Ex-vivo Expanded Donor Regulatory T Cells for Prevention of Acute Graft-Versus-Host Disease
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Detailed 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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Other: Cultured Treg cells Co-culturing of recipient dendritic cells and donor Treg cells given prior to allogeneic stem cell transplant |
Biological: Cultured Treg cells
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).
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Outcome Measures
Primary Outcome Measures
- Maximally Tolerated dose (MTD) [Up to 1 year]
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.
Secondary Outcome Measures
- Acute GVHD incidence [Up to day 100]
Clinical evidence of acute GVHD will be recorded per standard grading scheme. GVHD grade will be reported weekly from day 0-100 both for site-specific involvement, as well as an overall composite score.
- Relapse Free Survival [Up to 1 year]
Defined as time from transplantation (day 0 as day of stem cell infusion per standard nomenclature) to relapse or death from any cause.
- Non-relapse Mortality [Up to 1 year]
Defined as mortality while underlying malignancy is in remission.
- Overall Survival (OS) [Up to 1 year]
Defined as time from transplantation (day 0 as day of stem cell infusion per standard nomenclature) to death from any cause.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Signed informed consent
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Diagnoses:
- 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.
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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
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MDS: Bone marrow with ≤5 percent myeloblasts with normal maturation of all cell lines; Peripheral blood demonstrates hemoglobin ≥11 g/dL, platelets ≥100 x 109/L, neutrophils ≥1 x 109/L, and no circulating blasts
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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
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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
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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
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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
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MDS: May have achieved CR through either hypomethylating agent therapy, induction chemotherapy, or other therapy
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MDS: Low/intermediate-1 IPSS risk category patients are eligible only if they have failed prior therapy or are transfusion-dependent
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Peripheral blood white blood count (WBC) greater than 2,000 per microliter (required for collection of dendritic cell precursors)
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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
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Infectious disease criteria:
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No active infection; infection controlled with antimicrobial therapy is not excluded
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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]
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Hepatitis B and C negative by serology or RT-PCR
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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
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Performance status: Karnofsky Performance Status Score ≥ 60%.
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Agreement to utilize effective contraceptive methods during the study (for one year)
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Eligible donors will include siblings age ≥ 18 matched with the recipient at HLA-A, B, C, and DRB1
Exclusion Criteria:
- Antithymocyte globulin (ATG) as part of the conditioning regimen
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | H Lee Moffitt Cancer Center | Tampa | Florida | United States | 33612 |
Sponsors and Collaborators
- H. Lee Moffitt Cancer Center and Research Institute
Investigators
- Principal Investigator: Joseph Pidala, MD, PhD, Moffitt Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- MCC-17263