MT2021-08T Cell Receptor Alpha/Beta Depletion PBSC Transplantation for Heme Malignancies

Study Overview
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Brief Summary
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This is a phase II, open-label, prospective study of T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell (PBSC) transplantation for children and adults with hematological malignancies

Official Title
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Phase II, Open-Label, Prospective Study of T Cell Receptor Alpha/Beta Depletion (A/B TCD) Peripheral Blood Stem Cell (PBSC) Transplantation for Children and Adults With Hematological Malignancies

Conditions
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Hematologic Malignancy, Acute Leukemia, Remission, Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, AML, TP53, Intrachromosomal Amplification of Chromosome 21, Cytogenetic Abnormality, CNS Leukemia, Minimal Residual Disease, Myelodysplasia, Juvenile Myelomonocytic Leukemia, Somatic Mutation, PTPN11 Gene Mutation, N-RAS Gene Amplification, Neurofibromatosis 1, NF1 Mutation, CBL Gene Mutation, Monosomy 7, Chromosome Abnormality, Fetal Hemoglobin

Intervention / Treatment
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* Drug: Fludarabine
* Drug: Busulfan
* Drug: Melphalan
* Drug: Rituximab
* Drug: Levetiracetam


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen<br>Patients will be treated on the most medically appropriate regimen with a preference for Flu/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells. | Drug: Fludarabine<br>* Fludarabine 25mg/m2 IV on days -8 to -6 or days -4 to -2. 40mg/m2 IV on days -5 to -2.<br>Drug: Rituximab<br>* 200 mg/m2 intravenous given once on day-1<br>|
| Experimental: Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen<br>Patients will be treated on the most medically appropriate regimen with a preference for Flu/TBI Arm followed by an infusion at Day 0 of Alpha/Beta T Cell-Depleted Hematopoietic Stem Cells. | Drug: Fludarabine<br>* Fludarabine 25mg/m2 IV on days -8 to -6 or days -4 to -2. 40mg/m2 IV on days -5 to -2.<br>Drug: Busulfan<br>* Busulfan 82.1 mg*hr/L IV on days -5 to -2 or days -8 to -5<br>Drug: Rituximab<br>* 200 mg/m2 intravenous given once on day-1<br>Drug: Levetiracetam<br>* 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.<br>* Other names: Keppra;|
| Experimental: Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only<br>Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia. | Drug: Fludarabine<br>* Fludarabine 25mg/m2 IV on days -8 to -6 or days -4 to -2. 40mg/m2 IV on days -5 to -2.<br>Drug: Busulfan<br>* Busulfan 82.1 mg*hr/L IV on days -5 to -2 or days -8 to -5<br>Drug: Melphalan<br>* Melphalan 50 mg/m2 IV on days -4 to -2<br>Drug: Rituximab<br>* 200 mg/m2 intravenous given once on day-1<br>Drug: Levetiracetam<br>* 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.<br>* Other names: Keppra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the rate of GVHD after alpha beta TCR depletion | GVHD incidence after treatment. | 85 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transplant engraftment | Monitor median rate of engraftment by 42 days. | 42 days | 
| Graft Failure | Determine the rate of graft failure by day 100 (defined as lack of achievement of an ANC >=500/mL with associated pancytopenia) | 100 days | 
| Non-relapse mortality (NRM) | Determine the incidence of non-relapse mortality (NRM) at 100 days and 1 year | 12 months | 
| Overall survival (OS) | Number of participants experiencing progression free survival at one year follow up | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bu, Flu, G-CSF, GFSR, aGVHD, HCT, MAC, Mel, PBSCT, PTLD, RECIST, TCR