A Phase 2 Trial of Orca-T Following Reduced Intensity or Nonmyeloablative Conditioning in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 8
- 主要终点
- RIC Cohort: GVHD-free and relapse-free survival (GRFS)
研究概览
简要总结
This study will evaluate the safety, tolerability, and efficacy of Orca-T in participants undergoing reduced intensity or non-myeloablative allogeneic hematopoietic cell transplantation (alloHCT) for hematologic malignancies. Orca-T is 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).
详细描述
This study is a multicenter, open-label phase 2 trial of Orca-T in adults with acute myeloid leukemia or myelodysplastic syndrome who are not able to receive myeloablative (high intensity) conditioning and are eligible for reduced intensity conditioning (RIC)-alloHCT or non-myeloablative (NMA)-alloHCT with an 8/8 human leukocyte antigen (HLA)-matched related or unrelated donor. The trial is designed to further characterize the safety and tolerability of Orca-T and to perform an initial assessment of the efficacy of Orca-T in participants eligible for RIC-alloHCT or NMA-alloHCT.
Participants will receive Orca-T after the investigator's choice from the RIC and NMA regimens followed by single-agent graft-versus-host disease (GVHD) prophylaxis with tacrolimus.
Prior to the initiation of this study (the SERENE-T Study), a phase 1 study (clinicaltrials.gov number: NCT05088356) was conducted to examine the safety and efficacy of Orca-T in participants receiving RIC-alloHCT. Participants have also been treated previously with Orca-T during an ongoing phase 1b/3 study (NCT05316701 and NCT04013685) in participants receiving a MAC regimen. The results of these studies have prompted Orca Bio to further evaluate Orca-T in participants receiving RIC or NMA.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Age ≥18 years at the time of enrollment
- •Diagnosed with 1 of the following diseases:
- •Acute myeloid, 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 syndrome that is indicated for alloHCT per the 2017 International Expert Panel recommendations and/or therapy-related/secondary MDS as defined by the World Health Organization (WHO) classification of myeloid malignancies, with ≤10% blast burden in the bone marrow.
- •Planned to undergo 1 of the following preparative regimens as per Investigator discretion:
- •RIC cohort: Planned RIC-alloHCT including RIC regimen with TBI/thiotepa/fludarabine
- •NMA cohort: Planned NMA-alloHCT including NMA regimen with fludarabine/cyclophosphamide/TBI
- •Identified related or unrelated donor who is an 8/8 match for HLA-A, -B, -C, and -DRB1
- •Estimated glomerular filtration rate ≥30 mL/minute
- •Cardiac ejection fraction at rest ≥40% or shortening fraction of ≥22% by echocardiogram or radionuclide scan (MUGA)
- •Diffusing capacity of the lung for carbon monoxide (adjusted for hemoglobin) ≥40%
- •Negative serum or urine β-HCG test in persons of childbearing potential
- •Alanine transaminase (ALT)/aspartate transaminase (AST) <5 times the upper limit of normal (ULN)
- •Total bilirubin <3 × ULN
- •Deemed ineligible for a fully myeloablative alloHCT per assessment of the principal investigator
排除标准
- •Prior alloHCT
- •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 antidonor HLA antibodies against a mismatched allele in the selected donor
- •Karnofsky performance score <60%
- •For RIC cohort only: HCT-Specific Comorbidity Index (HCT-CI) ≥6
- •Uncontrolled bacterial, viral, or fungal infection (currently taking antimicrobial therapy and with progression or no clinical improvement) at the time of enrollment
- •Seropositive for HIV-1 or -2, HTLV-1 or -2, hepatitis B surface antigen, or HCV antibody unless previously treated with curative therapy and are HCV NAT negative
- •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 malignancy within 1 year except nonmelanoma skin cancer that has been curatively resected
- •Psychosocial circumstances that preclude the participant being able to go through transplantation or participate responsibly in follow-up care
- •Persons who are pregnant or breastfeeding
- •Person of childbearing potential (POCBP) or men who have sexual contact with POCBP who are unwilling to use effective forms of birth control or abstinence for 1 year after transplantation.
