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Clinical Trial of Expanded and Activated Autologous NK Cells to Treat Multiple Myeloma (NK-VS-MM)

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ClinicalTrials.gov Identifier: NCT02481934
Recruitment Status : Completed
First Posted : June 25, 2015
Results First Posted : December 5, 2016
Last Update Posted : April 17, 2017
Sponsor:
Collaborator:
Hospital Infantil Universitario Niño Jesús, Madrid, Spain
Information provided by (Responsible Party):
Joaquín Martínez López, MD, PhD, Hospital Universitario 12 de Octubre

Tracking Information
First Submitted Date  ICMJE June 10, 2015
First Posted Date  ICMJE June 25, 2015
Results First Submitted Date  ICMJE July 20, 2016
Results First Posted Date  ICMJE December 5, 2016
Last Update Posted Date April 17, 2017
Study Start Date  ICMJE March 2013
Actual Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 11, 2016)
Number of Participants With Adverse Events During NKAE Treatment [ Time Frame: 16 months ]
Toxicity will be assessed by adverse events count during NKAE treatment monitoring peripheral blood absolute neutrophil count (cells/μl). Toxicity will be evaluated monthly during NKAE treatment (4 months). During follow-up, it will be assessed monthly the first 6 months. After that, quarterly until one year of follow-up, based on Common Toxicity Criteria for Adverse Events of the National Cancer Institute (CTCAE) to v.4.03.
Original Primary Outcome Measures  ICMJE
 (submitted: June 23, 2015)
Hematologic toxicity during NKAE treatment [ Time Frame: 16 months ]
Toxicity will be assessed monitoring peripheral blood absolute neutrophil count (cells/μl). Toxicity will be evaluated monthly during NKAE treatment (4 months). During follow-up, it will be assessed monthly the first 6 months. After that, quarterly until one year of follow-up, based on Common Toxicity Criteria for Adverse Events of the National Cancer Institute (CTCAE) to v.4.03.
Change History Complete list of historical versions of study NCT02481934 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 11, 2016)
Number of Participants With Peripheral Blood Monoclonal Protein Reduction or Stabilization [ Time Frame: 16 months ]
Efficacy will be assessed monthly during NKAE treatment (4 months) by peripheral blood monoclonal protein monitoring. During follow-up, efficacy will be evaluated monthly the first 6 months. After that, quarterly until one year of follow-up.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 23, 2015)
Peripheral blood monoclonal protein reduction [ Time Frame: 16 months ]
Efficacy will be assessed monthly during NKAE treatment (4 months). During follow-up, efficacy will be evaluated monthly the first 6 months. After that, quarterly until one year of follow-up.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clinical Trial of Expanded and Activated Autologous NK Cells to Treat Multiple Myeloma
Official Title  ICMJE Phase 1 Clinical Trial to Evaluate Security and Dose of Expanded and Activated Autologous NK Cells Infusions in Consolidation of Multiple Myeloma Patients Treatment on Second or Later Relapse.
Brief Summary The purpose of this study is to determine wether activated and expanded autologous Natural Killer cells (NKAEs) are effective in the treatment of patients with multiple myeloma on second or later relapse. NKAEs are used in combination with anti-myeloma drugs such as lenalidomide or bortezomib.
Detailed Description

It is expected to enroll 10 to 15 patients within 18 months. Patients have to achieve stable disease after induction therapy. Peripheral blood from patients will be collected every cycle (n=4) to produce NKAEs under Good Manufacturing Practice (GMP) conditions peripheral blood mononuclear cell (PBMCs) will be co-cultured with a genetically modified cell line (K562-mb15-41BBL) and 100 IU/ml interleukin-2.

Treatment consists of 4 cycles of anti-myeloma consolidation treatment with two infusions of NKAEs every day 1 and 8 of each cycle. Usually, chosen treatment regime will be bortezomib (Velcade) or lenalidomide (Revlimid). These treatments are used to be combined with corticosteroid medications which needs to be suspended before NKAEs infusions. A washout period of 2 weeks is required.

