- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01795573
Ex-vivo Expanded Donor Regulatory T Cells for Prevention of Acute Graft-Versus-Host Disease
Phase I Trial of Ex-vivo Expanded Donor Regulatory T Cells for Prevention of Acute Graft-Versus-Host Disease
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Florida
-
Tampa, Florida, United States, 33612
- H Lee Moffitt Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: PREVENTION
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Cultured Treg cells
Co-culturing of recipient dendritic cells and donor Treg cells given prior to allogeneic stem cell transplant
|
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).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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Up to 1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Acute GVHD incidence
Time Frame: Up to day 100
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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.
|
Up to day 100
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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.
|
Up to 1 year
|
Non-relapse Mortality
Time Frame: Up to 1 year
|
Defined as mortality while underlying malignancy is in remission.
|
Up to 1 year
|
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.
|
Up to 1 year
|
Collaborators and Investigators
Investigators
- Principal Investigator: Joseph Pidala, MD, PhD, Moffitt Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- MCC-17263
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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