Autologous Cytomegalovirus (CMV)-Specific Cytotoxic T Cells for Cytomegalovirus (CMV) Reactivation
Condition: Leukemia; Lymphoma
MeSH terms: Cytomegalovirus Infections
Intervention: Cytomegalovirus (CMV)-Specific Cytotoxic T Cells (CTLs)
Intervention description: CTL product given as single infusion within 72 hours of CMV reactivation. CTL dose infused will be at a maximum dose of 10e5 viable CD3+ T cells/kg.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Leukemia; Lymphoma; Blood And Marrow Transplantation; Hematological malignancies; Cytotoxic T cells; CTL; Cytomegalovirus; CMV; Allogeneic hematopoietic stem cell transplantation; HSCT

Summary:

      The goal of this clinical research study is to learn if giving cytotoxic T lymphocytes (CTLs)
      can help control CMV when it reactivates (becomes active again) in patients who receive an
      allogeneic stem cell transplant. Researchers also want to learn about the safety of giving
      CTLs to patients who have had a stem cell transplant.
    

Eligibility criteria:

        Inclusion Criteria:

          1. STEP 1: Within 30 days of study entry: Patients with a history of bone marrow
             disorders including hematological malignancies and aplastic anemia, Myelodysplastic
             Syndrome (MDS) and Myeloproliferative disorder (MPD) planning to undergo allogeneic
             HSCT with reduced intensity or myeloablative conditioning regimens.

          2. Disease status must be complete remission by standard criteria for Lymphoma and Acute
             Leukemia patients.

          3. Patients with Myelodysplastic Syndrome (MDS) and Myeloproliferative Disorder (MPD)
             must have <5% blasts in the bone marrow.

          4. Patients with T Cell ALL must be in complete remission and MRD negative (-) by flow
             cytometry and molecular studies.

          5. Patients >/= 18 years of age.

          6. Karnofsky greater than or equal to 80%.

          7. CMV seropositive.

          8. Donor is either matched related, matched unrelated, mismatched unrelated, or
             haploidentical. Cord blood recipients are also eligible.

          9. Hgb greater than 10 g/L.

         10. Patient or patient's legal representative, parent(s) or guardian able to provide
             written informed consent.

         11. Negative pregnancy test in female patients of childbearing potential.

         12. STEP 2: Eligibility at time of generating and infusing CMV-specific cytotoxic T cells
             (adoptive immunotherapy): CMV reactivation defined as CMV DNAemia >/= 137 copies/ml.

         13. Evidence of neutrophil engraftment defined as the absolute neutrophil count (ANC)> 0.5
             X 10^3/for 3 consecutive days.

         14. Clinical status to allow tapering of steroids to less than 0.5 mg/kg/day prednisone or
             equivalent.

         15. Negative pregnancy test in female patients of childbearing potential.

        Exclusion Criteria:

          1. STEP 1: Within 30 days of study entry: T cell leukemia or lymphoma.

          2. CMV seronegative.

          3. Positive for HIV, HBV, HCV, HTLV1 and/or HTLV2.

          4. STEP 2: Eligibility at time of generating and infusing CMV-specific cytotoxic T cells
             (adoptive immunotherapy): Documented CMV end-organ disease.

          5. Patients receiving ATG, or Campath within 28 days of CMV reactivation.

          6. Patients with other uncontrolled infections. For bacterial infections, patients must
             be receiving definitive therapy and have no signs of progressing infection for 72
             hours prior to generating CTLs. For fungal infections patients must be receiving
             definitive systemic anti-fungal therapy and have no signs of progressing infection for
             1 week prior to generating CTLs. Progressing infection is defined as hemodynamic
             instability attributable to sepsis or new symptoms, worsening physical signs or
             radiographic findings attributable to infection. Persisting fever without other signs
             or symptoms will not be interpreted as progressing infection.

          7. Patients who have received donor lymphocyte infusion (DLI) within 28 days.

          8. Patients with active acute GVHD grades II-IV.

          9. Active and uncontrolled relapse of malignancy.