Clinical Study of Autologous Natural Killer Cells in Multiple Myeloma

Study Overview
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Brief Summary
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Multiple Myeloma (MM) is a lethal disease and at present no available treatment method seems to prevent the disease from progressing or relapsing in the long term. NK cells have a relatively high cytotoxic capacity and an anti tumour effect, suggesting a potential as a treatment of MM.This is a phase I, first-in-human, therapeutic exploratory study, where no benefits for the patients can be guaranteed. However, the theoretical implication is that the infused cells may have a positive antitumour effect for the participating individuals.

Official Title
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A Safety Study of CellProtect, an Autologous ex Vivo Expanded and Activated Natural Killer (NK) Cell Product, in Patients With Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: autologous NK cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Informed Consent Above 18 years of age MM diagnosis (stage I-III according to the International Staging System) Eligible for, and willing to undergo, high dose chemotherapy and ASCT Measurable monoclonal immunoglobulins Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Life expectancy of at least three months Exclusion Criteria: Non-secretory MM Malignancy, other than MM, treated with chemotherapy or radiation within the past six months Blood donation or other significant blood loss within three months from screening Any physical condition or laboratory results that contraindicate a blood donation to be performed within four weeks from screening Any physical condition or laboratory results that require the chemotherapy to start before there is available slot for blood donation Known or suspected allergic reactions to any ingredient of the IP Diagnosis or indication of any active autoimmune disease, such as Rheumatoid Arthritis, Inflammatory Bowel Disease, Systemic Lupus Erythematosis or Multiple Sclerosis Uncontrolled or severe cardiovascular disease, such as myocardial infarction within six months from screening, heart failure (class III or IV according to New York Heart Association), uncontrolled angina, clinically significant pericardial disease or cardiac amyloidosis Poorly controlled hypertension Poorly controlled Diabetes Mellitus, type I or II Diagnosis or indication of any clinically relevant renal disease Diagnosis or indication of any clinically relevant hepatic disease Ongoing infection that is considered chronic Known or suspected drug or alcohol abuse, within 12 months from screening Pregnant, trying to become pregnant, or nursing Lack of, or unreliable contraceptive method, as judged by the Investigator Medical history or any abnormal physical finding that is clinically relevant and could interfere with the safety or objectives of the study, as judged by the Investigator Lack of suitability for participation in the trial, for any reason, as judged by the Investigator

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous NK cells<br>The investigation product is a cell suspension based on ex vivo expanded NK cells from patients with MM. The treatment is strictly autologous. The IP is given as three infusions with escalating doses. Mode of administration Intravenous infusions. Dose levels First infusion; 5x10^6 cells/kg body weight Second infusion; 50x10^6 cells/kg body weight Third infusion; 100x10^6 cells/kg body weight | Drug: autologous NK cells<br>* Autologous ex vivo expanded and activated NK cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) | Assessment of treatment-emergent adverse events/serious adverse events (TEAEs/SEAS)(including IARS). TEAEs are defined as AEs that develop, worsen (according to the Investigators opinion), or bedome serious during the treatment period. | From first dose of study treatment up until six months from last infusion. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes on serum monoclonal immunoglobulin levels as a marker of efficacy | Changes in absolute and relative levels of laboratory parameters | From date of screening through study completion, up until six months from last infusion | 
| Changes on urine monoclonal immunoglobulin levels as a marker of efficacy | Changes in absolute and relative levels of laboratory parameters | From date of screening through study completion, up until six months from last infusion | 
| Changes on serum free light chain levels as a marker of efficacy | Changes in absolute and relative levels of laboratory parameters | From date of screening through study completion, up until six months from last infusion | 
| Effect of CellProtect on plasma cell fraction in bone marrow | Changes in bone marrow clonal plasma cells | From date of screening up until one month from last infusion | 
| Response assessment as defined by the International Myeloma Working Group uniform response criteria | Evaluation of response criteria, i.e. minimal response, partial response, very good partial response and complete response as assessed by International Myeloma Working Group uniform response criteria | From date of screening up until six months from last infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NK cells, Consolidation