ACTIVE_NOT_RECRUITING

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

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Conditions

Recurrent Multiple MyelomaRefractory Multiple Myeloma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase Ib Study of TGFbi NK Cells and Isatuximab for Myeloma Relapsed/Refractory to BCMA Targeting Therapy

Quick Facts

Study Start:2024-03-05
Study Completion:2026-01-31
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:ACTIVE_NOT_RECRUITING

Study ID

NCT06203912

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * 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:
  2. * Serum M-protein ≥ 0.5 g/dl
  3. * Urine monoclonal protein ≥ 200 mg/24h
  4. * Involved free light chain (FLC) level ≥ 10mg/dl (≥ 100mg/l) and an abnormal serum free light chain ratio (\< 0.26, or \> 1.65)
  5. * 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.
  6. * Prior daratumumab or isatuximab is permitted but not in the immediate line prior to study entry
  7. * Prior autologous hematopoietic cell transplant is permitted
  8. * Prior allogeneic transplant is excluded
  9. * Refractory (progressed on or within 60 days of treatment) to their last treatment
  10. * 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
  11. * Patients must be off last treatment for at least 2 weeks by the beginning of treatment on this protocol
  12. * Hemoglobin ≥ 7g/dL
  13. * Absolute neutrophil count (ANC) ≥ 1000/µL
  14. * Platelets ≥ 70,000/µL
  15. * If plasma cell percentage on bone marrow biopsy core is \> 30%, platelet requirement will be adjusted to 50,000/µl
  16. * Total bilirubin \< 2 mg/dL
  17. * Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT)/ alkaline phosphatase \< 2.5 X the upper limit of normal (ULN)
  18. * Calculated creatinine clearance of ≥ 30ml/min using Modification of Diet in Renal Disease (MDRD) formula
  19. * 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
  20. * No uncontrolled arrhythmias
  21. * No New York Heart Association class III-IV heart failure
  22. * 12-lead electrocardiogram (ECG) with QT interval calculated by Fridericia Formula (QTcF) interval of ≤ 470 msec
  23. * Patients must provide informed consent
  24. * Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of ≤ 2
  25. * Fertility requirements:
  26. * Women of child bearing potential (WOCBP) must commit to either abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously. This includes one highly effective form of contraception (tubal ligation, intrauterine device \[IUD\], hormonal \[birth control pills, injections, hormonal patches, vaginal rings or implants\] or partner's vasectomy) and one additional effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical cap). Contraception must begin 4 weeks prior to dosing and continue to 6 months after study treatment ending. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy.
  27. * Investigators shall counsel WOCBP and male participants who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy
  28. * A negative pregnancy test will be required for all WOCBP within 24 hours before starting treatment drugs
  29. * Breast feeding is not permitted
  30. * Male patients must agree to use an adequate method of contraception (latex or synthetic condom) for the duration of the study and up to 6 months after study treatment ending
  31. * Criteria also applies to azoospermic males
  32. * Males should refrain from sperm donation during this time and continue for 6 months after study treatment ending
  1. * Patients with active (untreated or relapsed) central nervous system (CNS) MM
  2. * Patients with Waldenstrom macroglobulinemia, primary AL amyloidosis, primary plasma cell leukemia, or polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome
  3. * Patients with secondary plasma cell leukemia are permitted
  4. * Patients receiving concurrent corticosteroids at the time protocol therapy is initiated other than for physiologic maintenance treatment
  5. * Concurrent use of complementary or alternative medicines that would confound the interpretation of toxicities and antitumor activity of the study drugs
  6. * Patients with contraindications or allergy to cyclophosphamide and/or daratumumab/isatuximab
  7. * Unacceptable respiratory risk factors defined by any one of the following criteria:
  8. * Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) less than 50% of predicted normal
  9. * Moderate or severe persistent asthma within the past 2 years, or currently has uncontrolled asthma of any classification
  10. * Unacceptable cardiac risk factors defined by any of the following criteria:
  11. * Complete left bundle branch, bifascicular block or clinically significant abnormal electrocardiogram (EKG) finding at screening
  12. * Congenital long QT Syndrome
  13. * Myocardial infarction or unstable angina within 6 months
  14. * 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
  15. * Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from the side-effects of surgery
  16. * Patients with known positivity for human immunodeficiency virus (HIV) or active hepatitis B/C
  17. * Patients with chronic hepatitis B infection may be enrolled but must be provided prophylaxis (ex. entecavir for one year from start of therapy)
  18. * 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
  19. * 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
  20. * 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
  21. * Life expectancy of 6 months or less

Contacts and Locations

Principal Investigator

Elvira Umyarova, MD
PRINCIPAL_INVESTIGATOR
Ohio State University Comprehensive Cancer Center

Study Locations (Sites)

Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
United States

Collaborators and Investigators

Sponsor: Elvira Umyarova

  • Elvira Umyarova, MD, PRINCIPAL_INVESTIGATOR, Ohio State University Comprehensive Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-03-05
Study Completion Date2026-01-31

Study Record Updates

Study Start Date2024-03-05
Study Completion Date2026-01-31

Terms related to this study

Additional Relevant MeSH Terms

  • Recurrent Multiple Myeloma
  • Refractory Multiple Myeloma