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

NCT01392989 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: IRB-18127SU-04202010-5724BMT217
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Full Donor Chimerism (FDC)

  Proportion of patients achieving full donor T-cell chimerism (FDC) by on or before Day 90 post non-myeloablative allogeneic transplant with allogeneic cytokine-induced killer (CIK) cells will be determined. FDC is defined as the attainment of \>95% donor type CD3+ cells. The outcome will be reported as number of participants who achieved full donor chimerism, a number without dispersion.

  90 days

Secondary Outcomes (4)

• Overall Survival (OS)

  2 years

• Event-free Survival (EFS) Rate

  2 years

• Number of Participants That Experience Grade 2 to 4 aGvHD Within 100 Days and 1 Year

  1 year

• Pre-transplant Expression of Natural-killer Group 2, Member D (NKG2D) Ligands

  Pre-transplant

Study Arms (1)

Allogeneic Cytokine-induced Killer Cells (CIK)

EXPERIMENTAL

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

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

Interventions

CIK cells DRUG

Standard of care

Also known as: Cytokine-induced Killer Cells

Allogeneic Cytokine-induced Killer Cells (CIK)

Cyclosporine DRUG

5 mg/kg, po

Also known as: cyclosporin, cyclosporin A

Allogeneic Cytokine-induced Killer Cells (CIK)

Mycophenolate Mofetil DRUG

15 mg/kg, oral

Also known as: MMF, CellCept

Allogeneic Cytokine-induced Killer Cells (CIK)

Thymoglobulin DRUG

7.5 mg/kg, IV

Also known as: Anti-thymocyte globulin, ATG

Allogeneic Cytokine-induced Killer Cells (CIK)

Total Lymphoid Irradiation (TLI) RADIATION

Allogeneic Cytokine-induced Killer Cells (CIK)

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Everett Meyer: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (1)

• 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.

  PMID: 30951840 DERIVED

MeSH Terms

Conditions

Neural Tube Defects; Anemia; Leukemia, Myeloid; Myelodysplastic Syndromes; Myeloproliferative Disorders

Interventions

Cyclosporine; Mycophenolic Acid; thymoglobulin; Antilymphocyte Serum

Condition Hierarchy (Ancestors)

Nervous System Malformations; Nervous System Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Everett Meyer, Assistant Professor of Medicine (Blood and Marrow Transplantation)
• Organization: Stanford University

evmeyer@stanford.edu

650) 725-5816

Study Officials

• Everett Meyer, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor-Med

Study Record Dates

• First Submitted: June 21, 2011
• First Posted: July 13, 2011
• Study Start: March 1, 2011
• Primary Completion: June 7, 2016
• Study Completion: March 19, 2017
• Last Updated: May 7, 2019
• Results First Posted: May 7, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)