- •Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's or medical monitor's judgment, precludes the recipient's safe participation in and completion of the trial or which could affect compliance with the protocol or interpretation of results
研究组 & 干预措施
Orca-T
Participants will receive [RIC or NMA conditioning] + Orca-T + single-agent tacrolimus based on eligibility and investigator's choice of conditioning regimen.
干预措施: Orca-T (Biological)
结局指标
主要结局
RIC Cohort: GVHD-free and relapse-free survival (GRFS)
时间窗: Day 0 through day +365 after transplantation
GRFS is defined as the time from the date of transplantation to the date of death from any cause, relapse, the first onset of grade 3 or 4 acute GVHD (graded per MAGIC criteria), or the first onset of moderate or severe chronic GVHD (graded per NIH consensus criteria), whichever is earliest.
NMA Cohort: Incidence of neutrophil engraftment
时间窗: Day 0 through day +28 after transplantation
Incidence of neutrophil engraftment is defined as achieving an ANC ≥500/mm3 for 3 consecutive days by day +28. The first of the 3 days will be designated the day of engraftment. If the ANC never drops below 500/mm3, day +1 will be designated the day of engraftment.
RIC Cohort: GVHD-free and relapse-free survival (GRFS)
时间窗: Day 0 through day +365 after transplantation
GRFS is defined as the time from the date of transplantation to the date of death from any cause, relapse, the first onset of grade 3 or 4 acute GVHD (graded per MAGIC criteria), or the first onset of moderate or severe chronic GVHD (graded per NIH consensus criteria), whichever is earliest.
NMA Cohort: Incidence of neutrophil engraftment
时间窗: Day 0 through day +28 after transplantation
Incidence of neutrophil engraftment is defined as achieving an ANC ≥500/mm3 for 3 consecutive days by day +28. The first of the 3 days will be designated the day of engraftment. If the ANC never drops below 500/mm3, day +1 will be designated the day of engraftment.
NMA Cohort: Time to neutrophil engraftment
时间窗: Day 0 through day +28 after transplantation
The first of the 3 days will be designated the day of engraftment. If the ANC never drops below 500/mm3, day +1 will be designated the day of engraftment.
次要结局
- Incidence of serious infections(Day 0 through day +365 after transplantation)
- Incidence of platelet engraftment(Day 0 through day +50 after transplantation)
- Incidence of steroid-refractory acute GVHD(Day 0 through day +180 after transplantation)
- Incidence of steroid-refractory chronic GVHD(Day 0 through day +730 post-transplant)
- Overall survival(Day 0 through day +730 after transplantation)
- RIC cohort: Incidence of neutrophil engraftment(Day 0 through day +28 after transplantation)
- Time to onset of acute GVHD(Day 0 through day +180 after transplantation)
- RIC cohort: Time to neutrophil engraftment(Day 0 through day +28 after transplantation)
- RIC cohort: Incidence of neutrophil engraftment(Day 0 through day +28 after transplantation)
- Safety of Orca-T(Day 0 through day +100 after transplantation)
- Incidence of serious infections(Day 0 through day +365 after transplantation)
- Severity of serious infection(Day 0 through day +365 after transplantation)
- Overall survival(Day 0 through day +730 after transplantation)
- Non-relapse mortality(Day 0 through day +730 after transplantation)
- Relapse-free survival(Day 0 through day +730 after transplantation)
- Chronic GVHD-free survival(Day 0 through day +730 after transplantation)
- GVHD-free and relapse-free survival (GRFS)(Day 0 through day +730 after transplantation)
- Incidence of acute GVHD(Day 0 through day +180 after transplantation)
- Severity of acute GVHD(Day 0 through day +180 after transplantation)
- Time to onset of acute GVHD(Day 0 through day +730 after transplantation)
- Incidence of chronic GVHD(Day 0 through day +730 after transplantation)
- Severity of chronic GVHD(Day 0 through day +730 after transplantation)
- Incidence of platelet engraftment(Day 0 through day +50 after transplantation)
- Incidence of steroid-refractory acute GVHD(Day 0 through day +180 after transplantation)
- Incidence of steroid-refractory chronic GVHD(Day 0 through day +730 post-transplant)
- Time to platelet engraftment(Day 0 through day +50 after transplantation)