Teclistamab in Combination With Daratumumab for High-Risk Smoldering Myeloma: A Clinical and Correlative Phase 2 Immuno-Oncology Study (the REVIVE Study)

Recruiting now · Phase 2

Conditions studied: Multiple Myeloma

In brief

The purpose of this study is to see whether combination treatment of Teclistamab and Daratumumab (Tel-Dara) or combination Talquetamab and Daratumumab (Tal-Dara) will delay the onset of multiple myeloma.

Key facts

Study ID

NCT06100237

Run by

Carl Ola Landgren, MD, PhD

People needed

50

Starts

2023-12-04

Expected to finish

2029-12-31

Last updated by the study team

2026-02-23

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients must have histologically or cytologically confirmed smoldering multiple myeloma (SMM) based on the IMWG Criteria10 including:
• Serum M-protein ≥3 g/dL and/or BMPCs≥10 % (but <60%)
• Absence of anemia: hemoglobin >10 g/dL
• Absence of renal failure: serum creatinine <2.0 mg/dL
• Absence of hypercalcemia: Calcium <10.5 mg/dL
• Absence of lytic bone lesion on X-ray, CT, or positron emission tomography (PET)/CT and not more than 1 lesion on whole body MRI (NOTE: At the discretion of the Investigator, whole body CT or PET/CT may replace MRI in patients who have a contraindication or who are unable to have MRI performed.)
• Involved/uninvolved light chain ratio <100 (unless involved light chain is ≤10 mg/dL) NOTE: Anemia, renal failure, and hypercalcemia is allowed if deemed unrelated to multiple myeloma (MM), see organ function criteria in point #5 below.
• Patients must have measurable disease within the past 4 weeks, which is defined by any one of the following:
• Serum monoclonal protein ≥ 0.5 g/dL
• Urine monoclonal protein >200 mg/24 hour
• Serum immunoglobulin free light chain ≥10 mg/dL AND abnormal kappa/lambda serum free light chain ratio (reference: 0.26-1.65)
• Other measurable disease as defined by the International Myeloma Working Group (IMWG).
• Because the primary endpoint is MRD negativity based on bone marrow analysis, a patient without measurable disease in blood or urine may be enrolled and assessed for MRD negativity. NOTE: In patients who received minimal prior therapy within the allowable range per exclusion criteria 1, patients should have had documented measurable disease within 4 weeks of starting that respective therapy if currently unmeasurable.
• Patients age ≥18 years.
• Patients with Eastern Cooperative Oncology Group (ECOG) performance status 0-1 assessed within the past 45 days. (See Appendix 17.1).
• Patients must have adequate organ and marrow function ≤45 days as defined below:
• Absolute neutrophil count (ANC) >1.0 K cells/μL; At the discretion of the Investigator, patients with an ANC of 0.5 K/μL-1.0 K/μL may also be enrolled if clinically appropriate (eg, patients with a baseline neutropenia that is chronic and/or ethnic neutropenia and that does not cause complications, e.g, no history of chronic infections).
• Platelet count >75 K cells/μL
• Hemoglobin >8 g/dL (transfusions are permissible if the cause of the anemia is other than myeloma)
• Total bilirubin <1.5 X upper limit of normal (ULN). NOTE: Isolated total bilirubin ≥1.5 X ULN with conjugated [direct] bilirubin <1.5 X ULN is allowed for those participants with known Gilbert's syndrome.
• Aspartate aminotransferase (AST)/ alanine transaminase (ALT) ≤2.5 X ULN
• ≥30 mL/min based on Modification of Diet in Renal Disease (MDRD) 4-variable Formula calculation (Appendix 17.2) or creatine clearance (CrCl) measured by a 24-hour urine collection. The estimated glomerular filtration rate (eGFR) may also be determined by using other widely accepted methods as clinically indicated, ie, Cockcroft-Gault method or the chronic kidney disease (CKD)-epidemiology collaboration (EPI) per institutional standards.
• Patients must have SMM that is categorized as high-risk for progression to MM-related end- organ damage by both clinical and genomic characteristics. Patients may be categorized as high risk by the Program for Study and Treatment of Malignant Hemopathies (PETHEMA) (immunoparesis and ≥95% aberrant bone marrow plasma cells (aBMPCs) by flow) and/or Mayo Clinic78 (20/2/20) criteria and/or have clonal BMPCs ≥10% with any one or more of the following criteria4:
• Serum M protein ≥3 g/dL
• Immunoglobulin A (IgA) SMM

You may not qualify if…

• Patients who have received prior systemic therapies for SMM/MM. One prior cycle (4-5 weeks) of therapy for SMM is allowed provided that patient undergoes a 4-week washout period prior to first dose of study treatment. Treatment with corticosteroids for other indications is permitted.
• Patients who are receiving any other investigational agents for any reasons.
• Patients who receive a live attenuated vaccine within 4 weeks of scheduled study treatment administration.
• Contraindication to any concomitant medication, including those medications administered for infusion reaction, antiviral, antibacterial, anticoagulation, tumor lysis, or hydration prophylaxis given prior to therapy.
• Patient has any of the following:
• Human immunodeficiency virus (HIV)-positive with 1 or more of the following:
• History of acquired immune deficiency syndrome (AIDS)-defining conditions cluster of differentiation (CD4)count <350 cells/mm3
• Detectable viral load during screening or within 6 months prior to screening
• Not receiving highly active anti-retroviral therapy
• Had a change in antiretroviral therapy within 6 months of the start of screening
• Receiving antiretroviral therapy that may interfere with study treatment as assessed after discussion with the Medical Monitor
• Hepatitis B infection (ie, hepatitis B surface antigen (HBsAg) or hepatitis B virus (HBV)- DNA positive). Patients with resolved infection (ie, patients who are HBsAg negative but positive for antibodies to hepatitis B core antigen (anti-HBc) and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of HBV DNA levels. Those who are PCR positive will be excluded. In the event the infection status is unclear, quantitative viral levels are necessary to determine the infection status; see Section 10.3.5.2.1 for further required assessments.
• EXCEPTION: Participants with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination do not need to be tested for HBV DNA by PCR.
• Active hepatitis C infection as measured by positive HCV-ribonucleic acid (RNA) testing.
• Participants with a history of hepatitis C virus (HCV) antibody positivity must undergo HCV-RNA testing (Section 10.3.5.2.2). If a participant with history of chronic hepatitis C infection (defined as both HCV antibody and HCV-RNA positive) completed antiviral therapy and has undetectable HCV-RNA 12 weeks following the completion of therapy, the participant is eligible for the study.
• 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 with known or suspected of having COPD or asthma, and participants must be excluded if FEV1 <50% of predicted normal.
• Moderate or severe persistent asthma within the past 2 years or uncontrolled asthma of any classification. Note that FEV1 testing is required for participants with known or suspected asthma, and participants must be excluded if FEV1 <50% of predicted normal.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the experimental agents used in study.
• Female patient refuses to discontinue breastfeeding her infant during study treatment or within 5 months after receiving the last dose of study treatment.
• Participant plans to father a child while enrolled in this study or within 3 months after the last dose of study treatment.
• Presence of the following cardiac conditions:
• New York Heart Association stage III or IV congestive heart failure
• Myocardial infarction or coronary artery bypass graft ≤6 months prior to study enrollment
• History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration
• Uncontrolled cardiac arrhythmia or clinically significant electrocardiogram (ECG) abnormalities

Where it is running

• University of Miami — Miami, Florida, United States (enrolling)

Full record on ClinicalTrials.gov

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