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MCW Alpha/Beta T-Cell and B-Cell Depletion With Targeted ATG Dosing

Primary Purpose

Leukemia, Acute Myeloid Leukemia in Remission, Myelodysplasia

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Magnetic-Activated Cell Sorter (CliniMACS, Miltenyi)
Sponsored by
Medical College of Wisconsin
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia

Eligibility Criteria

0 Years - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patient age < 25 years. Both genders and all races eligible. Disease eligibility Acute myeloid leukemia, primary or secondary - Disease status: MRD negative (flow MRD ≤ 0.1%) Myelodysplasia Acute lymphoblastic leukemia - Disease status: MRD negative Chronic myelogenous leukemia - Disease status: chronic phase, accelerated phase or blast crisis now in second chronic phase Mixed lineage or biphenotypic acute leukemia- Disease status: MRD negative Lymphoblastic lymphoma - Disease status: in remission Burkitt's lymphoma/leukemia - Disease status: in remission Lymphoma after relapse - Disease status: in remission Other malignant hematologic diseases in remission (to be approved by PI) Karnofsky Performance Status ≥ 60% for patients 16 years and older and Lansky Play Score ≥ 60 for patients under 16 years of age (Appendix 1) Evaluation of organ status as per MCW BMT SOP Infectious disease criteria: No active untreated infection. Patients with possible fungal infections must have had at least 2 weeks of appropriate anti-fungal antibiotics and be asymptomatic. Signed consent by parent/guardian or able to give consent if ≥18 years. Negative pregnancy test for patients capable of childbearing potential Sexually active patients capable of child-bearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment. Sexually active men must agree to use barrier contraceptive for the duration of treatment. Donor Eligibility: Unrelated donor meets National Marrow Donor Program criteria for donation Infectious disease testing MCW BMT procedures apply for determining donor eligibility, including donor screening and testing for relevant communicable disease agents and diseases. Only Peripheral blood stem cells will be used for stem cell source on this study therefore donor must be willing to undergo G-CSF mobilization and stem cell apheresis. Donor matching. High resolution typing at all loci to be performed. Unrelated Donor: a. HLA typing of at least 10 alleles is required. Donor must be matched at 9/10 or 10/10 alleles (HLA A, B, C, DRB1, DQB1).Donor and collection center willing to undergo mobilization and apheresis Haploidentical Related Donor: Haploidentical parent or other related donor: Minimum match level full haploidentical (at least 5/10; HLA A, B, C, DRB1, DQB1 alleles), but use of haploidentical donors with extra matches (e.g. 6, 7, or 8/10) encouraged. Exclusion Criteria: Patients who do not meet disease, organ, or infectious criteria. No suitable donor Pregnant or lactating patients are ineligible as many of the medications used in this protocol could be harmful to unborn children and infants Receiving concomitant chemotherapy, radiation therapy; immunotherapy or other anti-cancer therapy for treatment of disease other than is specified in the protocol. Maintenance or other post-HCT therapy can be considered after discussion with the study PI. Participating in a concomitant Phase 1 or 2 study involving treatment of disease Active malignancy other than eligible disease specified in the protocol. Patients with prior malignancy can be eligible as long as at least 1 year post treatment for that malignancy.

Sites / Locations

  • Children's WisconsinRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Alpha/Beta T cell depletion (TCD) plus CD19+ depletion

Arm Description

Alpha beta T cell and B cell depleted allogeneic transplantation with individualized dosing of ATG for patients with hematologic malignancies

Outcomes

Primary Outcome Measures

Evaluate incidence and extent of aGVHD and engraftment in patients receiving alpha/beta T cell depleted and CD19+ B cell depleted stem cell transplant with individualized ALC-based dosing of ATG

Secondary Outcome Measures

Evaluate incidence of chronic GVHD
Evaluate time to platelet engraftment
Assess incidence of viral infections
Evaluate incidence of relapse/progressive disease
Evaluate incidence of treatment-related mortality (TRM).
Evaluate overall and relapse free survival (RFS) at 1 year

Full Information

First Posted
March 8, 2023
Last Updated
June 9, 2023
Sponsor
Medical College of Wisconsin
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1. Study Identification

Unique Protocol Identification Number
NCT05794880
Brief Title
MCW Alpha/Beta T-Cell and B-Cell Depletion With Targeted ATG Dosing
Official Title
Matched Unrelated Donor and Partially Matched Related Donor Peripheral Stem Cell Transplantation With Alpha/Beta T-Cell and B-Cell Depletion for Patients With Hematologic Malignancies With Targeted ATG Dosing Pilot Study, IDE 13641
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2023 (Actual)
Primary Completion Date
May 2027 (Anticipated)
Study Completion Date
May 2032 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical College of Wisconsin

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a single arm pilot study for patients with hematologic malignancies receiving unrelated or haploidentical related mobilized peripheral stem cells (PSCs) using the CliniMACS system for alpha/beta T cell depletion plus CD19+ B cell depletion with individualized ALC-based dosing of ATG to study impact on engraftment, GVHD, and disease free survival

