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

NCT01795573 | Completed Phase 1 DMC

• 1 other identifier: MCC-17263
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Graft Versus Host Disease

Keywords

GVHD; AML; ALL; MDS; CLL; NHL; HL; MM

Outcome Measures

Primary Outcomes (1)

• Maximally Tolerated dose (MTD)

  MTD of donor Treg in combination with standard dose SIR/TAC immune suppression. The occurrence of dose-limiting toxicity in \>= 33% serves as the boundary for the MTD of donor Treg.

  Up to 1 year

Secondary Outcomes (4)

• Acute GVHD incidence

  Up to day 100

• Relapse Free Survival

  Up to 1 year

• Non-relapse Mortality

  Up to 1 year

• Overall Survival (OS)

  Up to 1 year

Study Arms (1)

Cultured Treg cells

OTHER

Co-culturing of recipient dendritic cells and donor Treg cells given prior to allogeneic stem cell transplant

Biological: Cultured Treg cells

Interventions

Cultured Treg cells BIOLOGICAL

Co-culturing of recipient dendritic cells and donor Treg. Treg administration will occur 2 days before the allogeneic stem cell transplant (i.e. day -2 with reference of day 0 as stem cell infusion date).

Cultured Treg cells

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Antithymocyte globulin (ATG) as part of the conditioning regimen

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (1)

H Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Related Links

• H. Lee Moffitt Cancer Center \& Research Institute

MeSH Terms

Conditions

Graft vs Host Disease

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Joseph Pidala, MD, PhD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2013
• First Posted: February 20, 2013
• Study Start: October 29, 2014
• Primary Completion: August 14, 2020
• Study Completion: August 14, 2020
• Last Updated: November 3, 2022

Record last verified: 2022-11

Locations

US (1)