Donor Immune Cells (TGFbi NK Cells) and Isatuximab for the Treatment of Relapsed or Refractory Multiple Myeloma

Completed · Phase 1

Conditions studied: Recurrent Multiple Myeloma, Refractory Multiple Myeloma

In brief

This phase I trial tests the side effects and best dose of TGFbi natural killer (NK) cells (TiNK) when given together with isatuximab for the treatment of patients with multiple myeloma that has come back after a period of improvement (relapsed) or that has not responded to treatment (refractory). NK cells are a type of white blood cell that are known to spontaneously attack cancer cells. TiNK are NK cells made in a laboratory to have a higher response to tumor cells. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as isatuximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Patients also receive standard treatment (cyclophosphamide and dexamethasone) on this trial. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill cancer cells. It may also lower the body's immune response. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Giving TiNK and isatuximab with standard treatment may be a safe and effective treatment for relapsed or refractory multiple myeloma.

Key facts

Study ID

NCT06203912

Run by

Elvira Umyarova

People needed

3

Starts

2024-03-05

Expected to finish

2026-06-16

Last updated by the study team

2026-07-01

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients 18 years of age or older with evidence of relapsed or refractory disease as defined by IMWG criteria and measurable disease as defined by any of the following:
• Serum M-protein ≥ 0.5 g/dl
• Urine monoclonal protein ≥ 200 mg/24h
• Involved free light chain (FLC) level ≥ 10mg/dl (≥ 100mg/l) and an abnormal serum free light chain ratio (< 0.26, or > 1.65)
• Patients must have had at least 3 prior lines of therapy including lenalidomide, proteasome inhibitor (PI), anti-CD38 or anti-SLAMF7 directed antibody, and BCMA-targeting therapy.
• Prior daratumumab or isatuximab is permitted but not in the immediate line prior to study entry
• Prior autologous hematopoietic cell transplant is permitted
• Prior allogeneic transplant is excluded
• Refractory (progressed on or within 60 days of treatment) to their last treatment
• If chimeric antigen receptor t cell (CAR-T) therapy was the immediately prior therapy, then the definition of refractory disease will not be limited to within 60 days
• Patients must be off last treatment for at least 2 weeks by the beginning of treatment on this protocol
• Hemoglobin ≥ 7g/dL
• Absolute neutrophil count (ANC) ≥ 1000/µL
• Platelets ≥ 70,000/µL
• If plasma cell percentage on bone marrow biopsy core is > 30%, platelet requirement will be adjusted to 50,000/µl
• Total bilirubin < 2 mg/dL
• Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT)/ alkaline phosphatase < 2.5 X the upper limit of normal (ULN)
• Calculated creatinine clearance of ≥ 30ml/min using Modification of Diet in Renal Disease (MDRD) formula
• Left ventricular ejection fraction ≥ 30%; baseline echocardiography (ECHO) is not required if ECHO was done within the preceding one year and patients do not have new signs/symptoms suggestive of heart failure
• No uncontrolled arrhythmias
• No New York Heart Association class III-IV heart failure
• 12-lead electrocardiogram (ECG) with QT interval calculated by Fridericia Formula (QTcF) interval of ≤ 470 msec
• Patients must provide informed consent
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of ≤ 2
• Fertility requirements:

You may not qualify if…

• Patients with active (untreated or relapsed) central nervous system (CNS) MM
• Patients with Waldenstrom macroglobulinemia, primary AL amyloidosis, primary plasma cell leukemia, or polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome
• Patients with secondary plasma cell leukemia are permitted
• Patients receiving concurrent corticosteroids at the time protocol therapy is initiated other than for physiologic maintenance treatment
• Concurrent use of complementary or alternative medicines that would confound the interpretation of toxicities and antitumor activity of the study drugs
• Patients with contraindications or allergy to cyclophosphamide and/or daratumumab/isatuximab
• Unacceptable respiratory risk factors defined by any one of the following criteria:
• Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) less than 50% of predicted normal
• Moderate or severe persistent asthma within the past 2 years, or currently has uncontrolled asthma of any classification
• Unacceptable cardiac risk factors defined by any of the following criteria:
• Complete left bundle branch, bifascicular block or clinically significant abnormal electrocardiogram (EKG) finding at screening
• Congenital long QT Syndrome
• Myocardial infarction or unstable angina within 6 months
• Patients who have received targeted or investigational agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is shorter) and who have not recovered from side effects of those therapies
• Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from the side-effects of surgery
• Patients with known positivity for human immunodeficiency virus (HIV) or active hepatitis B/C
• Patients with chronic hepatitis B infection may be enrolled but must be provided prophylaxis (ex. entecavir for one year from start of therapy)
• Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention, other than non-melanoma skin cancer and carcinoma in situ of the cervix or breast, should not be enrolled
• Patients with any significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to them by the study staff
• Any other medical condition, including mental illness or substance abuse, deemed by the investigator(s) to likely interfere with the patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
• Life expectancy of 6 months or less

Where it is running

• Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States

Full record on ClinicalTrials.gov

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