Frontline T-cell Engager vs Autologous Stem Cell Transplant (ASCT) and Measurable Residual Disease (MRD)-Guided Sequential Intensification thERapy in Multiple Myeloma

NCT06974786 | Recruiting Phase 2 FDA Drug

• 1 other identifier: MM 195
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 11

Brief Summary

This is an open-label, multi-site, Phase II randomized trial with response-adaptive design for newly diagnosed multiple myeloma (NDMM) participants who have had prior induction therapy. The primary objective of this study is to compare the rates of achieving undetectable measurable residual disease (MRD) in the bone marrow with elranatamab and daratumumab employed as post-induction consolidation and maintenance treatment (Arm A) versus autologous stem cell transplant (ASCT) followed by lenalidomide and daratumumab treatment (Arm B).

Conditions

Multiple Myeloma, Newly Diagnosed; Multiple Myeloma (MM)

Keywords

MM; Newly diagnosed multiple myeloma; NDMM; MRD; ASCT; T-cell engager; Elranatamab; Daratumumab; Lenalidomide

Outcome Measures

Primary Outcomes (1)

• Rate of MRD negativity after completion of Maintenance 1

  Rate of participants with MRD negativity (defined as \<10-5) after completion of the Maintenance 1 portion of the study.

  At 60 weeks

Secondary Outcomes (8)

• Rate of sustained MRD negativity after completion of Consolidation and Maintenance 1 or after completion of Maintenance 1 and Maintenance 2

  60 weeks or 108 weeks, respectively

• Event-free survival (EFS)

  5 years

• Incidence of adverse events

  5 years

• Rate of MRD negativity at any point in Arm A1

  72 weeks and 120 weeks, respectively

• Rate of MRD negativity at any point in Arm B1

  72 weeks and 120 weeks, respectively

Study Arms (4)

Arm A (Elranatamab + Daratumumab)

EXPERIMENTAL

Participants will receive step up dosing of Elranatamab subcutaneously in first cycle followed by weekly dosing for the remainder of the cycle 1. In cycle 2 and 3, elranatamab will be administered every two weeks (Consolidation portion). This will be followed by elranatamab every 4 weeks for 12 cycles in the Maintenance 1 portion. Daratumumab will be given subcutaneously at a fixed dose every 4 weeks starting at Cycle 2 and 3 of Consolidation and for 12 cycles in the Maintenance 1 portion of the study. After completion of Maintenance 1, participants with MRD negativity will receive Elranatamab monotherapy every 4 weeks for additional 12 cycles in Maintenance 2 portion. Participants with MRD positivity will proceed to Arm A1. Participants will undergo therapy in the assigned arm until disease progression, permanent discontinuation (irrespective of reason), death or completion of planned therapy. Cycles will be 28 days. Consolidation consists of 3 cycles; Maintenance 1 consists of 12

Drug: Elranatamab; Drug: Daratumumab

Arm B (ASCT + lenalidomide/daratumumab)

ACTIVE COMPARATOR

Participants will undergo ASCT according to standard of care institutional practices in the Consolidation portion of the study followed by twelve 28-day cycles of Lenalidomide and Daratumumab in the Maintenance 1 portion. After completion of Maintenance 1, participants with MRD negativity will receive Lenalidomide monotherapy for additional 12 cycles in Maintenance 2 portion. Participants with MRD positivity will proceed to Arm B1. Participants will undergo therapy in the assigned arm until disease progression, permanent discontinuation (irrespective of reason), death or completion of planned therapy. Cycles will be 28 days. Consolidation consists of ASCT; Maintenance 1 consists of 12 cycles; Maintenance 2 consists of 12 cycles. Up to 50 participants will be enrolled to this arm.

Drug: Daratumumab; Drug: Lenalidomide; Procedure: autologous stem cell transplantation

Arm A1 (Late Intensification)

EXPERIMENTAL

Participants randomized to Arm A that have MRD positivity after Maintenance 1 will undergo ASCT according to standard of care institutional practices followed by twelve 28-day cycles of maintenance treatment with Lenalidomide and Daratumumab in the Late Intensification portion of the study.

Drug: Daratumumab; Drug: Lenalidomide; Procedure: autologous stem cell transplantation

Arm B1 (Late Intensification)

EXPERIMENTAL

Participants randomized to Arm B that have MRD positivity after Maintenance 1 will receive Elranatamab in combination with Daratumumab for three 28-day cycles as consolidation, followed by Elranatamab in combination with Daratumumab for additional twelve 28-day cycles of maintenance treatment in the Late Intensification portion of the study.

