Back to resultsMT2021-08T Cell Receptor Alpha/Beta Depletion PBSC Transplantation for Heme Malignancies
Primary Purpose
Hematologic Malignancy, Acute Leukemia, Remission
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Fludarabine
Busulfan
Melphalan
Rituximab
Levetiracetam
Sponsored by
About this trial
This is an interventional treatment trial for Hematologic Malignancy focused on measuring Bu, Flu, G-CSF, GFSR, aGVHD, HCT, MAC, Mel, PBSCT, PTLD, RECIST, TCR
Eligibility Criteria
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
Sites / Locations
- University of Minnesota Masonic Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen
Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen
Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only
Arm Description
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.
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.
Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia.
Outcomes
Primary Outcome Measures
Determine the rate of GVHD after alpha beta TCR depletion
GVHD incidence after treatment.
Secondary Outcome Measures
Transplant engraftment
Monitor median rate of engraftment by 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)
Non-relapse mortality (NRM)
Determine the incidence of non-relapse mortality (NRM) at 100 days and 1 year
Overall survival (OS)
Number of participants experiencing progression free survival at one year follow up
Full Information
NCT ID
NCT05735717
First Posted
January 10, 2023
Last Updated
October 2, 2023
Sponsor
Masonic Cancer Center, University of Minnesota
1. Study Identification
Unique Protocol Identification Number
NCT05735717
Brief Title
MT2021-08T Cell Receptor Alpha/Beta Depletion PBSC Transplantation for Heme Malignancies
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 11, 2023 (Actual)
Primary Completion Date
November 30, 2027 (Anticipated)
Study Completion Date
November 30, 2030 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
Keywords
Bu, Flu, G-CSF, GFSR, aGVHD, HCT, MAC, Mel, PBSCT, PTLD, RECIST, TCR
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
150 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Fludarabine (flu), Total Body Irradiation (TBI), Flu/TBI Regimen
Arm Type
Experimental
Arm Description
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.
Arm Title
Fludarabine (flu), Busulfan (bu), Flu/Bu Regimen
Arm Type
Experimental
Arm Description
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.
Arm Title
Fludarabine (flu), Busulfan (bu), Melphalan (Mel) Regimen for Pediatric Patients Only
Arm Type
Experimental
Arm Description
Flu/Bu/Mel will the preference for patients with JMML or infants with leukemia.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Fludarabine 25mg/m2 IV on days -8 to -6 or days -4 to -2. 40mg/m2 IV on days -5 to -2.
Intervention Type
Drug
Intervention Name(s)
Busulfan
Intervention Description
Busulfan 82.1 mg*hr/L IV on days -5 to -2 or days -8 to -5
Intervention Type
Drug
Intervention Name(s)
Melphalan
Intervention Description
Melphalan 50 mg/m2 IV on days -4 to -2
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
200 mg/m2 intravenous given once on day-1
Intervention Type
Drug
Intervention Name(s)
Levetiracetam
Other Intervention Name(s)
Keppra
Intervention Description
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.
Primary Outcome Measure Information:
Title
Determine the rate of GVHD after alpha beta TCR depletion
Description
GVHD incidence after treatment.
Time Frame
85 months
Secondary Outcome Measure Information:
Title
Transplant engraftment
Description
Monitor median rate of engraftment by 42 days.
Time Frame
42 days
Title
Graft Failure
Description
Determine the rate of graft failure by day 100 (defined as lack of achievement of an ANC >=500/mL with associated pancytopenia)
Time Frame
100 days
Title
Non-relapse mortality (NRM)
Description
Determine the incidence of non-relapse mortality (NRM) at 100 days and 1 year
Time Frame
12 months
Title
Overall survival (OS)
Description
Number of participants experiencing progression free survival at one year follow up
Time Frame
12 months
10. Eligibility
Sex
All
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Margaret MacMillan
Phone
612-626-2961
Email
macmi002@umn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Margaret MacMillan
Organizational Affiliation
University of Minnesota Masonic Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Minnesota Masonic Cancer Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Margaret MacMillan
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
For the purposes of data and safety monitoring, this study is classified as high risk (investigator initiated under an IND). Therefore the following requirements will be fulfilled:
The Masonic Cancer Center Data and Safety Monitoring Council (DSMC) will review the study's progress at least quarterly.
The PI will comply with at least twice yearly monitoring of the project by the Masonic Cancer Center monitoring services.
The PI will oversee the submission of all reportable adverse events per the definition of reportable in Section 11.5 to the Masonic Cancer Center's SAE Coordinator, the University of Minnesota IRB, and the FDA.
Learn more about this trial
MT2021-08T Cell Receptor Alpha/Beta Depletion PBSC Transplantation for Heme Malignancies
We'll reach out to this number within 24 hrs