Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders

Launched by MASONIC CANCER CENTER, UNIVERSITY OF MINNESOTA · Jul 6, 2018

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment for patients with inherited bone marrow failure disorders, such as Fanconi Anemia and Severe Aplastic Anemia. The goal of the trial is to see if a specific type of stem cell transplant, called T cell receptor alpha/beta depletion (α/β TCD), can help patients recover their immune systems faster and reduce the risk of infections after the transplant. By using this method, the researchers hope to eliminate the need for standard treatments that prevent complications like graft-versus-host disease, where the donor's immune cells attack the recipient's body.

To be eligible for this trial, patients generally need to be under 65 (or under 70 for certain conditions) and have a diagnosis of one of the targeted disorders along with specific risk factors, such as severe aplastic anemia or a history of infections. Participants must also have good overall health and organ function. If someone joins the trial, they can expect close monitoring and support throughout the process, and they'll be contributing to important research that may improve outcomes for future patients with these serious conditions.

Gender

ALL

Eligibility criteria

• 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 syndrome (MDS)
• • 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 syndrome (MDS)
• • 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