NCT07099391招募中1 期
ALTITUDE - ALTernating Induction Therapies to Achieve Undetectable Disease Endpoints: A Phase 1/2 Alternating Dara-RVd/Teclistamab-RVd in Transplant Eligible Standard-risk Newly Diagnosed Multiple Myeloma
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 65
- 试验地点
- 13
- 主要终点
- Phase I: Toxicity
研究概览
简要总结
The purpose of this study is to find out whether Tec-RVd (teclistamab, lenalidomide, bortezomib, and dexamethasone) after 3 treatment Cycles of Dara-RVd (daratumumab, lenalidomide, bortezomib, and dexamethasone) is a safe treatment for people with newly diagnosed multiple myeloma (MM).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented multiple myeloma satisfying the International Myeloma Working Group (IMWG) diagnostic criteria36 (evidence of myeloma defining event attributed to underlying plasma cell disorder) with measurable disease defined as:
- •Clonal plasma cells in the bone marrow ≥ 10% or presence of a biopsy proven plasmacytoma
- •Measurable disease within the past 4 weeks defined by any of the following:
- •IgG myeloma: Serum monoclonal protein ≥ 1.0 g/dL or urine monoclonal protein ≥ 200 mg/24 hr; or
- •IgA, IgM, IgD, IgE multiple myeloma: serum M-protein ≥ 0.5 g/dL or urine monoclonal protein ≥ 200 mg/24 hr; or
- •Light chain multiple myeloma: Involved serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum free kappa/lambda light chain ratio
- •Measurable plasmacytomas seen on imaging (≥ 1 lesion that has a single diameter ≥ 2 cm). If this is the primary marker of measurable disease, patients will need a biopsy at screening.
- •Bone marrow plasma cells ≥ 30% as determined by CD138 immunohistochemistry staining.
- •Standard risk multiple myeloma - excluding patients with high risk cytogenetic abnormality (HRCA) according to the IMS/IMWG 2024 Consensus Definition:
- •TP53 mutation and/or del(17p) with cancer clonal function (CCF) >20% by analyses conducted on CD138+ purified cells
- •t(4;14), t(14;16), or t(14;20) co-occurring with +1q (gain/amp 1q) and/or del(1p)
- •Monoallelic del(1p32) with +1q or biallelic del(1p32)
- •High Beta-2 microglobulin (>5.5 mg/dL) with normal creatinine (<1.2 mg/dL)
- •Newly diagnosed patient considered a candidate for high-dose chemotherapy and autologous stem cell transplant
- •a. For patients who received one complete cycle of Dara-RVd at MSK, patients can enter treatment at cycle 2 at the discretion of treating investigator and PI
- •Age ≥18 years.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Have adequate organ and hematologic function:
- •Hemoglobin ≥ 7.5 g/dL (prior RBC transfusion or recombinant human erythropoietin use is permitted);
- •Absolute neutrophil count (ANC) ≥ 1.0 x 109/L (G-CSF use is permitted);
- •Platelet count ≥ 75 x 109/L
- •Creatinine Clearance ≥ 30 ml/min. CrCl can be measured or estimated using Cockcroft-Gault method, MDRD, or CKD-EPI formula
- •Total bilirubin ≤ 2 x ULN (≤ 3 x ULN if documented Gilbert's syndrome);
- •AST ≤ 2.5 x ULN;
- •ALT ≤ 2.5 x ULN
- •All study participants must be able to tolerate one of the following thromboprophylaxis strategies: aspirin, low molecular weight heparin or warfarin (coumadin) or alternative anti-coagulant.
- •All study participants must be able to tolerate one of the following thromboprophylaxis strategies: aspirin, low molecular weight heparin or warfarin (Coumadin), or direct-acting oral anticoagulants (DOACs).
- •All study participants must be registered into the mandatory REMS® program and be willing and able to comply with the requirements of REMS®, including compliance with contraception methods (Appendix A).
