Ex-vivo Expanded Donor Regulatory T Cells for Prevention of Acute Graft-Versus-Host Disease

H. Lee Moffitt Cancer Center and Research Institute

Status and phase

Completed

Phase 1

Conditions

Graft Versus Host Disease

Treatments

Biological: Cultured Treg cells

Study type

Interventional

Funder types

Other

Identifiers

NCT01795573

MCC-17263

Details and patient eligibility

About

Clinical trial of allospecific regulatory t cells (Tregs) for prevention of acute graft-versus-host disease (GVHD) in human leukocyte antigen (HLA) identical sibling transplants.

Full description

To evaluate the safety of sirolimus based immune suppression and ex-vivo expanded donor regulatory T cells for the prevention of acute graft-versus-host disease following allogeneic hematopoietic cell transplantation.

Enrollment

38 patients

Sex

All

Ages

18 to 70 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Signed informed consent
Diagnoses:

a. Hematologic malignancies - Acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS), chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), multiple myeloma (MM) - in complete remission (CR). Complete remission is defined per morphologic, cytogenetic, FISH, molecular, and radiographic imaging studies appropriate for each condition listed.
- AML, ALL: Normal values for absolute neutrophil count (>1000/microL) and platelet count (>100,000/microL); Absence of extramedullary leukemia; Less than 5 percent blast cells present in the bone marrow
- MDS: Bone marrow with ≤5 percent myeloblasts with normal maturation of all cell lines; Peripheral blood demonstrates hemoglobin ≥11 g/dL, platelets ≥100 x 10^9/L, neutrophils ≥1 x 10^9/L, and no circulating blasts
- CLL: Absence of constitutional symptoms attributable to CLL; No lymph nodes >1.5 cm in diameter on computed tomography; No hepatomegaly or splenomegaly by computed tomography; Absolute neutrophil count >1500/microL; Platelet count >100,000/microL; No clonal lymphocytes in the peripheral blood by immunophenotyping; Bone marrow with no evidence of clonal CLL (by flow cytometry and/or immunohistochemistry
- NHL: No clinical evidence of disease or disease-related symptoms; Typically FDG-avid lymphomas: a post-treatment residual mass of any size is permitted as long as it is PET negative; Variably FDG-avid lymphoma/FDG avidity unknown: all lymph nodes normal size by CT; Spleen and liver non-palpable and without nodules; If pretreatment bone marrow biopsy was positive, repeat bone marrow biopsy must be negative; if morphologically indeterminate, immunohistochemistry should be negative If pretreatment bone marrow biopsy was positive, repeat bone marrow biopsy must be negative; if morphologically indeterminate, immunohistochemistry should be negative
- HL: No clinical evidence of disease or disease-related symptoms; A post-treatment residual mass of any size is permitted as long as it is PET negative; Spleen and liver must be non-palpable and without nodules; If a pre-treatment bone marrow biopsy was positive, an adequate bone marrow biopsy from the same site must be cleared of infiltrate; if this is indeterminate by morphology, immunohistochemistry should be negative
- MM: Absence of monoclonal protein in serum and urine by immunofixation with no current evidence of soft tissue plasmacytoma; Bone marrow aspirate and biopsy must demonstrate less than 5 percent clonal plasma cells; In patients who lack measurable M proteins in the serum and urine being monitored using the FLC levels, the definition of CR requires a normalization of the free light chain (FLC) ratio in addition to the above criteria
- MDS: May have achieved CR through either hypomethylating agent therapy, induction chemotherapy, or other therapy
- MDS: Low/intermediate-1 IPSS risk category patients are eligible only if they have failed prior therapy or are transfusion-dependent
Peripheral blood white blood count (WBC) greater than 2,000 per microliter (required for collection of dendritic cell precursors)
Adequate vital organ function: Left ventricular ejection fraction (LVEF) ≥ 45% by multigated acquisition (MUGA) scan or echocardiogram; Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and diffusing lung capacity oxygenation (DLCO) ≥ 50% of predicted values on pulmonary function tests; Transaminases (AST, ALT) < 3 times upper limit of normal values; Creatinine clearance ≥ 50cc/min
Infectious disease criteria:
- No active infection; infection controlled with antimicrobial therapy is not excluded
- HIV negative by ELISA or reverse transcription polymerase chain reaction (RT-PCR) [if ELISA is positive and RT-PCR is negative, the ELISA is considered false positive]
- Hepatitis B and C negative by serology or RT-PCR
- Must complete full screening panel: HIV 1, 2 serology and RT-PCR; human T cell lymphotropic virus types 1/2 (HTLV-1/2) serology; rapid plasma reagin (RPR) serology; Epstein-Barr virus (EBV) serology; Cytomegalovirus (CMV) serology; herpes simplex virus (HSV) serology; Varicella-. Zoster Virus (VZV) serology
Performance status: Karnofsky Performance Status Score ≥ 60%.
Agreement to utilize effective contraceptive methods during the study (for one year)
Eligible donors will include siblings age ≥ 18 matched with the recipient at HLA-A, B, C, and DRB1