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

NCT06100237 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 20221148
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Minimal Residual Disease (MRD) Negative as Measured by Flow Cytometry

  MRD negative (10\^-5 sensitivity by flow cytometry) as best response by completion of 12 cycles. MRD negative result means no disease is detected after treatment. Status of MRD will be assessed using International Myeloma Working Group (IMWG) Consensus Criteria for Response and Minimal Residual Disease Assessment in Multiple Myeloma, per discretion of treating physician.

  12 months

Secondary Outcomes (12)

• Number of Treatment Related Adverse Events

  Up to 25 months

• Overall Response Rate (ORR)

  Up to 24 months

• Duration of Response (DoR)

  Up to 24 months

• Best Objective Responses (BoR)

  Up to 24 months

• Minimal Residual Disease (MRD) Negativity Rate by Next-Generation Sequencing (NGS)

  Up to 24 months

Study Arms (2)

Cohort A: Tec-Dara

EXPERIMENTAL

Participants will receive the recommended dosage combination treatment Tec-Dara.

Drug: Teclistamab; Drug: Daratumumab SC

Cohort B: Tal-Dara

EXPERIMENTAL

Dosing and treatment schedule for participants in this group will be determined after Cohort A is completed.

Drug: Talquetamab; Drug: Daratumumab SC

Interventions

Teclistamab DRUG

Teclistamab will be administered by subcutaneous (SC) injection per discretion of treating physician. Participants will receive the recommended dosage.

Cohort A: Tec-Dara

Talquetamab DRUG

Talquetamab will be administered per discretion of treating physician. Participants will receive the recommended dosage.

Cohort B: Tal-Dara

Daratumumab SC DRUG

Daratumumab SC will be administered by subcutaneous (SC) injection per discretion of treating physician. Participants will receive the recommended dosage.

Cohort A: Tec-Dara; Cohort B: Tal-Dara

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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).

You may not qualify if:

• 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
• Immunoparesis with reduction of 2 uninvolved immunoglobulin isotypes
• Serum involved/uninvolved free light chain (FLC) ratio ≥8 (but \<100)
• Progressive increase in M-protein level (evolving type of SMM; increase in serum M- protein by ≥25% on 2 successive evaluations within a 6-month period)

Sponsors & Collaborators

• Carl Ola Landgren, MD, PhD: lead
• Janssen Scientific Affairs, LLC: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

talquetamab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Carl O Landgren, MD, PhD

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michelle Armogan

CONTACT

(305) 243-6578; mda182@med.miami.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: October 20, 2023
• First Posted: October 25, 2023
• Study Start: December 4, 2023
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)