Clinical Study of Autologous Natural Killer Cells in Multiple Myeloma

• ClinicalTrials.gov Identifier: NCT04558853
• Recruitment Status: Active, not recruiting
• First Posted: September 22, 2020
• Last Update Posted: September 22, 2020
• Sponsor: Karolinska University Hospital
• Information provided by (Responsible Party): Hareth Nahi, Karolinska University Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Drug: autologous NK cells	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Safety Study of CellProtect, an Autologous ex Vivo Expanded and Activated Natural Killer (NK) Cell Product, in Patients With Multiple Myeloma
• Actual Study Start Date: January 1, 2014
• Estimated Primary Completion Date: December 31, 2020
• Estimated Study Completion Date: December 31, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [ Time Frame: From first dose of study treatment up until six months from last infusion. ]
   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.

Secondary Outcome Measures :

1. Changes on serum monoclonal immunoglobulin levels as a marker of efficacy [ Time Frame: From date of screening through study completion, up until six months from last infusion ]
   Changes in absolute and relative levels of laboratory parameters
2. Changes on urine monoclonal immunoglobulin levels as a marker of efficacy [ Time Frame: From date of screening through study completion, up until six months from last infusion ]
   Changes in absolute and relative levels of laboratory parameters
3. Changes on serum free light chain levels as a marker of efficacy [ Time Frame: From date of screening through study completion, up until six months from last infusion ]
   Changes in absolute and relative levels of laboratory parameters
4. Effect of CellProtect on plasma cell fraction in bone marrow [ Time Frame: From date of screening up until one month from last infusion ]
   Changes in bone marrow clonal plasma cells
5. Response assessment as defined by the International Myeloma Working Group uniform response criteria [ Time Frame: From date of screening up until six months from last infusion ]
   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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Sweden

Karolinska University Hospital

Stockholm, Sweden, 141 57

Sponsors and Collaborators

Karolinska University Hospital

Investigators

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

More Information

• Responsible Party: Hareth Nahi, Principal Investigator, Karolinska University Hospital
• ClinicalTrials.gov Identifier: NCT04558853
• Other Study ID Numbers: ACP-001
• First Posted: September 22, 2020
• Last Update Posted: September 22, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hareth Nahi, Karolinska University Hospital:

NK cells; Consolidation

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases