Clinical Trial 17263

Cancer Type: Malignant Hematology
Interventions:FK506 (Tacrolimus); Rapamune (Sirolimus); Rapamycin (Sirolimus); Sirolimus; Tacrolimus

Study Type: Prevention
Phase of Study: Phase I
Investigators:

  • Joseph Pidala

Overview

Study Title

Phase I Trial of ex-vivo Expanded Donor Regulatory T Cells for Prevention of Acute Graft-Versus-Host Disease

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.

Objective

The primary objective of this trial is 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. Secondary objectives will monitor Treg repopulation, longevity, and antigen-specific suppressive function after HCT in vivo.

Inclusion Criteria

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  • Age 18 to 17 years
  • 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.
  • AML, ALL: Absolute neutrophil count (ANC) (>1000/microL) and platelet count (>100,000/microL); Absence of extramedullary leukemia; Less than 5 % blast cells present in the bone marrow
  • MDS: Bone marrow with ≤5 % 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; ANC >1500/microL; Platelet count >100,000/microL; No clonal lymphocytes in the peripheral blood by immunophenotyping; Bone marrow with no evidence of clonal CLL
  • 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 % 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 WBC greater than 2,000 per microliter (required for collection of dendritic cell precursors)
  • Adequate vital organ function: LVEF ≥ 45% by MUGA scan or echocardiogram; FEV1, FVC, and DLCO ≥ 50% of predicted values on pulmonary function tests; Transaminases (AST, ALT) > Infectious disease criteria: No active infection; infection controlled with antimicrobial therapy is not excluded
  • 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

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  • 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. DLCO will not be included in assessment of pulmonary risk, excepting those with DLCO > Antithymocyte globulin (ATG) as part of the conditioning regimen