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

NCT06203912 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-23093NCI-2023-09969
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Recurrent Multiple Myeloma; Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (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.

  Up to 60 days after completion of study treatment

Secondary Outcomes (8)

• Overall response rate (ORR)

  Up to 2 years after completion of study treatment

• Time to response

  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

• Time to next therapy

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

• Duration of response

  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

• Progression free survival

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

Study Arms (1)

Treatment (cyclophosphamide, dexamethasone, TiNK, isatuximab)

EXPERIMENTAL

Patients 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.

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

Interventions

Bone Marrow Aspiration and Biopsy PROCEDURE

Undergo bone marrow aspiration and biopsy

Treatment (cyclophosphamide, dexamethasone, TiNK, isatuximab)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B-518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719, WR-138719

Treatment (cyclophosphamide, dexamethasone, TiNK, isatuximab)

Dexamethasone DRUG

Given PO

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hemady, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Treatment (cyclophosphamide, dexamethasone, TiNK, isatuximab)

Echocardiography PROCEDURE

Undergo echocardiography

Also known as: EC

Treatment (cyclophosphamide, dexamethasone, TiNK, isatuximab)

Isatuximab BIOLOGICAL

Given IV

Also known as: Hu 38SB19, Isatuximab-irfc, SAR 650984, SAR-650984, SAR650984, Sarclisa

Treatment (cyclophosphamide, dexamethasone, TiNK, isatuximab)

Questionnaire Administration OTHER

Ancillary study

Treatment (cyclophosphamide, dexamethasone, TiNK, isatuximab)

Universal Donor Expanded TGF-beta-imprinted NK Cells BIOLOGICAL

Given IV

Also known as: Allogeneic TGFBi Expanded NK Cells, UD TGF-betai NK Cells, Universal Donor TGF-beta Imprinted Expanded NK Cells

Treatment (cyclophosphamide, dexamethasone, TiNK, isatuximab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (cyclophosphamide, dexamethasone, TiNK, isatuximab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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

Sponsors & Collaborators

• Elvira Umyarova: lead
• Sanofi: collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Specimen Handling; Biopsy; Cyclophosphamide; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; isatuximab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Elvira Umyarova, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 12, 2023
• First Posted: January 12, 2024
• Study Start: March 5, 2024
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)