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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Stanford University
Sponsor:
Information provided by (Responsible Party):
Everett Meyer, Stanford University
ClinicalTrials.gov Identifier:
NCT01392989
First received: June 21, 2011
Last updated: July 10, 2014
Last verified: July 2014
  Purpose

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, we will attempt to learn 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 Intervention 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
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • proportion of patients achieving full donor T cell chimerism by Day 90 post non-myeloablative allogeneic transplant with allogeneic CIK cells [ Time Frame: 90 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • OS (Overall survival); incidence of acute Graft versus host disease following CIK infusion [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • EFS (Event Free Survival); incidence of acute Graft versus host disease following CIK infusion [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 21
Study Start Date: March 2011
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Allogeneic Cytokine Induced Killer Cells
Target dose of ≥ 5 x 106 CD34+ cells/kg of recipient body weight plus an additional 2 x109 mononuclear cells.
Drug: CIK cells
Standard of care
Other Name: Cytokine-induced Killer Cells
Drug: Cyclosporine
5 mg/kg, po
Other Names:
  • cyclosporine
  • 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

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

4.1.1 Recipient Inclusion Criteria to start ATG/TLI:

Diagnosis Myelodysplastic Syndrome Criteria

(A) Diagnosis of MDS classifiable by the WHO system as

  • Refractory Anemia
  • Refractory Cytopenia with Multilineage Dysplasia
  • MDS-unclassified
  • Refractory Cytopenias with Multilineage Dysplasia and Ringed Sideroblasts, Refractory Anemia with Excess Blasts-1
  • Refractory Anemia with Excess Blasts-2
  • Chronic myelomonocytic leukemia (CMML)
  • MDS transformed to acute leukemia.

Patients with advanced MDS must have < 10% marrow blasts prior to receiving conditioning with TLI/ATG. Less than 10% marrow blasts must be documented by marrow examination within 1 month of starting conditioning. If necessary, a cytoreductive regimen will be determined by referring centers.

Patients with evolution to AML are required to be in a morphologic leukemia free-state with blasts <5% (50).

Myeloproliferative Disorders

B) Myeloproliferative disorders to be included:

  • Idiopathic Myelofibrosis
  • Polycythemia vera
  • Essential Thrombocythemia
  • Chronic Myelomonocytic Leukemia
  • Chronic Neutrophilic Leukemia
  • Chronic Eosinophilic Leukemia
  • Philadelphia chromosome-negative CML.
  • Hypereosinophilic Syndrome
  • Systemic Mastocytosis

Patients with MPD must have < 10% marrow blasts prior to receiving conditioning with TLI/ATG. Less than 10% marrow blasts must be documented by marrow examination within 1 month of starting conditioning. If necessary, a cytoreductive regimen will be determined by referring centers.

Patients with evolution to AML are required to be in a morphologic leukemia-free state less than 5% in a marrow aspirate. Presence of residual dysplastic features following cytoreductive therapy is acceptable.

Therapy-related myeloid neoplasms

Patients with t-MDS must have < 10% marrow blasts prior to receiving conditioning with TLI/ATG. Less than 10% marrow blasts must be documented by marrow examination within 1 month of starting conditioning. If necessary, a cytoreductive regimen will be determined by referring centers.

Patients with t-AML are required to be in a morphologic leukemia free-state with blasts <5%.

2. Patient age > 50 years, or for patients <50 years of age but because of pre-existing medical conditions or prior therapy are considered to be at high risk for regimen-related toxicity associated with conventional myeloablative transplants.

3. A fully HLA matched or single antigen/allele mismatched sibling or unrelated donor is available.

4.2 Donor Eligibility

4.2.1 Inclusion Criteria - Related Donors

  1. Donors must be HLA-matched or one allele mismatched.
  2. Donor age < 75 unless cleared by the Principal Investigator
  3. Donor must consent to peripheral blood stem cells (PBSC) mobilization with G-CSF and apheresis
  4. Donor must consent to placement of a central venous catheter in the event that peripheral venous access is limited.

Exclusion Criteria:

4.1.2 Recipient Exclusion Criteria

  1. Uncontrolled CNS involvement with disease
  2. Females who are pregnant
  3. Organ dysfunction defined as follows:

    • Cardiac function: ejection fraction (EF) <35% or uncontrolled cardiac failure
    • Pulmonary: DLCO <40% predicted
    • Liver function abnormalities: elevation of bilirubin to > 3 mg/dl and/or AST or ALT >3x the upper limit of normal
    • Estimated creatinine clearance < 50 ml/min
  4. Karnofsky performance score (KPS) < 70% (Appendix F)
  5. Documented fungal disease that is progressive despite treatment
  6. Viral infections: HIV positive patients are not eligible for this protocol. Hepatitis B and C positive patients will be evaluated on a case-by-case basis
  7. Patients with prior malignancies diagnosed > 5 years ago without evidence of disease are eligible. Patients with a prior malignancy treated < 5 years ago but have a life expectancy of > 5 years for that malignancy are eligible.

4.1.3 Recipient Exclusion Criteria to proceed to CIK infusion 1. Uncontrolled infection 2. Evidence of disease relapse 3. Grade 2 or above GVHD (Grade 1 GVHD to be evaluated by Principal Investigator) 4. Does not meet release criteria for CIK cells

.2.2 Exclusion Criteria - Related Donor

  1. Identical twin
  2. Pregnant or lactating females
  3. Prior malignancy within the preceding five years, with the exception of non-melanoma skin cancers.
  4. HIV seropositivity

4.2.3 Unrelated Donor Inclusion Criteria

  1. Donors must be HLA-matched or one allele or antigen mismatched.
  2. Donor must consent to PBSC mobilization with G-CSF and apheresis as well as collection and donation of plasma. Bone marrow unrelated donors are not eligible for this protocol.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01392989

Locations
United States, California
Stanford University School of Medicine Recruiting
Stanford, California, United States, 94305
Contact: Physician Referrals    650-723-0822      
Contact: Cancer Clinical Trials Office    (650) 498-7061      
Principal Investigator: Everett Meyer         
Sub-Investigator: Sally Arai         
Sub-Investigator: Dr. Janice (Wes) Brown         
Sub-Investigator: Laura Johnston         
Sub-Investigator: Ginna Laport         
Sub-Investigator: Robert Lowsky         
Sub-Investigator: David Miklos         
Sub-Investigator: Robert S Negrin         
Sub-Investigator: Judith Anne Shizuru         
Sub-Investigator: Samuel Md Strober         
Sub-Investigator: Kenneth Weinberg         
Sub-Investigator: Wen-Kai Weng         
Sponsors and Collaborators
Everett Meyer
Investigators
Principal Investigator: Everett Meyer Stanford University
  More Information

No publications provided

Responsible Party: Everett Meyer, Assistant Professor-Med, Stanford University
ClinicalTrials.gov Identifier: NCT01392989     History of Changes
Other Study ID Numbers: BMT217, SU-04202010-5724, 18127
Study First Received: June 21, 2011
Last Updated: July 10, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Myeloproliferative Disorders
Anemia
Leukemia
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neural Tube Defects
Spinal Dysraphism
Hematologic Diseases
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Precancerous Conditions
Nervous System Malformations
Nervous System Diseases
Congenital Abnormalities
Antilymphocyte Serum
Cyclosporins
Cyclosporine
Mycophenolate mofetil
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014