PRESERVE: A Multi-Center Trial Using Banked, Cryopreserved HLA-Mismatched Unrelated Donor Bone Marrow and Post-Transplantation Cyclophosphamide in Allogeneic Transplantation for Patients With Hematologic Malignancies
概览
- 阶段
- 1 期
- 干预措施
- Cyclophosphamide
- 疾病 / 适应症
- Acute Leukemia
- 发起方
- Ossium Health, Inc.
- 主要终点
- Neutrophil engraftment
- 状态
- 撤回
- 最后更新
- 2个月前
概览
简要总结
Multicenter single arm study to assess the safety and efficacy of allogeneic transplantation using cryopreserved bone marrow from deceased MMUD and PTCy, sirolimus and MMF for GVHD prophylaxis.
研究者
入排标准
入选标准
- •Provision of signed and dated informed consent form
- •Stated willingness to comply with all study procedures and availability for the duration of the study
- •Male or female, aged ≥ 18 and \< 71 years (Note: HIV-negative subjects with MDS must be aged \<50 at the time of signing the informed consent form)
- •Diagnosed with
- •Acute leukemias or T-lymphoblastic lymphoma (T-LBL) in 1st or subsequent CR
- •Acute lymphocytic leukemia (ALL) or T-LBL as defined by the following:
- •\< 5% blasts in the bone marrow
- •Normal maturation of all cellular components in the bone marrow
- •No currently active extramedullary disease (EMD) (e.g., central nervous system (CNS), soft tissue disease)
- •ANC ≥ 1,000/mm3
排除标准
- •Pediatric patients (17 years or younger)
- •Suitable HLA-matched related or 8/8 allele matched (HLA-A, -B, -C, -DRB1) unrelated donor excluding Ossium product
- •Autologous HCT \< 3 months prior to the time of signing the informed consent form
- •Pregnancy or lactation
- •Treatment with an investigational drug or other interventional GVHD clinical trials
- •Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings)
- •Prior allogeneic HCT
- •Primary myelofibrosis or myelofibrosis secondary to essential thrombocythemia or polycythemia vera
- •Subjects with MDS may not receive RIC and must be \< 50 years of age at the time of signing the informed consent form
- •Any condition(s) or diagnosis, both physical or psychological, or physical exam finding that in the investigator's opinion precludes participation
研究组 & 干预措施
Regmin A (RIC)
Pre-transplant conditioning treatment with Fludarabine, Cyclophosphamide, and Total Body Irradiation (TBI)
干预措施: Cyclophosphamide
Regmin A (RIC)
Pre-transplant conditioning treatment with Fludarabine, Cyclophosphamide, and Total Body Irradiation (TBI)
干预措施: Fludarabine
Regmin A (RIC)
Pre-transplant conditioning treatment with Fludarabine, Cyclophosphamide, and Total Body Irradiation (TBI)
干预措施: Total Body Irradiation
Regmin A (RIC)
Pre-transplant conditioning treatment with Fludarabine, Cyclophosphamide, and Total Body Irradiation (TBI)
干预措施: Mesna
Regmin A (RIC)
Pre-transplant conditioning treatment with Fludarabine, Cyclophosphamide, and Total Body Irradiation (TBI)
干预措施: Sirolimus
Regmin A (RIC)
Pre-transplant conditioning treatment with Fludarabine, Cyclophosphamide, and Total Body Irradiation (TBI)
干预措施: Mycophenolate Mofetil
Regmin A (RIC)
Pre-transplant conditioning treatment with Fludarabine, Cyclophosphamide, and Total Body Irradiation (TBI)
干预措施: Filgrastim
Regmin A (RIC)
Pre-transplant conditioning treatment with Fludarabine, Cyclophosphamide, and Total Body Irradiation (TBI)
干预措施: Bone Marrow Transplant
Regimen B (FIC)
Pre-transplant conditioning treatment with Busulfan and Cyclophosphamide OR Fludarabine
干预措施: Cyclophosphamide
Regimen B (FIC)
Pre-transplant conditioning treatment with Busulfan and Cyclophosphamide OR Fludarabine
干预措施: Fludarabine
Regimen B (FIC)
Pre-transplant conditioning treatment with Busulfan and Cyclophosphamide OR Fludarabine
干预措施: Busulfan
Regimen B (FIC)
Pre-transplant conditioning treatment with Busulfan and Cyclophosphamide OR Fludarabine
干预措施: Mesna
Regimen B (FIC)
Pre-transplant conditioning treatment with Busulfan and Cyclophosphamide OR Fludarabine
干预措施: Sirolimus
