Clinical trial NCT01795573: Ex-vivo Expanded Donor Regulatory T Cells for Prevention of Acute Graft-Versus-Host Disease
Official title: Phase I Trial of Ex-vivo Expanded Donor Regulatory T Cells for Prevention of Acute Graft-Versus-Host Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Graft Versus Host Disease
Keywords: GVHD
AML
ALL
MDS
CLL
NHL
HL
MM
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
First posted: 2013-02-20
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

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.

Eligibility 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

Primary outcomes:
measure: Maximally Tolerated dose (MTD)
timeFrame: Up to 1 year
Secondary outcomes:
measure: Acute GVHD incidence
timeFrame: Up to day 100
measure: Relapse Free Survival
timeFrame: Up to 1 year
measure: Non-relapse Mortality
timeFrame: Up to 1 year
measure: Overall Survival (OS)
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center
state: Florida
Study officials:
affiliation: Moffitt Cancer Center
name: Joseph Pidala, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: