A Randomized Phase III Trial of Patients With Advanced Hematologic Malignancies Undergoing Allogeneic Hematopoietic Cell Transplantation With Either Orca-T, a T-cell-Depleted Graft With Additional Infusion of Conventional T Cells and Regulatory T Cells, or Standard-of-Care Allogeneic Graft
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 187
- 试验地点
- 19
- 主要终点
- Event-free at 12 Months for Moderate or Severe Chronic Graft-versus-Host-Disease-free Survival (cGFS) Per Endpoint Adjudication Committee (EAC)
研究概览
简要总结
This study will evaluate the safety, tolerability, and efficacy of Orca-T, an allogeneic stem cell and T-cell immunotherapy biologic manufactured for each patient (transplant recipient) from the mobilized peripheral blood of a specific, unique donor. It is composed of purified hematopoietic stem and progenitor cells (HSPCs), purified regulatory T cells (Tregs), and conventional T cells (Tcons) in participants undergoing myeloablative allogeneic hematopoietic cell transplant transplantation for hematologic malignancies.
This posting represents the Phase III component of Precision-T. The Precision-T Ph1b component is described under NCT04013685.
详细描述
Cross reference NCT04013685
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Matched to a related or unrelated donor who is an 8/8 match for HLA-A, -B, -C, and DRB1
- •Diagnosed with one of the following diseases:
- •Acute myeloid, lymphoid or mixed phenotype leukemia in complete remission (CR) or CR with incomplete hematologic recovery (CRi), with or without the presence of known minimal residual disease
- •Myelodysplastic syndromes (MDS) that are indicated for alloHSCT per 2017 International Expert Panel recommendations and/or have therapy-related/secondary MDS, with ≤ 10% blast burden in the bone marrow
- •Planned to undergo MA-alloHCT including one of the following myeloablative conditioning regimens:
- •TBI/Etoposide
- •Cardiac ejection fraction at rest ≥ 45% or shortening fraction of ≥ 27% by echocardiogram or radionuclide scan (MUGA)
- •Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50%
- •Negative serum or urine beta-HCG test in females of childbearing potential
- •ALT/AST < 3 times ULN
- •Recipients in screening must screen negative for SARS-CoV-2 RNA using a PCR-based test
- •Disease Risk Index (DRI) overall risk categorization of intermediate or high
- •Total bilirubin ≤ upper limit of normal (ULN)
- •Estimated glomerular filtration rate (eGFR) ≥ 60 mL/minute
排除标准
- •Prior allogeneic HCT
- •Currently receiving corticosteroids or other immunosuppressive therapy. Topical corticosteroids or oral systemic corticosteroid doses less than or equal to 10 mg/day are allowed.
- •Planned donor lymphocyte infusion (DLI)
- •Planned pharmaceutical in vivo or ex vivo T cell depletion
- •Recipient positive anti-donor HLA antibodies against a mismatched allele in the selected donor
- •Karnofsky performance score < 70%
- •Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) > 4
- •Uncontrolled bacterial, viral or fungal infections at time of enrollment
- •Seropositive for HIV-1 or -2, HTLV-1 or -2, Hepatitis B sAg, Hepatitis C antibody
- •Known allergy or hypersensitivity to, or intolerance of, tacrolimus
- •Documented allergy or hypersensitivity to iron dextran or bovine, murine, algal or Streptomyces avidinii proteins
- •Any uncontrolled autoimmune disease requiring active immunosuppressive treatment
- •Concurrent malignancies or active disease within 1 year, except non-melanoma skin cancers that have been curatively resected
- •Psychosocial circumstances that preclude the patient being able to go through transplant or participate responsibly in follow up care
- •Women who are pregnant or breastfeeding
- •Women of childbearing potential (WOCBP) or men who have sexual contact with WOCBP unwilling to use effective forms of birth control or abstinence for one year after transplantation
研究组 & 干预措施
Orca-T
For patients randomized to the Orca-T arm, Orca-T will be administered after myeloablative conditioning regimen. Single-agent GVHD prophylaxis with tacrolimus will be administered following Tcon infusion (generally Day +3).
干预措施: Orca-T (Biological)
Standard of Care alloHCT Control
For patients randomized to the standard-of-care control arm, an unmanipulated allograft derived from the peripheral blood of a matched donor will be administered after a myeloablative conditioning regimen. Dual-agent prophylaxis consisting of tacrolimus plus methotrexate will be administered starting on Day -3.
干预措施: Standard-of-Care (Biological)
结局指标
主要结局
Event-free at 12 Months for Moderate or Severe Chronic Graft-versus-Host-Disease-free Survival (cGFS) Per Endpoint Adjudication Committee (EAC)
时间窗: Day 0 through 730 days after transplantation
Event-free rate estimated at 12 months for cGFS per EAC, which is defined as the time from date of allogeneic hematopoietic cell transplantation (alloHCT) (ie, day 0) to date of death from any cause or first onset of moderate or severe chronic graft-versus-host disease (cGVHD) (graded per NIH consensus criteria), whichever was earliest, within 2 years after day 0. cGVHD was assessed and graded by EAC blinded to treatment assignment. Each participant in the study is followed for up to 730 days after transplant. Primary analysis was event driven (ie, when 56 participants had died or had moderate or severe cGVHD) and was not based on duration of follow-up. The analysis was conducted using all available data at the time that the 56th event occurred, and event-free rate at 12 months was estimated regardless of length of follow-up for individual participants. At the time of analysis, not all participants have reached 730 days of follow-up because they enrolled at different times.
次要结局
- Event Rate at 12 Months for Time to Moderate or Severe cGVHD Per EAC(Day 0 through 730 days after transplantation)
- Event-free at 12 Months for Overall Survival (OS)(Up to 730 days after end of enrollment)
- Event-free Rate at 12 Months for Graft-versus-host Disease-free and Relapse-free Survival (GRFS) Per EAC(Day 0 through 730 days after transplantation)