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

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ClinicalTrials.gov Identifier: NCT01392989
Recruitment Status : Completed
First Posted : July 13, 2011
Results First Posted : May 7, 2019
Last Update Posted : May 7, 2019
Sponsor:
Information provided by (Responsible Party):
Everett Meyer, Stanford University

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.

Condition or disease Intervention/treatment Phase
Neural Tube Defects Anemia Leukemia, Myeloid Bone Marrow Transplant Failure Myelodysplastic Syndromes (MDS) Myeloproliferative Disorders Drug: CIK cells Drug: Cyclosporine Drug: Mycophenolate Mofetil Drug: Thymoglobulin Radiation: Total Lymphoid Irradiation (TLI) Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Post Transplant Infusion of Allogeneic Cytokine Induced Killer Cells as Consolidative Therapy After Non-Myeloablative Allogeneic Transplantation in Patients With Myelodysplasia or Myeloproliferative Disorders
Study Start Date : March 2011
Actual Primary Completion Date : June 7, 2016
Actual Study Completion Date : March 19, 2017


Arm Intervention/treatment
Experimental: 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.
Drug: CIK cells
Standard of care
Other Name: Cytokine-induced Killer Cells

Drug: Cyclosporine
5 mg/kg, po
Other Names:
  • cyclosporin
  • cyclosporin A

Drug: Mycophenolate Mofetil
15 mg/kg, oral
Other Names:
  • MMF
  • CellCept

Drug: Thymoglobulin
7.5 mg/kg, IV
Other Names:
  • Anti-thymocyte globulin
  • ATG

Radiation: Total Lymphoid Irradiation (TLI)



Primary Outcome Measures :
  1. Full Donor Chimerism (FDC) [ Time Frame: 90 days ]
    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.


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: 2 years ]
    Overall survival (OS) is an expression of the number of participants that remain alive 2 years after cytokine-induced killer (CIK) infusion. The outcome will be reported as the number of participants alive 2 years after CIK infusion, a number without dispersion.

  2. Event-free Survival (EFS) Rate [ Time Frame: 2 years ]
    Event-free Survival (EFS) rate will be assessed on all enrolled participants and is defined as the duration of time after cytokine-induced killer (CIK) cell infusion that the participants remain alive with experiencing relapse, Grade 3 to 4 acute graft vs host disease (aGVHD), or death. The outcome will be reported as the number of participants, stratified by receipt of CIK cells, that did not experience a specified event, a number without dispersion.

  3. Number of Participants That Experience Grade 2 to 4 aGvHD Within 100 Days and 1 Year [ Time Frame: 1 year ]

    Acute graft vs host disease (aGvHD) Grade 2 to 4 was staged & graded using modified Keystone criteria, as below. The outcome is reported as the number of participants that experience Grade 2 to 4 aGvHD within 100 days and 1 year.

    • Stage 1: Skin: rash < 25% of skin. Liver: bilirubin 2 to 3 mg/dL. Gut: diarrhea 500 to 1000 mL/day or persistent nausea with positive biopsy for GvHD
    • Stage 2: Skin: rash 25 to 50% of skin. Liver: bilirubin 3 to 6 mg/dL. Gut: diarrhea 1000 to 1500 mL/day.
    • Stage 3: Skin: rash > 50% of skin. Liver: bilirubin 6 to 15 mg/dL. Gut: diarrhea > 1500 mL/day.
    • Stage 4: Skin: generalized erythroderma with bulla formation. Liver: bilirubin > 15 mg/dL. Gut: severe abdominal pain with or without ileus Grade of aGvHD was determined as follows.
    • Grade 1: Stage 1-2 Skin + No Liver stage + No Gut stage
    • Grade 2: Stage 3 Skin OR Stage 1 Liver or Stage 1 Gut
    • Grade 3: No Skin stage + Stage 2 to 3 Liver Stage 2 to 4 Gut
    • Grade 4: Stage 4 Skin + or Stage 2

  4. Pre-transplant Expression of Natural-killer Group 2, Member D (NKG2D) Ligands [ Time Frame: Pre-transplant ]
    Pre-transplant expression of natural-killer group 2, member D (NKG2D) ligands MIC A, MIC B, and the UL16 binding proteins (ULBPs) will be assessed in participants' bone marrow aspirates. The outcomes is expressed as the number of participants whose expression level for each ligand was elevated compared to background, represented by the known levels for individual without cancer.



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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01392989


Locations
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United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Everett Meyer
Investigators
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Principal Investigator: Everett Meyer, MD, PhD Stanford University

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Everett Meyer, Assistant Professor-Med, Stanford University
ClinicalTrials.gov Identifier: NCT01392989     History of Changes
Other Study ID Numbers: IRB-18127
SU-04202010-5724 ( Other Identifier: Stanford University )
BMT217 ( Other Identifier: OnCore )
First Posted: July 13, 2011    Key Record Dates
Results First Posted: May 7, 2019
Last Update Posted: May 7, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Preleukemia
Leukemia, Myeloid
Neural Tube Defects
Spinal Dysraphism
Myelodysplastic Syndromes
Myeloproliferative Disorders
Syndrome
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Leukemia
Neoplasms by Histologic Type
Nervous System Malformations
Nervous System Diseases
Congenital Abnormalities
Cyclosporine
Mycophenolic Acid
Cyclosporins
Thymoglobulin
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents