Multiple MyelomaPhase 1NK-VS-MMNCT02481934
Clinical Trial of Expanded and Activated Autologous NK Cells to Treat Multiple Myeloma
A Phase 1 study testing NKAE cells infusion, Lenalidomide and Bortezomib in people with Multiple Myeloma, run by Joaquín Martínez López, MD, PhD at 1 site in Spain.
Trial 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 more about this study
- Who is it for?
- Ages 20 to 80 years
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- NKAE cells infusion, Lenalidomide and Bortezomib
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteSpain
- Study dates
- Mar 2013to Oct 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
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.
- Conditions
- Multiple Myeloma
- Being tested
- NKAE cells infusion, Lenalidomide, Bortezomib
- Keywords
- Recurrent multiple myeloma, NK cells, cell therapy, NKAE, Relapsed multiple myeloma
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NKAE cells infusionProcedure or surgery
Also called NKAE infusion, Activated and expanded autologous NK 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.
LenalidomideDrug
Also called Revlimid
Lenalidomide, 10 mg oral/day during 21 days (cycle). Patients will receive 4 cycles.
BortezomibDrug
Also called Velcade
Bortezomib, 1.3 mg/m2, s.c., days 1, 4, 8 and 11/cycle. Patients will receive 4 cycles.
| Study group | Role | What they receive |
|---|---|---|
| NKAE cells infusion + chemotherapy | Experimental | Expanded and activated autologous NK cells (NKAEs) + chemotherapy (lenalidomide OR bortezomib). Receives: Procedure: NKAE cells infusion; Drug: Lenalidomide; Drug: Bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 16 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2015 (estimated)
- Study startMar 2013
- Primary completionJul 2016
- Study completionOct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Joaquín Martínez López, MD, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Infantil Universitario Niño Jesús, Madrid, Spain
- Responsible party
- Sponsor-investigator, Joaquín Martínez López, MD, PhD, Hospital Universitario 12 de Octubre
- Investigators
- Joaquín Martínez López, M.D, Ph.D, Principal investigator, Hospital Universitario 12 de Octubre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02481934
- Sponsor's protocol ID
- NK-VS-MM
- Acronym
- NK-VS-MM
- Status last verified
- Aug 2021
- First submitted
- 10 Jun 2015
- Last updated
- 20 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT02481934
- Acronym / sponsor ID
- NK-VS-MM / NK-VS-MM
- Conditions
- Multiple Myeloma
- Keywords
- Recurrent multiple myeloma, NK cells, cell therapy, NKAE, Relapsed multiple myeloma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Joaquín Martínez López, MD, PhDUniversity, hospital or other
- Collaborators
- Hospital Infantil Universitario Niño Jesús, Madrid, Spain
- Study start
- Mar 2013
- Primary completion
- Jul 2016 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 25 Jun 2015 (estimated)
- Results
- Posted 5 Dec 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NKAE cells infusion + chemotherapy | Experimental | Procedure: NKAE cells infusion, Drug: Lenalidomide, Drug: BortezomibExpanded and activated autologous NK cells (NKAEs) + chemotherapy (lenalidomide OR bortezomib). |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NKAE cells infusionAlso: NKAE infusion, Activated and expanded autologous NK cells infusionExpanded 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. | Procedure or surgery | NKAE cells infusion + chemotherapy |
| LenalidomideAlso: RevlimidLenalidomide, 10 mg oral/day during 21 days (cycle). Patients will receive 4 cycles. | Drug | NKAE cells infusion + chemotherapy |
| BortezomibAlso: VelcadeBortezomib, 1.3 mg/m2, s.c., days 1, 4, 8 and 11/cycle. Patients will receive 4 cycles. | Drug | NKAE cells infusion + chemotherapy |
Primary outcome
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.
1 secondary outcome
Number of Participants With Peripheral Blood Monoclonal Protein Reduction or Stabilization
Time frame: 16 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joaquín Martínez López, M.D, Ph.D principal investigator
Hospital Universitario 12 de Octubre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NKAE cells infusion, Lenalidomide and Bortezomib in people with Multiple Myeloma, run by Joaquín Martínez López, MD, PhD at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events During NKAE Treatment (time frame: 16 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2021.