Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders

Официальное название

MT2017-17:T Cell Receptor Alpha/Beta T Cell Depleted Hematopoietic Cell Transplantation in Patients With Inherited Bone Marrow Failure (BMF) Disorders

Обзор

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.

Вмешательства

• Препарат Total Body Irradiation (TBI) (Plan 1)
  300 cGy with thymic shielding on day -6
• Препарат Cyclophosphamide (CY) (Plan 1)
  10 mg/kg IV daily on days -5, -4, -3, and -2
• Препарат Fludarabine (FLU)
  35 mg/m2 IV daily on days -5, -4, -3, and -2
• Препарат Methylprednisolone (MP)
  1 mg/kg IV q12h on days -5, -4, -3, -2, and -1
• Устройство Donor mobilized PBSC infusion
  T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell (PBSC) transplantation on day 0
• Препарат G-CSF
  Initiate G-CSF 5mcg/kg per day IV on day +1 (continue until ANC \>2.5 x 10\^9/L for 3 consecutive days or single day ANC \>3000 Arm 1 and Arm 3)
• Препарат Cyclophosphamide (CY) (Plan 2)
  5 mg/kg IV daily on days -5, -4, -3, and -2
• Препарат Rituximab
  200 mg/m2 IV once on day -1
• Препарат Busulfan
  Busulfan 0.6 mg/kg if \> 4 years old and/or \>12 kg (0.8 mg/kg IV if ≤ 4 years old and/or ≤ 12 kg) is given IV over 2 hours every 12 hours for 2 days.
• Препарат Alemtuzumab
  Alemtuzumab 0.2 mg/kg is given IV over 2 hours daily for 5 days (total dose 1 mg/kg)

Первичные конечные точки

• Grade II-IV acute graft versus host disease (GVHD) [Срок оценки: Day 100]

Вторичные конечные точки (8)

• Neutrophil engraftment [Срок оценки: Day 42]
• Platelet engraftment [Срок оценки: Day 42]
• Acute graft versus host disease (aGVHD) [Срок оценки: Day 100]
• Chronic graft versus host disease (cGVHD) [Срок оценки: 1 Year after transplant]
• Regimen related toxicity [Срок оценки: 30 Days after transplant]
• Bacterial, viral and fungal infections [Срок оценки: 1 Year after transplant]
• Opportunistic infections [Срок оценки: 100 Days after transplant]
• Overall survival (OS) [Срок оценки: 1 Year after transplant]

Критерии участия

Patient Selection:

Критерии включения

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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Masonic Cancer Center at University of Minnesota — Minneapolis

Идентификаторы

NCT: NCT03579875 · 2016LS161 · MT2017-17

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