NKAEs dose of cells will be constant, 7.5x106/kg. There will be an interim analysis intra-cohort one week after the first batch of two infusions. If at the analysis no grade IV adverse effect is observed we will proceed to the second cycle and the inclusion of other patients.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Procedure: NKAE cells infusion
    Expanded and activated autologous NK cells infusion. Each patient will receive two infusions of 7.5 x 106 expanded and activated autologous NK cells/kg/cycle.
    Other Names:
    • NKAE infusion
    • Activated and expanded autologous NK cells infusion
  • Drug: Lenalidomide
    Lenalidomide, 10 mg oral/day during 21 days (cycle). Patients will receive 4 cycles.
    Other Name: Revlimid
  • Drug: Bortezomib
    Bortezomib, 1.3 mg/m2, s.c., days 1, 4, 8 and 11/cycle. Patients will receive 4 cycles.
    Other Name: Velcade
Study Arms  ICMJE Experimental: NKAE cells infusion + chemotherapy
Expanded and activated autologous NK cells (NKAEs) + chemotherapy (lenalidomide OR bortezomib).
Interventions:
  • Procedure: NKAE cells infusion
  • Drug: Lenalidomide
  • Drug: Bortezomib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 23, 2015)
5
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE October 2016
Actual Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects between 20 and 80 years old
  • With multiple myeloma in 2nd or later relapse or showing resistance after 2 treatment lines
  • Eastern Cooperative Oncology Group (ECOG) ≤ 2
  • Life expectancy greater than six months
  • Creatinine clearance rate more than 30 ml / min
  • Subjects who have received at least 4 cycles of rescue treatment under the procedures of the 12 de Octubre Hospital (rescue treatment will vary depending on previous anti-myeloma treatment). After treatment, patients must have shown chemosensitivity and disease stabilization.
  • Will be included subjects with partial response or stable disease (for at least 2 cycles) after 75% of planned rescue treatment or patients at subclinical progression (defined as an increase of monoclonal component ≥ 25%) at any time of rescue treatment. Subjects have to show tolerance to rescue treatment, without G3/4 adverse effects, if G1/2 adverse effects exist they must be analyzed immediately before starting reinfusion program.
  • Subjects have to agree to participate in the trial and they have to sign informed consent.

Exclusion Criteria:

  • Subjects with clinical progression or complete response will not be included.
  • Any of the following abnormal laboratory results:

Absolute Neutrophil Count < 1000/ µL Platelets Count < 50000/ µL in those patients with bone marrow infiltration lower than 50% Measured creatinine clearance <30 ml/min Hemoglobin level ≤ 8 g/dL Peripheral neuropathy ≥ Grade 2

  • Subjects have received allogeneic stem cell transplant.
  • Subjects with heart disease which compromises patient's life or protocol accomplishment.
  • Subjects with past clinical history of malignant disease within 3 years (exceptions are squamous or basal cell carcinoma).
  • Subjects receiving another investigational drug or having received investigational drug within 30 days before screening.
  • Subjects who require chronic steroid or immunosuppressive treatment.
  • Any condition, including abnormally laboratory results, that might compromise the patient´s life if he participate in this study.
  • Any concurrent medical condition, abnormally laboratory results or any psychological disorder that prevent the patient to sign the informed consent.
  • Pregnant or fertile women.
  • Patients known to be seropositive for human immunodeficiency virus (VIH) or having active hepatitis A, B or C.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02481934
Other Study ID Numbers  ICMJE NK-VS-MM
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Joaquín Martínez López, MD, PhD, Hospital Universitario 12 de Octubre
Study Sponsor  ICMJE Joaquín Martínez López, MD, PhD
Collaborators  ICMJE Hospital Infantil Universitario Niño Jesús, Madrid, Spain
Investigators  ICMJE
Principal Investigator: Joaquín Martínez López, M.D, Ph.D Hospital Universitario 12 de Octubre
PRS Account Hospital Universitario 12 de Octubre
Verification Date March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP