Allogeneic CD6 Chimeric Antigen Receptor T Regulatory Cells (CD6-CAR Tregs) for the Treatment of Patients With Chronic Graft Versus Host Disease After Allogeneic Hematopoietic Cell Transplantation

PRIMARY OBJECTIVES: I. Determine if CD6-CAR Tregs administration is safe and tolerable in patients who developed chronic graft-versus-host disease (cGVHD), by evaluation of toxicities, including: type, frequency, severity, attribution, time course and duration. II. To evaluate the feasibility to produce donor derived CD6-CAR Tregs. SECONDARY OBJECTIVES: I. Obtain preliminary evidence of CD6-CAR Tregs activity against cGVHD by estimating the response rate (as defined by 2014 National Institute of Health \[NIH\] consensus development project on clinical trials in cGVHD). II. Evaluate changes in cGVHD severity using physician -reported cGVHD activity assessment form. III. Evaluate changes in symptom activity using cGVHD activity assessment patient self-report. IV. Evaluate failure-free survival (FFS). V. Quantify CD6-CAR Treg cells in peripheral blood. VI. Characterize and assess changes in immune biomarkers over time in blood samples. EXPLORATORY OBJECTIVES: I. Percent and counts from peripheral blood T cell subsets in hematopoietic stem/progenitor cell compartments to assess ability of CD6-CAR Tregs to suppress pathogenic T cell activity and proliferation. II. Profile cytokine levels over time and changes to assess the ability of CD6-CAR Tregs to down-regulate proinflammatory cytokine production (IFNgamma, IL-6, TNFalpha) and adhesion molecules that promote pathogenic T cell. III. For subjects who receive tafasitamab-cxix for CAR Treg ablation, describe the activity of infusional tafasitamab-cxix to eliminate transferred CD6 CAR Treg cells. OUTLINE: This is a dose-escalation study of CD6-CAR Treg cells followed by a dose-expansion study. Donors undergo leukapheresis over 2-4 hours for collection of peripheral blood mononuclear cells (PBMSc) and the manufacturing of CD6-CAR Treg cells over 2 weeks. Patients then receive CD6-CAR Treg intravenously on day 0. Patients may also receive ablation tafasitamab IV post Treg cell infusion on days 1, 4, 8, 15, 22 for 1 cycle. If ablation is not complete by day 28, patients may receive an additional 1-2 cycles per investigator's discretion. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography (ECHO), computed tomography (CT), and x-ray imaging during screening and as clinically indicated. Patients undergo blood specimen collection on study and during follow-up. Patients may undergo a biopsy on study as well as a lumbar puncture and magnetic resonance imaging (MRI)/CT as clinically indicated on study. After completion of study treatment, patients are followed up to 28 days, monthly for 1 year, and then yearly for 15 years.