NCT03579875PHASE2Recruiting
Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders
Masonic Cancer Center, University of Minnesota
Start Date
11/13/2018
Completion Date
1/5/2029
Summary
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.
Eligibility Criteria
Age Range: No minimum to 65 years
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
Exclusion Criteria:
* 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
Interventions
DRUG
Total Body Irradiation (TBI) (Plan 1)
DRUG
Cyclophosphamide (CY) (Plan 1)
DRUG
Fludarabine (FLU)
DRUG
Methylprednisolone (MP)
DEVICE
Donor mobilized PBSC infusion
DRUG
G-CSF
DRUG
Cyclophosphamide (CY) (Plan 2)
DRUG
Rituximab
DRUG
Busulfan
DRUG
Alemtuzumab
DRUG
Melphalan
DRUG
Rituximab
Conditions
Fanconi AnemiaSevere Aplastic AnemiaMyelodysplastic SyndromesT Cell Receptor Alpha/Beta DepletionTelomere Biology DisorderBone Marrow FailureDyskeratosis CongenitaTelomere Biology Disorders
Locations
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota 55455
United States