A Phase III, Multicenter, Randomized Controlled Study to Compare Safety and Efficacy of a Haploidentical HSCT and Adjunctive Treatment With ATIR101, a T-lymphocyte Enriched Leukocyte Preparation Depleted ex Vivo of Host Alloreactive T-cells, Versus a Haploidentical HSCT With Post-transplant Cyclophosphamide in Patients With a Hematologic Malignancy
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 63
- 试验地点
- 42
- 主要终点
- Graft-versus-host Disease-free, Relapse-free Survival (GRFS)
研究概览
简要总结
The primary objective of this study is to compare safety and efficacy of a haploidentical T-cell depleted HSCT and adjunctive treatment with ATIR101 versus a haploidentical T cell replete HSCT with post-transplant administration of high dose cyclophosphamide (PTCy) in patients with a hematologic malignancy. An additional objective of the study is to compare the effect of the two treatments on quality of life.
详细描述
Study CR-AIR-009 is a Phase III randomized controlled multicenter open-label study comparing two parallel groups. After signing informed consent, a total of 250 patients will be randomized in a 1:1 fashion to receive either a T-cell depleted hematopoietic stem cell transplantation (HSCT; CD34 selection) from a related, haploidentical donor, followed by ATIR101 infusion, or a T-cell replete HSCT, followed by a high dose of post-transplant cyclophosphamide (PTCy).
Randomization will use minimization to balance treatment groups with respect to underlying disease (AML, ALL, or MDS), Disease Risk Index (DRI; intermediate risk, high risk, or very high risk) and center. A stochastic treatment allocation procedure will be used so that the treatment assignment is random for all patients entered in the study.
Patients randomized in the ATIR101 group will receive a single ATIR101 dose of 2×10E6 viable T-cells/kg between 28 and 32 days after the HSCT. Patients randomized in the PTCy group will receive cyclophosphamide 50 mg/kg/day at 3 and 4/5 days after the HSCT. All patients will be followed up for at least 24 months post HSCT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Any of the following hematologic malignancies:
- •Acute myeloid leukemia (AML) in first cytomorphological remission (with < 5% blasts in the bone marrow) with Disease Risk Index (DRI) intermediate or above, or in second or higher cytomorphological remission (with < 5% blasts in the bone marrow)
- •Acute lymphoblastic leukemia (ALL) in first or higher remission (with < 5% blasts in the bone marrow)
- •Myelodysplastic syndrome (MDS): transfusion-dependent (requiring at least one transfusion per month), or intermediate or higher Revised International Prognostic Scoring System (IPSS-R) risk group
- •Clinical justification of allogeneic stem cell transplantation where a suitable HLA matched sibling or unrelated donor is unavailable in a timely manner
- •Availability of a related haploidentical donor with one fully shared haplotype and 2 to 4 mismatches at the HLA-A, -B, -C, and -DRB1 loci of the unshared haplotype, as determined by high resolution human leukocyte antigen (HLA)-typing
- •Karnofsky Performance Status (KPS) ≥ 70%
- •Male or female, age ≥ 18 years and ≤ 70 years. Patients aged ≥ 65 years must have a Sorror score ≤ 3
- •Patient weight ≥ 25 kg and ≤ 130 kg
- •Availability of a donor aged ≥ 16 years and ≤ 75 years who is eligible according to local requirements and regulations. Donors aged < 16 years are allowed if they are the only option for an HSCT, if they are permitted by local regulations, and if the IRB/IEC approves participation in the study.
- •For females of childbearing potential who are sexually active and males who have sexual contact with a female of childbearing potential: willingness to use of reliable methods of contraception (oral contraceptives, intrauterine device, hormone implants, contraceptive injection or abstinence) during study participation
- •Given written informed consent (patient and donor)
排除标准
- •Diagnosis of chronic myelomonocytic leukemia (CMML)
- •Availability of a suitable HLA-matched sibling or unrelated donor in a donor search
- •Prior allogeneic hematopoietic stem cell transplantation
- •Diffusing capacity for carbon monoxide (hemoglobin corrected DLCO) < 50% predicted
- •Left ventricular ejection fraction < 45% (evaluated by echocardiogram or MUGA scan)
- •Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2.5 × upper limit of normal (CTCAE grade 2)
- •Creatinine clearance < 50 ml/min (calculated or measured)
- •Positive pregnancy test or breastfeeding of patient or donor (women of childbearing age only)
- •Estimated probability of surviving less than 3 months
- •Known allergy to any of the components of ATIR101 (e.g., dimethyl sulfoxide)
- •Known hypersensitivity to cyclophosphamide or any of its metabolites
- •Any contraindication for GVHD prophylaxis with mycophenolate mofetil, cyclosporine A, or tacrolimus
- •Known presence of HLA antibodies against the non-shared donor haplotype
- •Positive viral test of the patient or donor for human immunodeficiency virus (HIV)-1, HIV-2, hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum, human T-lymphotropic virus (HTLV)-1 (if tested), HTLV-2 (if tested), West Nile virus (WNV; if tested), or Zika virus (if tested)
- •Any other condition that, in the opinion of the investigator, makes the patient or donor ineligible for the study
研究组 & 干预措施
PTCy
T-cell replete HSCT from a related, haploidentical donor, followed by IV infusion of post-transplant cyclophosphamide (PTCy) 50 mg/kg/day at 3 and 4/5 days after the HSCT
干预措施: Cyclophosphamide (Drug)
ATIR101
T-cell depleted HSCT from a related, haploidentical donor, followed by IV infusion with ATIR101 at a single dose of 2×10E6 viable T-cells/kg body weight between 28 and 32 days after the HSCT
干预措施: ATIR101 (Biological)
ATIR101
T-cell depleted HSCT from a related, haploidentical donor, followed by IV infusion with ATIR101 at a single dose of 2×10E6 viable T-cells/kg body weight between 28 and 32 days after the HSCT
干预措施: T-cell depleted HSCT from a related, haploidentical donor (Procedure)
PTCy
T-cell replete HSCT from a related, haploidentical donor, followed by IV infusion of post-transplant cyclophosphamide (PTCy) 50 mg/kg/day at 3 and 4/5 days after the HSCT
干预措施: T-cell replete HSCT from a related, haploidentical donor (Procedure)
结局指标
主要结局
Graft-versus-host Disease-free, Relapse-free Survival (GRFS)
时间窗: 24 months post-HSCT
Defined as the time until acute GVHD grade III/IV, chronic GVHD requiring systemic treatment, relapse, or death, whichever occurs first. Kaplan-Meier estimates (percentage of participants) of GRFS were calculated at 24 months post HSCT.
次要结局
- Progression-free Survival (PFS)(24 months post-HSCT)
- Overall Survival (OS)(24 months post-HSCT)
- Relapse-related Mortality (RRM)(Through study completion, at least two years post HSCT)
- Transplant-related Mortality (TRM)(24 months post-HSCT)