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).
調査の概要
状態
研究の種類
入学 (推定)
段階
- フェーズ 1
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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.
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:なし
- 介入モデル:単一グループの割り当て
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的: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.
|
この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
推奨されるフェーズ 2 用量 (RP2D) を確立する
時間枠:最長2年
|
最長2年
|
|
|
Number of Participants with Dose-limiting Toxicity (DLT)
時間枠: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
時間枠: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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
efficacy endpoint: Overall response rate (ORR)
時間枠:Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24
|
Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24
|
|
|
efficacy endpoint: Duration of Response (DoR)
時間枠:Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24
|
Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24
|
|
|
efficacy endpoint: MRD negativity rate
時間枠:Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24
|
Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24
|
|
|
efficacy endpoint: Time to response (TTR)
時間枠:Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24
|
Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24
|
|
|
efficacy endpoint: progression-free survival (PFS)
時間枠:Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24
|
Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24
|
|
|
Efficacy endpoint: Overall survival (OS)
時間枠:Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24
|
Assessment at months 1, 2, 3, 6, 9, 12, 18, and 24
|
|
|
Concentration of CAR-T cells after Infusion (PK)
時間枠: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)
時間枠: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
時間枠:Up to 2 years
|
Up to 2 years
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- DQ1001-IIT-001
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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