7
干预措施: GCSF (Drug)
P-rATG with total body irradiation, thiotepa, cyclophosphamide
Experimental
P-rATG days (always starting on Day -12 to -10)
- Hyper fractionated total body irradiation (1375 - 1500cGy*) Day -9 to -6
- Thiotepa (5mg/kg/day x 2 day) Day -5 to -4
- Cyclophosphamide (60mg/kg/day x 2 days) Day -3 to -2
- GCSF Day +7 *TBI dose in 125cGy fractions (with lung shielding) and total dose to be determined by treating physician/radiation oncology and is based off age, stage of disease, and anesthesia requirements.
干预措施: Cyclophosphamide (Drug)
P-rATG with total body irradiation, thiotepa, cyclophosphamide
Experimental
P-rATG days (always starting on Day -12 to -10)
- Hyper fractionated total body irradiation (1375 - 1500cGy*) Day -9 to -6
- Thiotepa (5mg/kg/day x 2 day) Day -5 to -4
- Cyclophosphamide (60mg/kg/day x 2 days) Day -3 to -2
- GCSF Day +7 *TBI dose in 125cGy fractions (with lung shielding) and total dose to be determined by treating physician/radiation oncology and is based off age, stage of disease, and anesthesia requirements.
干预措施: Thiotepa (Drug)
P-rATG with busulfan, melphalan and fludarabine
Experimental
P-rATG days (Appendix A - always starting on Day -12 to -10)
- Busulfan -Day -9 to -7
- Initial dose per table in Appendix B; doses 2-3 to be adjusted per PK for target cumulative exposure of 65 mg*h/L Melphalan (70mg/m2/day x 2 days) Day -6 to -5
- Fludarabine (25mg/m2/day x 5 days) Day -6 to -2
- GCSF Day +7
干预措施: Busulfan (Drug)
P-rATG with busulfan, melphalan and fludarabine
Experimental
P-rATG days (Appendix A - always starting on Day -12 to -10)
- Busulfan -Day -9 to -7
- Initial dose per table in Appendix B; doses 2-3 to be adjusted per PK for target cumulative exposure of 65 mg*h/L Melphalan (70mg/m2/day x 2 days) Day -6 to -5
- Fludarabine (25mg/m2/day x 5 days) Day -6 to -2
- GCSF Day +7
干预措施: Melphalan (Drug)
P-rATG with busulfan, melphalan and fludarabine
Experimental
P-rATG days (Appendix A - always starting on Day -12 to -10)
- Busulfan -Day -9 to -7
- Initial dose per table in Appendix B; doses 2-3 to be adjusted per PK for target cumulative exposure of 65 mg*h/L Melphalan (70mg/m2/day x 2 days) Day -6 to -5
- Fludarabine (25mg/m2/day x 5 days) Day -6 to -2
- GCSF Day +7
干预措施: Fludarabine (Drug)
结局指标
主要结局
proportion of patients who achieve CD4+IR
时间窗: within 100 days of HCT
is defined at CD4+ \> 50u/L at two consecutive measures within 100 days post allo-HCT.
次要结局
- Overall Survival (OS)(2 years)
研究者
研究点 (1)
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