排除标准
- •Patients who have received > 1 cycle of prior treatment or concurrent systemic therapy for multiple myeloma (excluding corticosteroids or radiation therapy). For patients who received one complete cycle of Dara-RVd at MSK, patients can enter treatment at cycle 2 at the discretion of treating investigator and PI
- •Patients with diagnosis of plasma cell leukemia, primary light chain amyloidosis, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), Waldentröm's macroglobulinemia
- •History of another active primary malignancy within 2 years prior to enrollment, except for adequately treated basal cell carcinoma or squamous cell skin cancer or carcinoma in situ.
- •Significant, uncontrolled comorbid conditions that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in the study. Examples include, but are not limited to
- •Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) < 50% of predicted normal. Note that FEV1 testing is required for participants suspected of having COPD and participants must be excluded if FEV1 is < 50% of predicted normal.
- •Moderate or severe persistent asthma within the past 2 years or uncontrolled asthma of any classification. Note that participants who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate.
- •Infiltrative pulmonary disease
- •Active autoimmune disease requiring systemic immunosuppressive therapy within 6 months before start of study treatment. Exception of vitiligo, type 1 diabetes, and prior autoimmune thyroiditis that is currently euthyroid
- •Disabling psychiatric conditions (e.g., alcohol or drug abuse)., severe dementia, or altered mental status
- •Known history of human immunodeficiency virus (HIV)
- •Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]).
- •i. Subjects with resolved infection (i.e., subjects who are HBsAg negative with antibodies to total hepatitis B core antigen [anti-HBc] with or without the presence of hepatitis B surface antibody [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded.
- •ii. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of HBV vaccination, do not need to be testing for HBV DNA by PCR.
- •h. Seropositive for hepatitis C i. Except in the setting of a sustained virologic response [SVR], defined as a viremia at least 12 weeks after completion of antiviral therapy.
- •i. Clinically significant cardiac disease, including: i. Myocardial infarction within 6 months before enrollment, or unstable or uncontrolled disease/condition related to or affection cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV) ii. Uncontrolled cardiac arrhythmia
- •Pregnant or lactating patients
- •Unwilling to give written, informed consent, unwilling to participate, or unable to comply with the protocol for the duration of the study
研究组 & 干预措施
Phase II, Stage 2
Experimental
The phase II part of the study evaluates MRD negativity (MRD-) rate of alternating Dara-RVd/Tec-RVd after 6 cycles of induction therapy.
干预措施: Dara-RVd (Drug)
Phase II, Stage 2
Experimental
The phase II part of the study evaluates MRD negativity (MRD-) rate of alternating Dara-RVd/Tec-RVd after 6 cycles of induction therapy.
干预措施: Tec-RVd (Drug)
Phase I
Experimental
The phase 1 part of the study evaluates the safety and toxicity of Tec-RVd
干预措施: Dara-RVd (Drug)
Phase I
Experimental
The phase 1 part of the study evaluates the safety and toxicity of Tec-RVd
干预措施: Tec-RVd (Drug)
Phase II, Stage 1
Experimental
The phase II part of the study evaluates MRD negativity (MRD-) rate of alternating Dara-RVd/Tec-RVd after 6 cycles of induction therapy. If 4 or less participants achieve a MRD- after 6 cycles evaluation the trial will be stopped. If 5 or more participants accomplish a MRD- the trial will move on to stage 2
干预措施: Dara-RVd (Drug)
Phase II, Stage 1
Experimental
The phase II part of the study evaluates MRD negativity (MRD-) rate of alternating Dara-RVd/Tec-RVd after 6 cycles of induction therapy. If 4 or less participants achieve a MRD- after 6 cycles evaluation the trial will be stopped. If 5 or more participants accomplish a MRD- the trial will move on to stage 2
干预措施: Tec-RVd (Drug)
结局指标
主要结局
Phase I: Toxicity
时间窗: up to 4 months
Evaluate the safety and toxicity of Tec-RVd for Phase I participants by the number of Dose Limiting Toxicities experienced within the DLT window
Phase II: MRD Negativity
时间窗: up to 6 months
The primary endpoint is MRD negativity (MRD-) rate upon completion of 6 cycles of alternating Dara-RVd with Tec-RVd.
次要结局
未报告次要终点
研究者
研究点 (13)
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