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

NCT ID: NCT01392989

Last Updated: 2019-05-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2017-03-19

Brief 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.

Detailed 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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Allogeneic Cytokine-induced Killer Cells (CIK)

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

Group Type: EXPERIMENTAL

CIK cells

Intervention Type: DRUG

Standard of care

Cyclosporine

Intervention Type: DRUG

5 mg/kg, po

Mycophenolate Mofetil

Intervention Type: DRUG

15 mg/kg, oral

Thymoglobulin

Intervention Type: DRUG

7.5 mg/kg, IV

Total Lymphoid Irradiation (TLI)

Intervention Type: RADIATION

Interventions

CIK cells

Standard of care

Intervention Type: DRUG

Cyclosporine

5 mg/kg, po

Intervention Type: DRUG

Mycophenolate Mofetil

15 mg/kg, oral

Intervention Type: DRUG

Thymoglobulin

7.5 mg/kg, IV

Intervention Type: DRUG

Total Lymphoid Irradiation (TLI)

Intervention Type: RADIATION

Other Intervention Names

Cytokine-induced Killer Cells; cyclosporin; cyclosporin A; MMF; CellCept; Anti-thymocyte globulin; ATG

Eligibility Criteria

Inclusion Criteria

• 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%

• 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.

• < 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)

• 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

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

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

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Everett Meyer

OTHER

Sponsor Role: lead

Responsible Party

Everett Meyer

Assistant Professor-Med

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Everett Meyer, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University School of Medicine

Stanford, California, United States

Countries

United States

References

Narayan R, Benjamin JE, Shah O, Tian L, Tate K, Armstrong R, Xie BJ, Lowsky R, Laport G, Negrin RS, Meyer EH. Donor-Derived Cytokine-Induced Killer Cell Infusion as Consolidation after Nonmyeloablative Allogeneic Transplantation for Myeloid Neoplasms. Biol Blood Marrow Transplant. 2019 Jul;25(7):1293-1303. doi: 10.1016/j.bbmt.2019.03.027. Epub 2019 Apr 3.

Reference Type: DERIVED

PMID: 30951840 (View on PubMed)

Other Identifiers

SU-04202010-5724

Identifier Type: OTHER

Identifier Source: secondary_id

BMT217

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-18127

Identifier Type: -

Identifier Source: org_study_id