A Study of Dara-RVd and Teclistamab-RVd in People With Multiple Myeloma

Официальное название

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

Обзор

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).

Вмешательства

• Препарат Dara-RVd
  This study is a phase 1/2 study design of alternating 6 cycles of Dara-RVd/Tec-RVd induction therapy
• Препарат Tec-RVd
  This study is a phase 1/2 study design of alternating 6 cycles of Dara-RVd/Tec-RVd induction therapy

Первичные конечные точки

• Phase I: Toxicity [Срок оценки: up to 4 months]
• Phase II: MRD Negativity [Срок оценки: up to 6 months]

Критерии участия

Критерии включения

• 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).

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 7 центров

• Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities) — Basking Ridge
• Memorial Sloan Kettering Monmouth (Limited Protocol Activities) — Middletown
• Memorial Sloan Kettering Bergen (Limited Protocol Activities) — Montvale
• Memorial Sloan Kettering Cancer Center @ Suffolk - Commack (Limited Protocol Activities) — Commack
• Memorial Sloan Kettering Westchester (Limited Protocol Activities) — Harrison
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York
• Memorial Sloan Kettering Nassau (Limited Protocol Activities) — Uniondale

Идентификаторы

NCT: NCT07099391 · 24-288

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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