NCT03579875招募中2 期
MT2017-17:T Cell Receptor Alpha/Beta T Cell Depleted Hematopoietic Cell Transplantation in Patients With Inherited Bone Marrow Failure (BMF) Disorders
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Grade II-IV acute graft versus host disease (GVHD)
研究概览
简要总结
This is a phase II trial of T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell (PBSC) transplantation in patients with inherited bone marrow failure (BMF) disorders to eliminate the need for routine graft-versus-host disease (GVHD) immune suppression leading to earlier immune recovery and potentially a reduction in the risk of severe infections after transplantation.
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
- — 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient Selection:
- •Inclusion Criteria:
- •For FA patients:
- •Diagnosis of Fanconi anemia
- •Age <65 years of age
- •Has one of the following risk factors:
- •Severe aplastic anemia (SAA)
- •Myelodysplastic features
- •High risk genotype
- •Immunodeficiency associated with history of recurrent infections
- •Karnofsky performance status ≥ 70% if ≥ 16 years of age or Lansky play score ≥ 50% for patients <16 years of age
- •Adequate pulmonary, cardiac and liver function
- •Voluntary written consent (minor assent if appropriate) prior to the performance of any study related procedures not part of standard medical care
- •For TBD patients:
- •Diagnosis of TBD
- •Age <70 years of age
- •Has one of the following risk factors:
- •Severe aplastic anemia (SAA)
- •Myelodysplastic features
- •Karnofsky performance status ≥ 70% if ≥ 16 years of age or Lansky play score
- •≥ 50% for patients <16 years of age
- •Adequate pulmonary, cardiac and liver function
- •Voluntary written consent (minor assent if appropriate) prior to the performance of any study related procedures not part of standard medical care
排除标准
- •Pregnant or breastfeeding as the treatment used in this study are Pregnancy Category D. Females of childbearing potential must have a negative pregnancy test (serum or urine) within 14 days of study registration
- •Active, uncontrolled infection within 1 week prior to starting study therapy
- •Malignant solid tumor cancer within previous 2 years
- •Donor Selection (Inclusion Criteria): meets one of the following match criteria:
- •an HLA-A, B, DRB1 matched sibling donor (matched sibling)
- •an HLA-A, B, DRB1 matched related donor (other than sibling)
- •a related donor mismatched at 1 HLA-A, B, C and DRB1 antigen
- •7-8/8 HLA-A,B,C,DRB1 allele matched unrelated donor per current institutional guidelines Patients and donors are typed for HLA-A and B using serological or molecular techniques and for DRB1 using high resolution molecular typing. If a donor has been selected on the basis of HLA-A, B, C and DRB1 typing as above, preference will be made for donors matched at the HLA-C locus.
- •Body weight of at least 40 kilograms and at least 12 years of age
- •Willing and able to undergo mobilized peripheral blood apheresis
- •In general good health as determined by the medical provider
- •Adequate organ function defined as:
- •Hematologic: hemoglobin, WBC, platelet within 10% of upper and lower limit of normal range of test (gender based for hemoglobin)
- •Hepatic: ALT < 2 x upper limit of normal
- •Renal: serum creatinine < 1.8 mg/dl
- •Performance of a donor infectious disease screen panel including CMV Antibody, Hepatitis B Surface Antigen, Hepatitis B Core Antibody, Hepatitis C Antibody, HIV 1/2 Antibody, HTLVA 1/2 Antibody, Treponema, and Trypanosoma Cruzi (T. Cruzi) plus HBV, HCV, WNV, HIV by nucleic acid testing (NAT); and screening for evidence of and risks factors for infection with Zika virus, or per current standard institutional donor screen - must be negative for HIV and active hepatitis B
- •Not pregnant - females of childbearing potential must have a negative pregnancy test within 7 days of mobilization start
- •Voluntary written consent (parent/guardian and minor assent, if < 18 years) prior to the performance of any research related procedure
研究组 & 干预措施
Treatment Plan 1: TBI 300 , CY, FLU, MP, Rituximab in patients with Fanconi Anemia
Experimental
Given to:
- Patients with an unrelated donor or HLA mismatched related donor, regardless of disease type OR
- Patients with an HLA- identical sibling donor recipient and myelodysplastic features, MDS, or acute leukemia
干预措施: Total Body Irradiation (TBI) (Plan 1) (Drug)
Treatment Plan 1: TBI 300 , CY, FLU, MP, Rituximab in patients with Fanconi Anemia
Experimental
Given to:
- Patients with an unrelated donor or HLA mismatched related donor, regardless of disease type OR
- Patients with an HLA- identical sibling donor recipient and myelodysplastic features, MDS, or acute leukemia
干预措施: Cyclophosphamide (CY) (Plan 1) (Drug)
Treatment Plan 1: TBI 300 , CY, FLU, MP, Rituximab in patients with Fanconi Anemia
Experimental
Given to:
- Patients with an unrelated donor or HLA mismatched related donor, regardless of disease type OR
- Patients with an HLA- identical sibling donor recipient and myelodysplastic features, MDS, or acute leukemia
干预措施: Fludarabine (FLU) (Drug)
Treatment Plan 1: TBI 300 , CY, FLU, MP, Rituximab in patients with Fanconi Anemia
Experimental
Given to:
- Patients with an unrelated donor or HLA mismatched related donor, regardless of disease type OR