Regimen B (FIC)
Pre-transplant conditioning treatment with Busulfan and Cyclophosphamide OR Fludarabine
干预措施: Mycophenolate Mofetil
Regimen B (FIC)
Pre-transplant conditioning treatment with Busulfan and Cyclophosphamide OR Fludarabine
干预措施: Filgrastim
Regimen B (FIC)
Pre-transplant conditioning treatment with Busulfan and Cyclophosphamide OR Fludarabine
干预措施: Bone Marrow Transplant
Regimen C (FIC)
Pre-transplant conditioning treatment with Cyclophosphamide and Total Body Irradiation (TBI)
干预措施: Cyclophosphamide
Regimen C (FIC)
Pre-transplant conditioning treatment with Cyclophosphamide and Total Body Irradiation (TBI)
干预措施: Total Body Irradiation
Regimen C (FIC)
Pre-transplant conditioning treatment with Cyclophosphamide and Total Body Irradiation (TBI)
干预措施: Mesna
Regimen C (FIC)
Pre-transplant conditioning treatment with Cyclophosphamide and Total Body Irradiation (TBI)
干预措施: Sirolimus
Regimen C (FIC)
Pre-transplant conditioning treatment with Cyclophosphamide and Total Body Irradiation (TBI)
干预措施: Mycophenolate Mofetil
Regimen C (FIC)
Pre-transplant conditioning treatment with Cyclophosphamide and Total Body Irradiation (TBI)
干预措施: Filgrastim
Regimen C (FIC)
Pre-transplant conditioning treatment with Cyclophosphamide and Total Body Irradiation (TBI)
干预措施: Bone Marrow Transplant
结局指标
主要结局
Neutrophil engraftment
时间窗: Day 35 Post HCT
Run-in safety phase primary endpoint; Neutrophil engraftment is defined as neutrophil recovery by Day 35. Neutrophil recovery is defined as donor-derived absolute neutrophil count (ANC) ≥ 500/mm3 for three consecutive days with evidence of donor chimerism in bone marrow or peripheral blood. Full donor chimerism is \>95%, and mixed donor chimerism is defined as 5-95%.
Overall survival (OS)
时间窗: 1-year Post HCT
Main phase primary endpoint; The primary endpoint for the study is OS at 1-year post-HCT. The event is death from any cause. The time to this event is the time from HCT to death, loss to follow-up, or end of study (whichever comes first). Subjects who are lost to follow-up prior to 1-year will be censored at the time of the last observation, and the OS probability will be estimated using the Kaplan-Meier method.
Cumulative incidence and kinetics of neutrophil and platelet recovery
时间窗: Day 35 Post HCT
Main phase primary endpoint; Neutrophil recovery is defined as achieving an absolute neutrophil count (ANC) greater than or equal to 500/mm3 for three consecutive measurements on three different days. The first of the three days will be designated the day of neutrophil recovery. The competing event is death without neutrophil recovery. For subjects who never drop ANC below 500/mm3, the date of neutrophil recovery will be Day 1 post-transplant. Platelet recovery is defined by two different metrics: the first day of a sustained platelet count greater than or equal to 20,000/mm3 or greater than or equal to 50,000/mm3 with no platelet transfusions in the preceding seven days. The first day of sustained platelet count above these thresholds will be designated the day of platelet engraftment. For subjects who never drop their platelet count below 20,000/mm3, the date of platelet recovery will be Day 1 post HCT.
次要结局
- Donor chimerism(Days 35, 56, 100, 180, and 1-year Post HCT)
- Cumulative incidence of cytokine release syndrome (CRS)(Day 14 Post HCT)
- Cumulative incidences of aGVHD and cGVHD(1-year Post HCT)
- NK, B- and T-cell immune reconstitution(Days 35, 100, 180, and 1-year Post HCT)
- Event free survival (EFS)(1-year Post HCT)
- GVHD relapse free survival (GRFS)(1-year Post HCT)
- Transplant-related mortality (TRM)(Day 100 and 1-year Post HCT)
- Progression free survival (PFS)(1-year Post HCT)
- Cumulative incidence of primary disease relapse/progression(1-year Post HCT)
- Cumulative incidences of viral reactivations and infections(Days 100, 180, and 1-year Post HCT)