- ICH GCP
- Yhdysvaltain kliinisten tutkimusten rekisteri
- Kliininen tutkimus NCT07622862
Exploratory Clinical Trial of DQ1001 in Relapsed or Refractory Multiple Myeloma (RRMM)
An Early Exploratory Clinical Trial Evaluating the Safety, Tolerability, and Preliminary Efficacy of DQ1001-a Universal Allogeneic CAR-T Cell Infusion Targeting Both BCMA and GPRC5D-in Patients With Relapsed or Refractory Multiple Myeloma (RRMM).
Tutkimuksen yleiskatsaus
Tila
Opintotyyppi
Ilmoittautuminen (Arvioitu)
Vaihe
- Vaihe 1
Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
- Aikuinen
- Vanhempi Aikuinen
Hyväksyy terveitä vapaaehtoisia
Kuvaus
Inclusion Criteria:
- Voluntary signing of the Informed Consent Form (ICF) prior to undergoing any study-related procedures.
- Age at the time of ICF signing is between 18 and 70 years inclusive.
Diagnosis of relapsed or refractory multiple myeloma (MM), per IMWG criteria:
Prior receipt of at least three lines of therapy;
- Documented progressive disease (PD) during the most recent therapy or within two months after its completion, or documented failure to achieve at least minimal response (MR) within two months after the most recent therapy.
- Tumor cells in bone marrow or peripheral blood are BCMA/GPRC5D-positive by flow cytometry; or tumor tissue is BCMA/GPRC5D-positive by immunohistochemistry.
Presence of measurable disease at screening, defined as any one of the following:
- For IgG-type MM: serum monoclonal M-protein ≥10 g/L; for IgA-, IgD-, IgE-, or IgM-type MM: serum monoclonal M-protein ≥5 g/L; or
- Urinary M-protein ≥200 mg/24 h; or
- Light-chain MM: involved serum free light chain (FLC) ≥100 mg/L and abnormal serum FLC κ/λ ratio (<0.26 or >1.65).
- ECOG performance status score of 0-2.
- Expected survival ≥12 weeks.
- Men with reproductive potential and women of childbearing potential must agree to use effective contraception from the time of ICF signing through two years after the last dose of study drug. Women of childbearing potential include premenopausal women and women within two years of menopause. A negative serum pregnancy test is required at screening for women of childbearing potential.
- For patients who previously underwent hematopoietic stem cell transplantation: no active graft-versus-host disease (GVHD), and systemic immunosuppressants discontinued for at least four weeks.
Adequate major organ function, defined as follows:
- Hematologic: absolute neutrophil count (ANC) ≥1.0 × 10⁹/L; hemoglobin ≥70 g/L; platelet count ≥50 × 10⁹/L; lymphocyte count >0.2 × 10⁹/L;
- Coagulation: fibrinogen ≥1.0 g/L; activated partial thromboplastin time (APTT) ≤1.5 × upper limit of normal (ULN); prothrombin time (PT) ≤1.5 × ULN;
- Hepatic: total bilirubin ≤2 × ULN (≤3 × ULN in patients with Gilbert syndrome); aspartate aminotransferase (AST) ≤3 × ULN; alanine aminotransferase (ALT) ≤3 × ULN;
- Cardiopulmonary: left ventricular ejection fraction ≥50%; peripheral capillary oxygen saturation ≥92% without supplemental oxygen, or ≥95% with supplemental oxygen;
- Renal: estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m² (calculated using the CKD-EPI equation).
- Investigator judgment that the participant is able to comply with protocol requirements and complete treatment and follow-up.
Exclusion Criteria:
- Central nervous system (CNS) metastases, leptomeningeal disease, or metastatic CNS compression; or a prior history of CNS disorders, including but not limited to epilepsy, hemiplegia, aphasia, stroke, severe traumatic brain injury, dementia, or Parkinson's disease.
- Prior treatment with CAR-T therapy or drugs targeting BCMA or GPRC5D.
- Active or moderate-to-severe chronic graft-versus-host disease (GVHD) within four weeks prior to signing the informed consent form (ICF), or systemic GVHD-directed therapy within four weeks before the first infusion.
- Any investigational drug or systemic antitumor therapy administered within 28 days (or five half-lives of the drug, whichever is deemed more appropriate by the investigator) prior to the first infusion.
- Extensive radiotherapy administered within 28 days prior to signing the ICF; localized palliative radiotherapy to non-target lesions is permitted if administered within 14 days prior to signing the ICF or anticipated during the study period.
- Major surgical procedure performed within 28 days prior to signing the ICF, or planned major surgery during the study period.
- Positive hepatitis B surface antigen (HBsAg) at screening; or negative HBsAg but positive hepatitis B core antibody (HBcAb) with detectable hepatitis B virus (HBV) DNA in peripheral blood; positive hepatitis C virus (HCV) antibody and HCV RNA; positive human immunodeficiency virus (HIV) antibody; positive cytomegalovirus (CMV) DNA; or positive for both treponemal and non-treponemal antibodies for syphilis.
