Patient case: 13-year-old male with acute myeloid leukemia; genetic feature: FLT3

Clinical trial: Phase I/II MAHCT w/ TCell Depleted Graft w/ Simultaneous Infusion Conventional and Regulatory T Cell

Summary: For patients with hematologic malignancies undergoing allogeneic myeloablative (MA) HCT with a T cell depleted graft, the infusion of naturally occurring regulatory T cells with conventional T cells (T cell addback) in pre-defined doses and ratios will reduce the incidence of acute graft vs host disease while augmenting the graft vs leukemia effect and improving immune reconstitution.


Eligibility: Recipient Inclusion Criteria
  1. Patients with the following diseases that are histopathologically confirmed are eligible
  -  Acute leukemia, primary refractory or beyond CR1
  -  High risk acute myeloid leukemia in CR1 with any of the following features:
  -  Complex karyotype(≥3 clonal chromosomal abnormalities)
  -  Any of the following high risk chromosomal abnormalities:
  -  Monosomal karyotype (-5, 5q-, -7, 7q-)
  -  t(11q23), t(9;11), inv(3), t(3;3) t(6;9) t(9;22)
  -  Normal karyotype with FLT3-ITD mutation
  -  Chronic myelogenous leukemia (accelerated, blast or second chronic phase)
  -  Myelodysplastic syndromes
  -  Myeloproliferative syndromes
  -  Non-Hodgkin lymphoma with poor risk features not suitable for autologous HCT
  2. Age >18 yo and < 60 yo for patients in Cohort 1 only. At the start of Cohort 2A and beyond, eligibility will be expanded to allow pediatric patients age >13 yo.
  3. Cardiac ejection fraction > 45%
  4. Lung diffusion capacity > 50%
  5. Calculated creatinine clearance > 50 cc/min
  6. SGPT and SGOT < 2.5 x ULN, unless elevated secondary to disease. Total bilirubin < 2 x ULN (patients with Gilbert's syndrome may be included at the discretion of the PI or where hemolysis has been excluded
  7. Availability of an 6/6 HLA matched sibling defined by Class I (HLA -A and B) serologic typing (or higher resolution) and Class II (HLA-DRB1) molecular typing.
  8. Karnofsky performance status >70%
  9. No prior myeloablative therapy or hematopoietic cell transplantation
  Recipient Exclusion Criteria
  1. Seropositive for any of the following: HIV ab, hepatitis B sAg , hep C ab
  2. Uncontrolled bacterial, viral or fungal infection defined as currently taking antimicrobial therapy and progression of clinical symptoms.
  3. Uncontrolled CNS disease involvement
  4. The recipient is pregnant or a lactating female.
  5. Psychosocial circumstances that preclude the patient being able to go through transplant or participate responsibly in follow up care
  Donor Inclusion Criteria
  1. Age >13 yo and < 75 years
  2. Karnofsky performance status of >70% defined by institutional standards
  3. Seronegative for HIV Ag, HIV 1 and HIV 2 ab, HTLV 1 and HTLV 2 ab hepatitis B sAg or PCR+ or hepatitis C ab or PCR+ , negative for the Syphillis treponemal screen and negative for HIV 1 and hepatitis C by NAT (nucleic acid testing) within 30 days of apheresis collection
  4. Must be 6/6 matched sibling donor as determined by HLA typing
  5. Female donors of child-bearing potential must have a negative serum or urine beta-HCG test within three weeks of mobilization
  6. Capable of undergoing leukapheresis, have adequate venous access, and be willing to undergo insertion of a central catheter should leukapheresis via peripheral vein be inadequate
  7. The donor or legal guardian greater than 18 years of age, capable of signing an IRB-approved consent form.
  8. Donor selection will be in compliance with 21 CFR 1271.
  Donor Exclusion Criteria
  1. Evidence of active infection or viral hepatitis
  2. HIV positive
  3. Lactating female

Relevance to patient case: not relevant