Giving NT-I7 after CAR T-cell Therapy for the Treatment of Relapsed or Refractory Multiple Myeloma
This phase Ib trial tests the safety, best dose, and effectiveness of NT-I7 given after standard chimeric antigen receptor (CAR) T-cell therapy in patients with multiple myeloma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). NT-I7 is a modified form of a human protein called interleukin-7. It stimulates the growth, function, and survival of a type of immune cell called T-cells, which enhances the body's anti-tumor immune response. Giving NT-I7 after standard CAR T-cell therapy may be safe may improve the effectiveness of the CAR T-cell treatment in patients with relapsed or refractory multiple myeloma.
Inclusion Criteria
- Diagnosis of multiple myeloma with measurable disease by IMWG criteria
- Eligible for standard of care, Food and Drug Administration (FDA)-approved BCMA CAR-T cell therapy with ciltacabtagene autoleucel * Patients enrolling in the dose escalation stage must have received at least two prior lines of treatment and be penta-drug exposed (i.e. exposure to at least 5 active anti-myeloma drugs, excluding corticosteroids and melphalan and including, at minimum, a proteasome inhibitor, an immunomodulatory drug, and a CD38 monoclonal antibody)
- Life expectancy >= 12 weeks per assessment from the enrolling physician
- At least 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Total bilirubin =< 1.5 x institutional upper limit of normal (IULN)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x IULN
- Creatinine clearance > 30 mL/min by Cockcroft-Gault
- The effects of NT-I7 on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry until 90 days after completion of NT-I7 therapy/placebo (corresponding to day 125 post CAR-T). Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform her treating physician immediately
- Ability to understand and willingness to sign an Institutional Review Board (IRB) approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants
Exclusion Criteria
- Received prior BCMA-directed therapy
- Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial
- Currently receiving or have received any other investigational agents within 14 days prior to CAR-T infusion
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to NT-I7 or other agents used in the study
- Uncontrolled intercurrent illness including but not limited to: ongoing or active infection (bacterial, fungal, viral, or tuberculosis, including known hepatitis A, B, or C, or HIV [testing not required]), symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia (except well-controlled atrial fibrillation). Patients with a known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association function classification; to be eligible for this trial, patients should be a class 2B or better
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to starting CAR-T therapy
- Receipt of live, attenuated vaccine within 30 days prior to first day of treatment
- Had an allogeneic tissue/solid organ transplant or allogeneic stem cell transplant
- Not able to receive intramuscular therapy
- Prior history of T cell malignancy
- Prior history of congenital immunodeficiency syndrome
- Prior history of autoimmune disease with significant disease activity in the past 2 years, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Sézary syndrome, vasculitis or glomerulonephritis, Bell’s palsy, Guillain-Barré syndrome, or multiple sclerosis
- Prior history of plasma cell leukemia, systemic amyloidosis, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, or multiple myeloma with central nervous system (CNS) involvement
- Planning to start maintenance therapy prior to day 100 post-CAR-T therapy
- A history of clinically significant pulmonary disorders, such as severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, symptomatic pulmonary embolism within 3 months prior to study enrollment, or active or prior interstitial lung disease/pneumonitis
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07200089.
Locations matching your search criteria
United States
Missouri
Saint Louis
PRIMARY OBJECTIVES:
I. To evaluate the safety and toxicity of efineptakin alfa (NT-I7) treatment in multiple myeloma (MM) following B-cell maturation antigen (BCMA) CAR-T therapy.
II. To determine the recommended phase II dose (RP2D). (Dose escalation stage only)
SECONDARY OBJECTIVES:
I. To determine myeloma response by International Myeloma Working Group (IMWG) criteria and minimal residual disease (MRD) negativity.
II. To determine the rate and severity of cytokine release syndrome (CRS) and immune-effector cell associated neurotoxicity syndrome (ICANS).
III. To determine the cumulative incidence of non-relapse mortality (NRM).
TERTIARY/EXPLORATORY OBJECTIVES:
I. To assess CAR-T cell expansion, persistence, immune-phenotype and cytokine release kinetics.
II. To assess soluble BCMA in plasma as a surrogate marker of CAR T persistence and disease response.
III. To evaluate NT-I7 immunogenicity.
OUTLINE: This is dose-escalation study of NT-I7 followed by a dose-expansion study.
DOSE-ESCALATION: Patients receive NT-I7 intramuscularly (IM) on days 14 and 35 following their standard of care (SOC) BCMA CAR-T cell infusion (day 0). Patients also undergo collection of blood samples and bone marrow biopsy/aspiration throughout the trial.
DOSE-EXPANSION: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive NT-I7 IM on days 14 and 35 following their SOC BCMA CAR-T cell infusion (day 0) as in the dose-escalation stage. Patients also undergo collection of blood samples and bone marrow biopsy/aspiration throughout the trial.
ARM II: Patients receive placebo IM on days 14 and 35 following their SOC BCMA CAR-T cell infusion (day 0). Patients also undergo collection of blood samples and bone marrow biopsy/aspiration throughout the trial.
After completion of study treatment, patients are followed up on days 42, 65, 100, and 365.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationSiteman Cancer Center at Washington University
Principal InvestigatorMichael Joseph Slade
- Primary ID202601207
- Secondary IDsNCI-2026-02510
- ClinicalTrials.gov IDNCT07200089