- Known hypersensitivity to any component of the study drugs, including but not limited to lymphodepleting agents (e.g., tocilizumab, cyclophosphamide, fludarabine) or contrast agents used for imaging studies.
- Severe respiratory disease (including but not limited to severe or very severe chronic obstructive pulmonary disease, interstitial lung disease); or significant cardiovascular history (including but not limited to coronary artery bypass grafting or percutaneous coronary intervention within six months prior to signing the ICF, myocardial infarction, New York Heart Association [NYHA] Class III-IV congestive heart failure, unstable angina, corrected QT interval (QTcF) > 480 ms, personal or familial history of long or short QT syndrome, uncontrolled severe arrhythmia or hypertension requiring pharmacologic management).
- Any comorbidity or other condition judged by the investigator to potentially compromise adherence to the study protocol or render the participant unsuitable for participation in this study.
- Pregnant or lactating women, or women planning pregnancy or unwilling to use highly effective, reliable contraception during the study and for two years following completion of study treatment.
- Uncontrolled active infection (excluding those viral infections listed above), including but not limited to serious bacterial, fungal, or other viral infections deemed by the investigator to increase the risk associated with study treatment.
- Receipt of a live attenuated viral vaccine within one month prior to signing the ICF.
- History of immunodeficiency disorder or active autoimmune disease (patients with stable autoimmune disease at enrollment who have not required systemic immunosuppressive therapy for ≥6 months are exempted).
- Diagnosis of any malignancy other than multiple myeloma within the past two years prior to screening, except for: malignancies treated with curative intent and without evidence of active disease for ≥2 years prior to enrollment; adequately treated non-melanoma skin cancer with no current evidence of disease; or carcinoma in situ treated with curative intent.
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Ei käytössä
- Inventiomalli: Yksittäinen ryhmätehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
|---|---|
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Kokeellinen: DQ1001 Treatment Group
|
Patients received fludarabine and cyclophosphamide lymphodepleting preconditioning for three consecutive days-from day -5 (D-5) to day -3 (D-3)-prior to intravenous infusion of DQ1001.
|
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Määritä suositeltu vaiheen 2 annos (RP2D)
Aikaikkuna: Jopa 2 vuotta
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Jopa 2 vuotta
|
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Number of Participants with Dose-limiting Toxicity (DLT)
Aikaikkuna: Within 28 days after the infusion of DQ1001
|
DLT refers to drug-related toxicities that occur during treatment, the severity of which is clinically unacceptable, thereby restricting further dose escalation. All adverse events are assessed and graded by the investigator according to the NCI-CTCAE version 6.0. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are graded per the ASTCT criteria, and acute graft-versus-host disease (aGVHD) per the MAGIC criteria. |
Within 28 days after the infusion of DQ1001
|
|
Number of Participants with Adverse Events (AEs) by Severity
Aikaikkuna: Up to 2 years
|
An adverse event is any untoward medical occurrence in a clinical study participant that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 6.0.
Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are graded per the ASTCT criteria, and acute graft-versus-host disease (aGVHD) per the MAGIC criteria.
|
Up to 2 years
|
Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
efficacy endpoint: Overall response rate (ORR)
Aikaikkuna: Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24
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Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24
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efficacy endpoint: Duration of Response (DoR)
Aikaikkuna: Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24
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Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24
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efficacy endpoint: MRD negativity rate
Aikaikkuna: Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24
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Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24
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efficacy endpoint: Time to response (TTR)
Aikaikkuna: Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24
|
Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24
|
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efficacy endpoint: progression-free survival (PFS)
Aikaikkuna: Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24
|
Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24
|
|
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Efficacy endpoint: Overall survival (OS)
Aikaikkuna: Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24
|
Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24
|
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Concentration of CAR-T cells after Infusion (PK)
Aikaikkuna: Up to 2 years
|
Flow cytometry is used to determine the percentage and absolute count of CAR-T cells in peripheral blood, and polymerase chain reaction (PCR) is used to measure CAR copy numbers.
|
Up to 2 years
|
|
Lymphocyte Subsets and Concentration of Cytokine after Infusion (PD)
Aikaikkuna: Up to 2 years
|
Assessment of lymphocyte subsets (CD3+ T cells, CD4+ cells, CD8+ cells, etc.), CAR-T-related cytokines (IL-6, IL-8, IL-10, IL-2R, TNF-α, IFN-γ, IL-1β, ferritin, C-reactive protein, etc.), as well as CAR-T cell subset analysis and exhaustion markers.
|
Up to 2 years
|
|
Anti-DQ1001 antibodies in peripheral blood
Aikaikkuna: Up to 2 years
|
Up to 2 years
|
Yhteistyökumppanit ja tutkijat
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Arvioitu)
Ensisijainen valmistuminen (Arvioitu)
Opintojen valmistuminen (Arvioitu)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Todellinen)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
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