- Patients with an HLA- identical sibling donor recipient and myelodysplastic features, MDS, or acute leukemia
干预措施: Methylprednisolone (MP) (Drug)
Treatment Plan 1: TBI 300 , CY, FLU, MP, Rituximab in patients with Fanconi Anemia
Experimental
Given to:
- Patients with an unrelated donor or HLA mismatched related donor, regardless of disease type OR
- Patients with an HLA- identical sibling donor recipient and myelodysplastic features, MDS, or acute leukemia
干预措施: Donor mobilized PBSC infusion (Device)
Treatment Plan 1: TBI 300 , CY, FLU, MP, Rituximab in patients with Fanconi Anemia
Experimental
Given to:
- Patients with an unrelated donor or HLA mismatched related donor, regardless of disease type OR
- Patients with an HLA- identical sibling donor recipient and myelodysplastic features, MDS, or acute leukemia
干预措施: G-CSF (Drug)
Treatment Plan 1: TBI 300 , CY, FLU, MP, Rituximab in patients with Fanconi Anemia
Experimental
Given to:
- Patients with an unrelated donor or HLA mismatched related donor, regardless of disease type OR
- Patients with an HLA- identical sibling donor recipient and myelodysplastic features, MDS, or acute leukemia
干预措施: Rituximab (Drug)
Treatment Plan 2: CY, FLU, MP, Rituximab in patients with Fanconi Anemia
Experimental
Given to:
• An HLA-identical sibling donor recipients with single or multi- lineage hematopoietic failure
干预措施: Fludarabine (FLU) (Drug)
Treatment Plan 2: CY, FLU, MP, Rituximab in patients with Fanconi Anemia
Experimental
Given to:
• An HLA-identical sibling donor recipients with single or multi- lineage hematopoietic failure
干预措施: Methylprednisolone (MP) (Drug)
Treatment Plan 2: CY, FLU, MP, Rituximab in patients with Fanconi Anemia
Experimental
Given to:
• An HLA-identical sibling donor recipients with single or multi- lineage hematopoietic failure
干预措施: Donor mobilized PBSC infusion (Device)
Treatment Plan 2: CY, FLU, MP, Rituximab in patients with Fanconi Anemia
Experimental
Given to:
• An HLA-identical sibling donor recipients with single or multi- lineage hematopoietic failure
干预措施: G-CSF (Drug)
Treatment Plan 2: CY, FLU, MP, Rituximab in patients with Fanconi Anemia
Experimental
Given to:
• An HLA-identical sibling donor recipients with single or multi- lineage hematopoietic failure
干预措施: Cyclophosphamide (CY) (Plan 2) (Drug)
Treatment Plan 2: CY, FLU, MP, Rituximab in patients with Fanconi Anemia
Experimental
Given to:
• An HLA-identical sibling donor recipients with single or multi- lineage hematopoietic failure
干预措施: Rituximab (Drug)
Treatment Plan 3: BU, Cy, FLU, MP and Rituximab in patients with Fanconi Anemia
Experimental
Given to:
- Patients with an unrelated donor or HLA mismatched related donor, regardless of disease type who cannot tolerate TBI
- Patients with an HLA- identical sibling donor recipient and myelodysplastic features, MDS, or acute leukemia who cannot tolerate TBI
- Biallelic mutations in FANCD1/BRCA2 who cannot receive TBI
- Per treating physician preference
干预措施: Cyclophosphamide (CY) (Plan 1) (Drug)
Treatment Plan 3: BU, Cy, FLU, MP and Rituximab in patients with Fanconi Anemia
Experimental
Given to:
- Patients with an unrelated donor or HLA mismatched related donor, regardless of disease type who cannot tolerate TBI
- Patients with an HLA- identical sibling donor recipient and myelodysplastic features, MDS, or acute leukemia who cannot tolerate TBI
- Biallelic mutations in FANCD1/BRCA2 who cannot receive TBI
- Per treating physician preference
干预措施: Fludarabine (FLU) (Drug)
Treatment Plan 3: BU, Cy, FLU, MP and Rituximab in patients with Fanconi Anemia
Experimental
Given to:
- Patients with an unrelated donor or HLA mismatched related donor, regardless of disease type who cannot tolerate TBI
- Patients with an HLA- identical sibling donor recipient and myelodysplastic features, MDS, or acute leukemia who cannot tolerate TBI
- Biallelic mutations in FANCD1/BRCA2 who cannot receive TBI
- Per treating physician preference
干预措施: Methylprednisolone (MP) (Drug)
Treatment Plan 3: BU, Cy, FLU, MP and Rituximab in patients with Fanconi Anemia
Experimental
Given to:
- Patients with an unrelated donor or HLA mismatched related donor, regardless of disease type who cannot tolerate TBI
- Patients with an HLA- identical sibling donor recipient and myelodysplastic features, MDS, or acute leukemia who cannot tolerate TBI
- Biallelic mutations in FANCD1/BRCA2 who cannot receive TBI
- Per treating physician preference
干预措施: Rituximab (Drug)
Treatment Plan 3: BU, Cy, FLU, MP and Rituximab in patients with Fanconi Anemia
Experimental
Given to:
- Patients with an unrelated donor or HLA mismatched related donor, regardless of disease type who cannot tolerate TBI
- Patients with an HLA- identical sibling donor recipient and myelodysplastic features, MDS, or acute leukemia who cannot tolerate TBI
- Biallelic mutations in FANCD1/BRCA2 who cannot receive TBI
- Per treating physician preference
干预措施: Busulfan (Drug)
Treatment Plan 4: CY, FLU, and alemtuzumab
Experimental
given to TBD patients with:
- Bone marrow failure AND
- Any donor type including haploidentical (4/8) to 8/8-HLA matched related donor, or 7-8/8 HLA-matched unrelated donor Based on historical numbers, it is expected approximately 3 patients would be treated per year. Statistical outcomes will be descriptive.
