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

Primary Purpose

Multiple Myeloma

Status
Completed
Phase
Phase 1
Locations
Spain
Study Type
Interventional
Intervention
NKAE cells infusion
Lenalidomide
Bortezomib
Sponsored by
Joaquín Martínez López, MD, PhD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Recurrent multiple myeloma, NK cells, cell therapy, NKAE, Relapsed multiple myeloma

Eligibility Criteria

20 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Hospital Universitario 12 de Octubre

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

NKAE cells infusion + chemotherapy

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
June 10, 2015
Last Updated
August 19, 2021
Sponsor
Joaquín Martínez López, MD, PhD
Collaborators
Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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1. Study Identification

Unique Protocol Identification Number
NCT02481934
Brief Title
Clinical Trial of Expanded and Activated Autologous NK Cells to Treat Multiple Myeloma
Acronym
NK-VS-MM
Official Title
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.
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
March 2013 (undefined)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
October 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Joaquín Martínez López, MD, PhD
Collaborators
Hospital Infantil Universitario Niño Jesús, Madrid, Spain

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Recurrent multiple myeloma, NK cells, cell therapy, NKAE, Relapsed multiple myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
NKAE cells infusion + chemotherapy
Arm Type
Experimental
Arm Description
Expanded and activated autologous NK cells (NKAEs) + chemotherapy (lenalidomide OR bortezomib).
Intervention Type
Procedure
Intervention Name(s)
NKAE cells infusion
Other Intervention Name(s)
NKAE infusion, Activated and expanded autologous NK cells infusion
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
Revlimid
Intervention Description
Lenalidomide, 10 mg oral/day during 21 days (cycle). Patients will receive 4 cycles.
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Other Intervention Name(s)
Velcade
Intervention Description
Bortezomib, 1.3 mg/m2, s.c., days 1, 4, 8 and 11/cycle. Patients will receive 4 cycles.
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events During NKAE Treatment
Description
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 Outcome Measure Information:
Title
Number of Participants With Peripheral Blood Monoclonal Protein Reduction or Stabilization
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joaquín Martínez López, M.D, Ph.D
Organizational Affiliation
Hospital Universitario 12 de Octubre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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