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

August 19, 2021 updated by: Joaquín Martínez López, MD, PhD

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.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

5

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NKAE cells infusion + chemotherapy
Expanded and activated autologous NK cells (NKAEs) + chemotherapy (lenalidomide OR bortezomib).
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 Names:
  • Revlimid
Drug: Bortezomib
Bortezomib, 1.3 mg/m2, s.c., days 1, 4, 8 and 11/cycle. Patients will receive 4 cycles.
Other Names:
  • Velcade

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
16 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
16 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Joaquín Martínez López, MD, PhD

Collaborators

Hospital Infantil Universitario Niño Jesús, Madrid, Spain

Investigators

  • Principal Investigator: Joaquín Martínez López, M.D, Ph.D, Hospital Universitario 12 de Octubre

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2013

Primary Completion (Actual)

July 1, 2016

Study Completion (Actual)

October 1, 2016

Study Registration Dates

First Submitted

June 10, 2015

First Submitted That Met QC Criteria

June 23, 2015

First Posted (Estimate)

June 25, 2015

Study Record Updates

Last Update Posted (Actual)

August 20, 2021

Last Update Submitted That Met QC Criteria

August 19, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NK-VS-MM

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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