干预措施: Cyclophosphamide (CY) (Plan 1) (Drug)
Treatment Plan 4: CY, FLU, and alemtuzumab
Experimental
given to TBD patients with:
- Bone marrow failure AND
- Any donor type including haploidentical (4/8) to 8/8-HLA matched related donor, or 7-8/8 HLA-matched unrelated donor Based on historical numbers, it is expected approximately 3 patients would be treated per year. Statistical outcomes will be descriptive.
干预措施: Fludarabine (FLU) (Drug)
Treatment Plan 4: CY, FLU, and alemtuzumab
Experimental
given to TBD patients with:
- Bone marrow failure AND
- Any donor type including haploidentical (4/8) to 8/8-HLA matched related donor, or 7-8/8 HLA-matched unrelated donor Based on historical numbers, it is expected approximately 3 patients would be treated per year. Statistical outcomes will be descriptive.
干预措施: Alemtuzumab (Drug)
Treatment Plan 5: CY, FLU, melphalan (MEL), and alemtuzumab.
Experimental
given to TBD patients with:
- Early myelodysplastic features (with or without cytogenetic abnormalities) AND
- Any donor type including haploidentical (4/8) to 8/8-HLA matched related donor, or 7-8/8 HLA-matched unrelated donor Based on historical numbers, it is expected approximately 2 patients would be treated per year. Statistical outcomes will be descriptive.
干预措施: Cyclophosphamide (CY) (Plan 1) (Drug)
Treatment Plan 5: CY, FLU, melphalan (MEL), and alemtuzumab.
Experimental
given to TBD patients with:
- Early myelodysplastic features (with or without cytogenetic abnormalities) AND
- Any donor type including haploidentical (4/8) to 8/8-HLA matched related donor, or 7-8/8 HLA-matched unrelated donor Based on historical numbers, it is expected approximately 2 patients would be treated per year. Statistical outcomes will be descriptive.
干预措施: Fludarabine (FLU) (Drug)
Treatment Plan 5: CY, FLU, melphalan (MEL), and alemtuzumab.
Experimental
given to TBD patients with:
- Early myelodysplastic features (with or without cytogenetic abnormalities) AND
- Any donor type including haploidentical (4/8) to 8/8-HLA matched related donor, or 7-8/8 HLA-matched unrelated donor Based on historical numbers, it is expected approximately 2 patients would be treated per year. Statistical outcomes will be descriptive.
干预措施: Alemtuzumab (Drug)
Treatment Plan 5: CY, FLU, melphalan (MEL), and alemtuzumab.
Experimental
given to TBD patients with:
- Early myelodysplastic features (with or without cytogenetic abnormalities) AND
- Any donor type including haploidentical (4/8) to 8/8-HLA matched related donor, or 7-8/8 HLA-matched unrelated donor Based on historical numbers, it is expected approximately 2 patients would be treated per year. Statistical outcomes will be descriptive.
干预措施: Melphalan (Drug)
结局指标
主要结局
Grade II-IV acute graft versus host disease (GVHD)
时间窗: Day 100
incidence of grade II-IV acute graft versus host disease (GVHD)
次要结局
- Regimen related toxicity(30 Days after transplant)
- Neutrophil engraftment(Day 42)
- Platelet engraftment(Day 42)
- Acute graft versus host disease (aGVHD)(Day 100)
- Chronic graft versus host disease (cGVHD)(1 Year after transplant)
- Bacterial, viral and fungal infections(1 Year after transplant)
- Opportunistic infections(100 Days after transplant)
- Overall survival (OS)(1 Year after transplant)
研究者
研究点 (1)
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