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CompletedNCT02481934NK-VS-MMUpdated Aug 20, 2021Results posted

Clinical Trial of Expanded and Activated Autologous NK Cells to Treat Multiple Myeloma

A Phase 1 interventional study of NKAE cells infusion and Lenalidomide in Multiple Myeloma, sponsored by Joaquín Martínez López, MD, PhD. Completed at 1 site in Spain. Open to participants aged 20 Years to 80 Years. Per ClinicalTrials.gov, last updated 2021-08-20.

Sponsored by Joaquín Martínez López, MD, PhD · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
5
Allocation
Not applicable
Ages
20 Years to 80 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Multiple Myeloma

Keywords

  • Recurrent multiple myeloma
  • NK cells
  • cell therapy
  • NKAE
  • Relapsed multiple myeloma
03

In context

Multiple Myeloma

3,632 studies on the registry are indexed under Multiple Myeloma; 745 are open to participants now.

This study's enrollment of 5 is below the median of 41 across 2,907 interventional studies indexed under Multiple Myeloma.

Browse Multiple Myeloma studies →

Lead sponsor

This is the only study on the registry with Joaquín Martínez López, MD, PhD as lead sponsor.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
20 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
5 participants (actual)

Study arms

  • Experimental
    NKAE cells infusion + chemotherapy

    Expanded and activated autologous NK cells (NKAEs) + chemotherapy (lenalidomide OR bortezomib).

    Procedure: NKAE cells infusion · Drug: Lenalidomide · Drug: Bortezomib

Interventions

  • ProcedureNKAE 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.

    Also known as: NKAE infusion, Activated and expanded autologous NK cells infusion

  • DrugLenalidomide

    Lenalidomide, 10 mg oral/day during 21 days (cycle). Patients will receive 4 cycles.

    Also known as: Revlimid

  • DrugBortezomib

    Bortezomib, 1.3 mg/m2, s.c., days 1, 4, 8 and 11/cycle. Patients will receive 4 cycles.

    Also known as: Velcade

06

What researchers measure

Primary outcomes

  1. Number of Participants With Adverse Events During NKAE Treatment

    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.

    Time frame: 16 months

Secondary outcomes

  1. Number of Participants With Peripheral Blood Monoclonal Protein Reduction or Stabilization

    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.

    Time frame: 16 months

07

Results

Posted Dec 5, 2016
Limitations and caveats
Volume of the peripheral blood from patients was limiting in order to perform different cohorts with more NKAE cells infusions.

Participant flow

Recruitment was performed between march 2013 and october 2014 at Hospital 12 de Octubre in Madrid.

Participant flow — Overall Study
MilestoneNKAE Cells Infusion + Chemotherapy
Started5
Completed3
Not completed2
Withdrew: Death2

Outcome measures

PrimaryNumber of Participants With Adverse Events During NKAE Treatment

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.

Time frame:
16 months
Reported as:
Number · participants
Number of Participants With Adverse Events During NKAE Treatment
participantsNKAE Cells Infusion + Chemotherapy
Number of Participants With Adverse Events During NKAE Treatment2
SecondaryNumber of Participants With Peripheral Blood Monoclonal Protein Reduction or Stabilization

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.

Time frame:
16 months
Reported as:
Number · participants
Number of Participants With Peripheral Blood Monoclonal Protein Reduction or Stabilization
participantsNKAE Cells Infusion + Chemotherapy
Number of Participants With Peripheral Blood Monoclonal Protein Reduction or Stabilization5

Adverse events

Collected over 4 months during treatment with NKAE cells.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
NKAE Cells Infusion + Chemotherapy—2/5 (40%)2/5 (40%)
Most frequent serious events
Most frequent serious events
EventNKAE Cells Infusion + Chemotherapy
Gastrointestinal bleedingGastrointestinal disorders1/5
Vertebral compressionMusculoskeletal and connective tissue disorders1/5
Most frequent other events
Most frequent other events
EventNKAE Cells Infusion + Chemotherapy
NeutropeniaImmune system disorders2/5

Baseline characteristics

The number of participants was directly related with the cost of expanded and activated NK cells production.

Age, Continuous
Age, Continuous(years)NKAE Cells Infusion + Chemotherapy
Median62 (61 to 72)
Sex: Female, Male
Sex: Female, Male(Participants)NKAE Cells Infusion + Chemotherapy
Female3
Male2
Region of Enrollment
Region of Enrollment(participants)NKAE Cells Infusion + Chemotherapy
Spain5
08

Study locations

1 site
  • Hospital Universitario 12 de Octubre
    Madrid, 28041, Spain
09

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 20, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02481934
Lead sponsor
Joaquín Martínez López, MD, PhD
Collaborators
Hospital Infantil Universitario Niño Jesús, Madrid, Spain
Responsible party
Joaquín Martínez López, MD, PhD (Hematology Head of department, M.D., Ph.D., Hospital Universitario 12 de Octubre) — Sponsor-investigator
First posted
Jun 25, 2015
Start date
Mar 2013
Primary completion
Jul 2016
Completion
Oct 2016
Results posted
Dec 5, 2016
Last update
Aug 20, 2021

Study contacts

Joaquín Martínez López, M.D, Ph.D
principal investigator · Hospital Universitario 12 de Octubre

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Aug 2021. You cannot join it, but the record below documents what was studied.

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