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Acute Myeloid Leukemia in Remission, Myelodysplasia, Acute Lymphoblastic Leukemia in Remission, Chronic Myelogenous Leukemia - Chronic Phase, Chronic Myelogenous Leukemia, Accelerated Phase, Chronic Myelogenous Leukemia With Crisis of Blast Cells, Biphenotypic Acute Leukemia, Lymphoblastic Lymphoma, Burkitt Lymphoma, Burkitt Leukemia, Lymphoma After Relapse, Other Malignant Hematologic Diseases in Remission

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Alpha/Beta T cell depletion (TCD) plus CD19+ depletion
Arm Type
Experimental
Arm Description
Alpha beta T cell and B cell depleted allogeneic transplantation with individualized dosing of ATG for patients with hematologic malignancies
Intervention Type
Device
Intervention Name(s)
Magnetic-Activated Cell Sorter (CliniMACS, Miltenyi)
Intervention Description
Participants in this study will receive a blood stem cell transplant, which will use an investigational device called the CliniMACs device to remove alpha/beta T cells and B cells from the blood cells collected from the donor. This is called T cell depletion and B cell depletion.
Primary Outcome Measure Information:
Title
Evaluate incidence and extent of aGVHD and engraftment in patients receiving alpha/beta T cell depleted and CD19+ B cell depleted stem cell transplant with individualized ALC-based dosing of ATG
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Evaluate incidence of chronic GVHD
Time Frame
5 years
Title
Evaluate time to platelet engraftment
Time Frame
1 years
Title
Assess incidence of viral infections
Time Frame
2 years
Title
Evaluate incidence of relapse/progressive disease
Time Frame
2 years
Title
Evaluate incidence of treatment-related mortality (TRM).
Time Frame
2 years
Title
Evaluate overall and relapse free survival (RFS) at 1 year
Time Frame
1 years
Other Pre-specified Outcome Measures:
Title
Assess tempo of CD4+ T cell reconstitution.
Time Frame
2 years
Title
Assess tempo of immune reconstitution.
Time Frame
2 years
Title
Assess ATG exposure using pre- and post- HCT AUC estimates using ATG dosing module
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
0 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient age < 25 years. Both genders and all races eligible. Disease eligibility Acute myeloid leukemia, primary or secondary - Disease status: MRD negative (flow MRD ≤ 0.1%) Myelodysplasia Acute lymphoblastic leukemia - Disease status: MRD negative Chronic myelogenous leukemia - Disease status: chronic phase, accelerated phase or blast crisis now in second chronic phase Mixed lineage or biphenotypic acute leukemia- Disease status: MRD negative Lymphoblastic lymphoma - Disease status: in remission Burkitt's lymphoma/leukemia - Disease status: in remission Lymphoma after relapse - Disease status: in remission Other malignant hematologic diseases in remission (to be approved by PI) Karnofsky Performance Status ≥ 60% for patients 16 years and older and Lansky Play Score ≥ 60 for patients under 16 years of age (Appendix 1) Evaluation of organ status as per MCW BMT SOP Infectious disease criteria: No active untreated infection. Patients with possible fungal infections must have had at least 2 weeks of appropriate anti-fungal antibiotics and be asymptomatic. Signed consent by parent/guardian or able to give consent if ≥18 years. Negative pregnancy test for patients capable of childbearing potential Sexually active patients capable of child-bearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment. Sexually active men must agree to use barrier contraceptive for the duration of treatment. Donor Eligibility: Unrelated donor meets National Marrow Donor Program criteria for donation Infectious disease testing MCW BMT procedures apply for determining donor eligibility, including donor screening and testing for relevant communicable disease agents and diseases. Only Peripheral blood stem cells will be used for stem cell source on this study therefore donor must be willing to undergo G-CSF mobilization and stem cell apheresis. Donor matching. High resolution typing at all loci to be performed. Unrelated Donor: a. HLA typing of at least 10 alleles is required. Donor must be matched at 9/10 or 10/10 alleles (HLA A, B, C, DRB1, DQB1).Donor and collection center willing to undergo mobilization and apheresis Haploidentical Related Donor: Haploidentical parent or other related donor: Minimum match level full haploidentical (at least 5/10; HLA A, B, C, DRB1, DQB1 alleles), but use of haploidentical donors with extra matches (e.g. 6, 7, or 8/10) encouraged. Exclusion Criteria: Patients who do not meet disease, organ, or infectious criteria. No suitable donor Pregnant or lactating patients are ineligible as many of the medications used in this protocol could be harmful to unborn children and infants Receiving concomitant chemotherapy, radiation therapy; immunotherapy or other anti-cancer therapy for treatment of disease other than is specified in the protocol. Maintenance or other post-HCT therapy can be considered after discussion with the study PI. Participating in a concomitant Phase 1 or 2 study involving treatment of disease Active malignancy other than eligible disease specified in the protocol. Patients with prior malignancy can be eligible as long as at least 1 year post treatment for that malignancy.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Meredith Beversdorf, RN
Phone
414-266-5891
Email
mbeversdorf@childrenswi.org
Facility Information:
Facility Name
Children's Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Meredith Beversdorf, RN
Phone
414-266-5891
Email
mbeversdorf@childrenswi.org
First Name & Middle Initial & Last Name & Degree
Amy Moskop

12. IPD Sharing Statement

Plan to Share IPD
No

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MCW Alpha/Beta T-Cell and B-Cell Depletion With Targeted ATG Dosing

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