Clinical Study of Autologous Natural Killer Cells in Multiple Myeloma

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

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.

Study Overview

• Status: Unknown
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: autologous NK cells

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 141 57
    • Karolinska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed Informed Consent
2. Above 18 years of age
3. MM diagnosis (stage I-III according to the International Staging System)
4. Eligible for, and willing to undergo, high dose chemotherapy and ASCT
5. Measurable monoclonal immunoglobulins
6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
7. Life expectancy of at least three months

Exclusion Criteria:

1. Non-secretory MM
2. Malignancy, other than MM, treated with chemotherapy or radiation within the past six months
3. Blood donation or other significant blood loss within three months from screening
4. Any physical condition or laboratory results that contraindicate a blood donation to be performed within four weeks from screening
5. Any physical condition or laboratory results that require the chemotherapy to start before there is available slot for blood donation
6. Known or suspected allergic reactions to any ingredient of the IP
7. Diagnosis or indication of any active autoimmune disease, such as Rheumatoid Arthritis, Inflammatory Bowel Disease, Systemic Lupus Erythematosis or Multiple Sclerosis
8. 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
9. Poorly controlled hypertension
10. Poorly controlled Diabetes Mellitus, type I or II
11. Diagnosis or indication of any clinically relevant renal disease
12. Diagnosis or indication of any clinically relevant hepatic disease
13. Ongoing infection that is considered chronic
14. Known or suspected drug or alcohol abuse, within 12 months from screening
15. Pregnant, trying to become pregnant, or nursing
16. Lack of, or unreliable contraceptive method, as judged by the Investigator
17. 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
18. Lack of suitability for participation in the trial, for any reason, as judged by the Investigator

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Autologous NK cells; 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; Autologous ex vivo expanded and activated NK cells

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Karolinska University Hospital
• Investigators: Principal Investigator: Hareth Nahi, M.D., Karolinska University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2014
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: September 10, 2020
• First Submitted That Met QC Criteria: September 16, 2020
• First Posted (Actual): September 22, 2020

Study Record Updates

• Last Update Posted (Actual): February 17, 2021
• Last Update Submitted That Met QC Criteria: February 16, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: NK cells; Consolidation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: ACP-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No