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

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ClinicalTrials.gov Identifier: NCT01795573
Recruitment Status : Recruiting
First Posted : February 20, 2013
Last Update Posted : August 6, 2019
Sponsor:
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

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
Graft Versus Host Disease Biological: Cultured Treg cells 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Phase I Trial of Ex-vivo Expanded Donor Regulatory T Cells for Prevention of Acute Graft-Versus-Host Disease
Actual Study Start Date : June 24, 2014
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
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).




Primary Outcome Measures :
  1. Maximally Tolerated dose (MTD) [ Time Frame: 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 :
  1. Acute GVHD incidence [ Time Frame: 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.

  2. Relapse Free Survival [ Time Frame: 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.

  3. Non-relapse Mortality [ Time Frame: Up to 1 year ]
    Defined as mortality while underlying malignancy is in remission.

  4. Overall Survival (OS) [ Time Frame: 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.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01795573


Contacts
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Contact: Joseph Pidala, MD, PhD 813-745-2556 joseph.pidala@moffitt.org

Locations
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United States, Florida
H Lee Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Joseph Pidala, MD, PhD    813-745-2556    joseph.pidala@moffitt.org   
Contact: Michelle Burton    813-745-1537    michelle.burton@moffitt.org   
Sub-Investigator: Melissa Alsina, MD         
Sub-Investigator: Ernesto Ayala, MD         
Sub-Investigator: Lia Perez, MD         
Sub-Investigator: Jose Leonel Ochoa-Bayona, MD         
Sub-Investigator: Brian Betts, MD         
Sub-Investigator: Fred Locke, MD         
Sub-Investigator: Farhad Khimani, MD         
Sub-Investigator: Taiga Nishihori, MD         
Sub-Investigator: Mohamed Kharfan-Dabaja, MD         
Sub-Investigator: Asmita Mishra, MD         
Sub-Investigator: Linda Kelley, PhD         
Principal Investigator: Joseph Pidala, MD         
Principal Investigator: Claudio Anasetti, MD         
Sub-Investigator: Michael Nieder, MD         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Investigators
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Principal Investigator: Joseph Pidala, MD, PhD Moffitt Cancer Center

Additional Information:
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Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT01795573     History of Changes
Other Study ID Numbers: MCC-17263
First Posted: February 20, 2013    Key Record Dates
Last Update Posted: August 6, 2019
Last Verified: August 2019
Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
GVHD
AML
ALL
MDS
CLL
NHL
HL
MM
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases