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Phase I Trial of Ex-vivo Expanded Donor Regulatory T Cells for Prevention of Acute Graft-versus-host Disease


Phase 1
18 Years
70 Years
Open (Enrolling)
Both
Graft Versus Host Disease

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Trial Information

Phase I Trial of Ex-vivo Expanded Donor Regulatory T Cells for Prevention of Acute Graft-versus-host Disease


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


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) i. complete remission is defined per morphologic,
cytogenetic, FISH, molecular, and radiographic imaging studies appropriate for each
condition listed

1. 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 2. 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 3. 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 4. 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

5. 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 6. 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 FLC ratio
in addition to the above criteria ii. MDS - may have achieved CR through either
hypomethylating agent therapy, induction chemotherapy, or other therapy iii. MDS -
low/intermediate-1 IPSS risk category patients are eligible only if they have failed
prior therapy or are transfusion-dependent

- Peripheral blood WBC greater than 2,000 per microliter (required for collection of
dendritic cell precursors)

- Adequate vital organ function:

LVEF ≥ 45% by MUGA scan FEV1, FVC, and 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:

a. No active infection; infection controlled with antimicrobial therapy is not
excluded b. HIV negative by ELISA or RT-PCR [if ELISA is positive and RT-PCR is
negative, the ELISA is considered false positive] c. Hepatitis B and C negative by
serology or RT-PCR d. Must complete full screening panel: i. HIV 1, 2 serology and
RT-PCR ii. HTLV 1,2 serology iii. RPR serology iv. EBV serology v. CMV serology vi.
HSV serology vii.VZV serology

- Performance status: Karnofsky Performance Status Score ≥ 60%.

- Agreement to utilize effective contraceptive methods during the study (for one year)

Exclusion Criteria:

- Those with any Sorror's co-morbidity factors with score > 3

- 2 or more Sorror's factors with composite score of ≥ 3

- Important modification to co-morbidity index calculation

a. DLCO will not be included in assessment of pulmonary risk, excepting those with
DLCO < 50%, who will merit a score of 3 and thereby be excluded from the trial.

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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Outcome Measure:

acute GVHD incidence

Outcome Description:

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

Outcome Time Frame:

100 days

Safety Issue:

No

Principal Investigator

Joseph Pidala, MD, MS

Investigator Role:

Principal Investigator

Investigator Affiliation:

Moffitt Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

MCC 17263

NCT ID:

NCT01795573

Start Date:

February 2013

Completion Date:

December 2015

Related Keywords:

  • Graft Versus Host Disease
  • GVHD
  • AML
  • ALL
  • MDS
  • CLL
  • NHL
  • HL
  • MM
  • Graft vs Host Disease

Name

Location

H Lee Moffitt Cancer CenterTampa, Florida  33612