Acute Leukemia, Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, AML, CBL Gene Mutation, Chromosome Abnormality, CNS Leukemia, Cytogenetic Abnormality, Fetal Hemoglobin, Hematologic Malignancy, High Grade Non-Hodgkin's Lymphoma, Adult, Intrachromosomal Amplification of Chromosome 21, Juvenile Myelomonocytic Leukemia, Lymphoblastic Lymphoma, Minimal Residual Disease, Monosomy 7, Myelodysplasia, Neurofibromatosis 1, NF1 Mutation, N-RAS Gene Amplification, PTPN11 Gene Mutation, Remission, Somatic Mutation, TP53
Conditions
Keywords
Bu, Flu, G-CSF, GFSR, aGVHD, HCT, MAC, Mel, PBSCT, PTLD, RECIST, TCR
Brief summary
This is a phase II, open-label, prospective study of T cell receptor alpha/beta depletion (TCR α/β TCD) peripheral blood stem cell (PBSC) transplantation for children and adults with hematological malignancies. This is a safety/feasibility study of the investigational procedure/product.
Interventions
DRUGFludarabine
Fludarabine 25mg/m2 IV on days -8 to -6 or days -4 to -2. 40mg/m2 IV on days -5 to -2.
DRUGBusulfan
Busulfan 82.1 mg\*hr/L IV on days -5 to -2 or days -8 to -5
DRUGMelphalan
Melphalan 50 mg/m2 IV on days -4 to -2
DRUGRituximab
200 mg/m2 intravenous given once on day-1
DRUGLevetiracetam
As seizures have occurred following high dose busulfan, all patients will be treated with Keppra beginning day -6 and continuing until day -1 per institutional guidelines.
BIOLOGICALAlpha/Beta T Cell-Depleted Hematopoietic Stem Cells
Patients will be treated on the most medically appropriate regimen followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells.
DRUGThymoglobulin
rabbit anti-thymocyte globulin (rATG). Used in conditioning regimens for in vivo depletion of T cells, and the use of fludarabine model-based dosing to optimize dosing.
DRUGCyclophosphamide
Cyclophosphamide 60 mg/kg IV over 2 hours on days -3 and -2
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 60 Years
Healthy volunteers
No
Inclusion criteria
* Histological confirmation of hematological malignancies * Acute leukemias * Acute Myeloid Leukemia (AML) and related precursor neoplasms * Favorable risk AML is defined as having one of the following: * Acute lymphoblastic leukemia (ALL)/lymphoma * Myelodysplasia (MDS) IPSS INT-2 or High Risk (i.e. RAEB, RAEBt) or Refractory Anemia with severe pancytopenia, transfusion dependence, or high risk cytogenetics or molecular features. * Age 60 years of age or younger at the time of consent * Karnofsky performance status ≥ 70% or Lansky play score 50% for ≤16 years of age. * Adequate organ function
Exclusion criteria
* Pregnant or breastfeeding. * Active uncontrolled infection within 1 week of starting preparative therapy * Known seropositive for HIV or known active Hepatitis B or C infection with detectable viral load by PCR. * Any prior autologous or allogeneic transplant * CML blast crisis * Active central nervous system malignancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine the rate of GVHD after alpha beta TCR depletion | 100 days | GVHD incidence after treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Transplant engraftment | 42 days | Monitor median rate of engraftment by 42 days. |
| Graft Failure | 100 days | Determine the rate of graft failure by day 100 (defined as lack of achievement of an ANC \>=500/mL with associated pancytopenia) |
| Non-relapse mortality (NRM) | 12 months | Determine the incidence of non-relapse mortality (NRM) at 100 days and 1 year |
| Overall survival (OS) | 12 months | Number of participants experiencing progression free survival at one year follow up |
Countries
United States
Contacts
CONTACTMargaret MacMillan
PRINCIPAL_INVESTIGATORMargaret MacMillan
University of Minnesota Masonic Cancer Center
Outcome results
None listed