Tests two drug combinations given in turn for newly diagnosed multiple myeloma

Trial details

Who runs it

Memorial Sloan Kettering Cancer Center

Trial code

NCT07099391

Record updated

2 November 2026

Original description

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).Read full original descriptionShow less

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

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).

Inclusion: 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; 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).

Exclusion: 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; 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]); 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; 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; 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; 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; 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; 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.

ClinicalTrials.gov NCT07099391