Post T-plant Infusion of Allogeneic Cytokine Induced Killer (CIK) Cells as Consolidative Therapy in Myelodysplastic Syndromes/Myeloproliferative Disorders
Condition: Neural Tube Defects; Anemia; Leukemia, Myeloid; Bone Marrow Transplant Failure; Myelodysplastic Syndromes (MDS); Myeloproliferative Disorders
MeSH terms: Preleukemia; Leukemia, Myeloid; Neural Tube Defects; Spinal Dysraphism; Myelodysplastic Syndromes; Myeloproliferative Disorders; Syndrome
Intervention: CIK cells; Cyclosporine; Mycophenolate Mofetil; Thymoglobulin; Total Lymphoid Irradiation (TLI)
Intervention description: Standard of care; 5 mg/kg, po; 15 mg/kg, oral; 7.5 mg/kg, IV
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Cyclosporins; Thymoglobulin; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 44.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No

Summary:

      Allogeneic stem cell transplantation (transplant of blood cells from another individual) is a
      treatment option for patients with myelodysplasia or myeloproliferative Disorders. During the
      course of this study, it will be evaluated whether a particular type of blood cell, called a
      cytokine-induced killer (CIK) cell, may add benefit to allogeneic stem cell transplantation.
      CIK cells are present in small quantities in the bloodstream but their numbers can be
      expanded after a brief period of nurturing in a laboratory.
    

Eligibility criteria:

        INCLUSION CRITERIA, RECIPIENT WITH MYELODYSPLASTIC SYNDROME (MDS)

          -  Diagnosis of MDS classifiable by the World Health Organization (WHO) on the basis of:

               -  Refractory anemia

               -  Refractory anemia with excess blasts-1

               -  Refractory anemia with excess blasts-2

               -  Refractory cytopenia with multi-lineage dysplasia

               -  Refractory cytopenia with multi-lineage dysplasia and ringed sideroblasts

               -  Chronic myelomonocytic leukemia (CMML)

               -  MDS transformed to acute leukemia

               -  MDS-unclassified

          -  Participants with advanced MDS must have < 10% marrow blasts prior to receiving
             conditioning with TLI/ATG, documented by marrow examination within 1 month prior.

          -  Participants with evolution to acute leukemia (AML) must be in a morphologic leukemia
             free-state (MLFS) with blasts < 5%

        INCLUSION CRITERIA, RECIPIENT WITH MYELOPROLIFERATIVE DISORDER (MPD)

          -  Diagnosis of MPD on the basis of:

               -  Idiopathic myelofibrosis

               -  Polycythemia vera

               -  Essential thrombocythemia

               -  Chronic myelomonocytic leukemia (CML)

               -  CML, Philadelphia chromosome-negative

               -  Chronic neutrophilic leukemia

               -  Chronic eosinophilic leukemia

               -  Hypereosinophilic cyndrome

               -  Systemic mastocytosis

          -  < 10% marrow blasts prior to receiving conditioning with TLI/ATG, documented by marrow
             examination within 1 month prior.

          -  Participants with evolution to acute leukemia (AML) must be in a morphologic leukemia
             free-state (MLFS) with blasts < 5%. Presence of residual dysplastic features following
             cytoreductive therapy is acceptable.

        INCLUSION CRITERIA, RECIPIENT WITH THERAPY-RELATED MYELOID NEOPLASM (t MDS)

          -  < 10% marrow blasts prior to receiving conditioning with TLI/ATG, documented by marrow
             examination within 1 month prior.

          -  Morphologic leukemia free-state with blasts < 5 %.

          -  Age > 50 years, or < 50 years of age but at high-risk for regimen-related toxicity
             associated with conventional myeloablative transplants due to pre-existing medical
             conditions or prior therapy

          -  Availability of a fully HLA-matched or single antigen/allele mismatched sibling or
             unrelated donor

          -  Prior malignancy diagnosed > 5 years ago without evidence of disease, or < 5 years ago
             with life expectancy of > 5 years are eligible (prior malignancy is not a requirement)

        INCLUSION CRITERIA, DONOR

          -  Donors must be HLA-matched or one allele mismatched.

          -  Donor age < 75 (EXCEPTION by Principal Investigator discretion)

          -  Must consent to PBSC mobilization with G-CSF; apheresis; and collection and donation
             of plasma

          -  Donor must consent to placement of a central venous catheter in the event that
             peripheral venous access is limited.

        EXCLUSION CRITERIA, RECIPIENT

        Any of the following:

          -  Uncontrolled CNS involvement with disease

          -  Pregnant

          -  Cardiac function: ejection fraction (EF) < 35% or uncontrolled cardiac failure

          -  Diffusing capacity of the lungs for carbon monoxide (DLCO) < 40% predicted

          -  Bilirubin > 3 mg/dL

          -  Aspartate aminotransferase (AST) > 3x the upper limit of normal (ULN)

          -  Alanine aminotransferase (ALT) > 3x ULN

          -  Estimated creatinine clearance < 50 mL/min

          -  Karnofsky performance score (KPS) < 70%

          -  Documented fungal disease that is progressive despite treatment

          -  HIV-positive

        EXCLUSION CRITERIA, DONOR

        Any of the following:

          -  Identical twin to recipient

          -  Pregnant or lactating

          -  Prior malignancy within the preceding 5 years (EXCEPTION: non-melanoma skin cancers)

          -  HIV seropositivity