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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05794880
• Other study ID #: IIT-MOSKOP-MABD
• Status: Recruiting
• Phase: N/A
• Start date: May 1, 2023
• Est. completion date: May 2032

Study information

• Verified date: June 2023
• Source: Medical College of Wisconsin
• Contact: Meredith Beversdorf, RN
• Phone: 414-266-5891
• Email: mbeversdorf[@]childrenswi.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: May 2032
• Est. primary completion date: May 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 25 Years

Eligibility

Inclusion Criteria:

1. Patient age < 25 years. Both genders and all races eligible.

2. 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)

3. Karnofsky Performance Status = 60% for patients 16 years and older and Lansky Play Score = 60 for patients under 16 years of age (Appendix 1)

4. Evaluation of organ status as per MCW BMT SOP

5. 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.

6. Signed consent by parent/guardian or able to give consent if =18 years.

7. Negative pregnancy test for patients capable of childbearing potential

8. 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:

1. Unrelated donor meets National Marrow Donor Program criteria for donation

2. Infectious disease testing

3. MCW BMT procedures apply for determining donor eligibility, including donor screening and testing for relevant communicable disease agents and diseases.

4. 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.

5. 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

6. Haploidentical Related Donor:

1. 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:

1. Patients who do not meet disease, organ, or infectious criteria.

2. No suitable donor

3. Pregnant or lactating patients are ineligible as many of the medications used in this protocol could be harmful to unborn children and infants

4. 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.

5. Participating in a concomitant Phase 1 or 2 study involving treatment of disease

6. 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.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia in Remission
• Acute Myeloid Leukemia in Remission
• Biphenotypic Acute Leukemia
• Burkitt Leukemia
• Burkitt Lymphoma
• Chronic Myelogenous Leukemia - Chronic Phase
• Chronic Myelogenous Leukemia With Crisis of Blast Cells
• Chronic Myelogenous Leukemia, Accelerated Phase
• Hematologic Diseases
• Leukemia
• Leukemia, Biphenotypic, Acute
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Chronic-Phase
• Lymphoblastic Lymphoma
• Lymphoma
• Myelodysplasia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Device:
• Magnetic-Activated Cell Sorter (CliniMACS, Miltenyi)
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.

Locations

Country	Name	City	State
United States	Children's Wisconsin	Milwaukee	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Medical College of Wisconsin

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Assess tempo of CD4+ T cell reconstitution.		2 years
Other	Assess tempo of immune reconstitution.		2 years
Other	Assess ATG exposure using pre- and post- HCT AUC estimates using ATG dosing module		1 year
Primary	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		1 year
Secondary	Evaluate incidence of chronic GVHD		5 years
Secondary	Evaluate time to platelet engraftment		1 years
Secondary	Assess incidence of viral infections		2 years
Secondary	Evaluate incidence of relapse/progressive disease		2 years
Secondary	Evaluate incidence of treatment-related mortality (TRM).		2 years
Secondary	Evaluate overall and relapse free survival (RFS) at 1 year		1 years