Post T-plant Infusion of Allogeneic Cytokine Induced Killer (CIK) Cells as Consolidative Therapy in Myelodysplastic Syndromes/Myeloproliferative Disorders

Everett Meyer

Status and phase: Completed; Phase 2

Conditions: Anemia; Neural Tube Defects; Myeloproliferative Disorders; Bone Marrow Transplant Failure; Myelodysplastic Syndromes (MDS); Leukemia, Myeloid

Treatments: Drug: Cyclosporine; Drug: Thymoglobulin; Radiation: Total Lymphoid Irradiation (TLI); Drug: Mycophenolate Mofetil; Drug: CIK cells

Study type: Interventional

Funder types: Other

Identifiers

NCT01392989

IRB-18127

BMT217 (Other Identifier)

SU-04202010-5724 (Other Identifier)

Details and patient eligibility

About

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.

Full description

Primary Objectives:

To determine the rate of conversion to FDC following infusion of allogeneic CIK cells among patients with MDS, therapy-related myeloid neoplasms, or MPD who receive non myeloablative preparative regimen of TLI / ATG followed by allogeneic HCT and consolidation with allogeneic CIK cells.

Secondary Objectives:

• To determine the 2 year overall survival (OS) and event free survival (EFS)
• To determine the incidence of acute GVHD following infusion of allogeneic CIK cells
• To assess the pre-transplant expression of NKG2D ligands in patients' bone marrow aspirates.

Enrollment: 44 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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44 participants in 1 patient group

Allogeneic Cytokine-induced Killer Cells (CIK)

Experimental group

Description:

Target dose of ≥ 5 x 10e6 CD34+ cells/kg of recipient body weight plus an additional 2 x10e9 mononuclear cells.

Treatment:

Radiation: Total Lymphoid Irradiation (TLI)

Drug: Mycophenolate Mofetil

Drug: CIK cells

Drug: Thymoglobulin

Drug: Cyclosporine