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Recurrent Multiple MyelomaPhase 1NCT06203912

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

A Phase 1 study testing Biospecimen Collection, Bone Marrow Aspiration and Biopsy and Cyclophosphamide in people with Recurrent Multiple Myeloma and Refractory Multiple Myeloma, run by Elvira Umyarova at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Bone Marrow Aspiration and Biopsy and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
5 Mar 2024to 16 Jun 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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:
  • 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.
  • 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
  • A negative pregnancy test will be required for all WOCBP within 24 hours before starting treatment drugs
  • Breast feeding is not permitted
  • 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
  • Criteria also applies to azoospermic males
  • Males should refrain from sperm donation during this time and continue for 6 months after study treatment ending

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the safety and tolerability of transforming growth factor beta imprinted natural killer cells (TiNK) and isatuximab in patients with multiple myeloma (MM) relapsed or refractory (R/R) to BCMA-targeting therapy.

SECONDARY OBJECTIVES:

  1. To evaluate the objective response rate (ORR) by International Myeloma Working Group (IMWG) criteria of TiNK and isatuximab in patients with MM R/R to BCMA-targeting therapy.

II. To determine the time to response (TTR), time to next therapy (TTNT), the duration of response (DOR), progression free survival (PFS), and overall survival (OS) at 1 year.

III. To determine correlatives of outcomes. IV. To assess quality of life (QOL) with therapy.

OUTLINE: This is a dose-escalation study of TiNK followed by a dose-expansion study.

Patients receive cyclophosphamide intravenously (IV) on day 1, dexamethasone orally (PO) on days 1-4, TiNK IV on day 8, and isatuximab IV on days 8 and 15 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration and biopsy during screening and on study, as well as optionally during follow up. Patients undergo echocardiography (ECHO) during screening and blood sample collection throughout the study.

After completion of study treatment, patients are followed up at 30 days, 60 days. Patients who discontinue study treatment for reasons other than progressive disease follow up every 12 weeks for up to 2 years.

Being tested
Biospecimen Collection, Bone Marrow Aspiration and Biopsy, Cyclophosphamide, Dexamethasone, Echocardiography
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • Bone Marrow Aspiration and BiopsyProcedure or surgery

    Undergo bone marrow aspiration and biopsy

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B-518

    Given IV

  • DexamethasoneDrug

    Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex

    Given PO

  • EchocardiographyProcedure or surgery

    Also called EC

    Undergo echocardiography

  • IsatuximabBiological

    Also called Hu 38SB19, Isatuximab-irfc, SAR 650984, SAR-650984

    Given IV

  • Questionnaire AdministrationOther

    Ancillary study

  • Universal Donor Expanded TGF-beta-imprinted NK CellsBiological

    Also called Allogeneic TGFBi Expanded NK Cells, UD TGF-betai NK Cells, Universal Donor TGF-beta Imprinted Expanded NK Cells

    Given IV

Study groups in NCT06203912
Study groupRoleWhat they receive
Treatment (cyclophosphamide, dexamethasone, TiNK, isatuximab)ExperimentalPatients receive cyclophosphamide IV on day 1, dexamethasone PO on days 1-4, TiNK IV on day 8, and isatuximab IV on days 8 and 15 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration and biopsy during screening and on study, as well as optionally during follow up. Patients undergo ECHO during screening and blood sample collection throughout the study.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy; Drug: Cyclophosphamide; Drug: Dexamethasone; Procedure: Echocardiography; Biological: Isatuximab; Other: Questionnaire Administration; Biological: Universal Donor Expanded TGF-beta-imprinted NK Cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence and severity of adverse events (AE)

    Will use the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 for AE collection. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. The incidence of severe (grade 3+) adverse events or toxicities will be described. We will also assess tolerability of the regimen through assessing the number of patients who required dose modifications and/or dose delays. In addition, we will capture the proportion of patients who go off treatment due to adverse reactions.

    Measured: Up to 60 days after completion of study treatment

Secondary outcomes (8)

  1. Overall response rate (ORR)

    Will be defined as the total number of subjects whose best response is partial response (PR) or better divided by the number of patients. Will be reported overall with 95% binomial exact confidence intervals. Comparison of ORR among patient subgroups will be conducted using Fisher exact test.

    Measured: Up to 2 years after completion of study treatment

  2. Time to response

    Cumulative incidence rates will be calculated and compared using Gray's test accounting for competing risks.

    Measured: From start of treatment until measurement criteria are first met for PR, very good partial response (VGPR), or complete response (CR), assessed up to 2 years after completion of study treatment

  3. Time to next therapy

    Cumulative incidence rates will be calculated and compared using Gray's test accounting for competing risks.

    Measured: From start of treatment until initiation of the next line of therapy, assessed up to 2 years after completion of study treatment

  4. Duration of response

    Will be computed for subjects whose best response is either PR, VGPR, or CR. Will be analyzed using the Kaplan-Meier method.

    Measured: From the time measurement criteria are first met for PR or better (whichever status is recorded first) until the first date of progressive disease or death, assessed up to 2 years after completion of study

  5. Progression free survival

    Will be analyzed using the Kaplan-Meier method.

    Measured: From start of treatment until disease progression or death, at 1 year

  6. Overall survival

    Will be analyzed using the Kaplan-Meier method.

    Measured: From start of treatment to the date of his or her death, at 1 year

  7. Change in quality of life (QOL) using PROMIS G10

    Using the Patient-Reported Outcomes Measurement Information System Global 10 Quality of Life Survey (PROMIS G10 QOL) A repeated measures linear mixed model will be fit to all QOL scores. The response options are presented as 5-point (and single 11-point for pain rating scales). The results of the questions are used to calculate two summary scores.

    Measured: Baseline up to 60 days after completion of study treatment

  8. Change in quality of life (QOL) using EORTC QLQ-MY20

    Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Multiple Myeloma20 (EORTC QLQ - MY20). A repeated measures linear mixed model will be fit to all QOL scores. This incorporates four multi-item scales to assess disease symptoms, side effects of treatment, future perspective and body image. All of the scales and single-item measures range in score from 0 to 100. A high score for the symptom scales represents a high level of symptomatology or problems, whereas a high score for the functional scale represents a high level of functioning.

    Measured: Baseline up to 60 days after completion of study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jan 2024
  2. Study start5 Mar 2024
  3. Primary completion19 May 2026
  4. Study completion16 Jun 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06203912
Sponsor's protocol ID
OSU-23093
Other IDs
NCI-2023-09969
Status last verified
Jun 2026
First submitted
12 Dec 2023
Last updated
1 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biospecimen Collection, Bone Marrow Aspiration and Biopsy and Cyclophosphamide in people with Recurrent Multiple Myeloma and Refractory Multiple Myeloma, run by Elvira Umyarova at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence and severity of adverse events (AE) (time frame: Up to 60 days after completion of study treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06203912.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2026.

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