Drug: Elranatamab; Drug: Daratumumab

Interventions

Elranatamab DRUG

Participants will receive step up dosing of Elranatamab subcutaneously in first cycle of consolidation followed by fixed dosing for 2 additional cycles and for 12 cycles in maintenance. Arm A participants will receive additional 12 cycles of Elranatamab monotherapy if they are MRD negative after Maintenance 1 for a total of 27 cycles. Cycles will be 28 days.

Also known as: Elrexfio

Arm A (Elranatamab + Daratumumab); Arm B1 (Late Intensification)

Daratumumab DRUG

Participants will be given 1800 mg of Daratumumab subcutaneously every 4 weeks for up a maximum of 26 cycles.

Also known as: Darzalex

Arm A (Elranatamab + Daratumumab); Arm A1 (Late Intensification); Arm B (ASCT + lenalidomide/daratumumab); Arm B1 (Late Intensification)

Lenalidomide DRUG

Participants will receive 10 mg of Lenalidomide daily by mouth for 21 days of each 28-day cycle for up to a maximum of 24 cycles.

Also known as: Revlimid

Arm A1 (Late Intensification); Arm B (ASCT + lenalidomide/daratumumab)

autologous stem cell transplantation PROCEDURE

Participants will undergo ASCT as standard treatment following individual site's processes and practices.

Also known as: ASCT

Arm A1 (Late Intensification); Arm B (ASCT + lenalidomide/daratumumab)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 years with no upper age limit.
• Newly diagnosed multiple myeloma with indication for initiation of therapy diagnosed within last 12 months. Pretreatment parameters necessary for disease characterization and response assessment must be available.
• Eligible for ASCT according to institutional policy as evaluated by investigator.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Appendix A).
• Prior induction therapy including one PI, lenalidomide, and an anti-CD38 mAb for 16-24 weeks, obtaining at least a partial response (PR).
• Measurable disease meeting at least 1 of the following criteria (at the time of diagnosis):
• a. Serum monoclonal (M) protein ≥1.0 g/dl (≥0.5 g/dl if IgA, IgD, IgE or IgM MM).
• b. ≥200 mg of M protein/24h in the urine. c. Difference between affected and unaffected free light chain ≥10 mg/dL with abnormal kappa to lambda ratio.
• Have trackable clonogenic sequence using ClonoSEQ® (Seattle, WA) identified from a high disease burden sample obtained as SoC and enabling MRD testing during screening phase.
• Have clinical laboratory values meeting the following criteria during the Screening Phase and also at start of administration of study treatment:
• Hemoglobin ≥8g/dL without prior red blood cells (RBC) transfusion within 14 days before the laboratory test; recombinant human erythropoietin use is permitted
• Platelets ≥75,000/µl
• Absolute neutrophil count ≥1,000/µl (prior growth factor support is permitted but must be without support for 7 days for granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating Factor (GM-CSF) and for 14 days for pegylated G-CSF before screening lab test
• Aspartate aminotransferase and alanine aminotransferase ≤2.5 × upper limit of normal (ULN)
• Renal function: Creatinine clearance (CrCl) ≥40 mL/min based on calculation using Cockcroft-Gault formula or measured by a 24-hour urine collection.

You may not qualify if:

• Diagnosis of primary light chain amyloidosis, POEMS, Waldenstrom's macroglobulinemia, plasma cell leukemia, or central nervous system (CNS) involvement by MM.
• Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients (refer to the elranatamab Investigator's Brochure \[IB\] and appropriate package inserts).
• Prior or concurrent exposure to any of the following:
• c. Any anti-BCMA therapy. d. Epigenetic therapy, or treatment with an investigational drug or an invasive investigational medical device within 21 days or ≥5 half-lives, whichever is less.
• e. Investigational vaccine within 4 weeks. f. Live, attenuated vaccine within 4 weeks before randomization. g. Radiotherapy within 14 days. h. Gene-modified adoptive cell therapy (e.g., CAR modified T cells, NK cells). i. Cytotoxic therapy within 14 days.
• Minimum washout period for prior therapy:
• PI therapy - 14 days.
• IMiD agent therapy -14 days.
• Anti CD38 monoclonal therapy - 14 days.
• Corticosteroids - 7 days.
• Known active CNS involvement or exhibits clinical signs of meningeal involvement of MM. If either is suspected, negative whole brain magnetic resonance imaging and lumbar cytology are required.
• Myelodysplastic syndrome or active malignancies (i.e., progressing or requiring treatment change in the last 24 months) other than MM. The only allowed exceptions are:
• a. Non-muscle invasive bladder cancer treated within the last 24 months that is considered completely cured.
• b. Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured.
• c. Non-invasive cervical cancer treated within the last 24 months that is considered completely cured.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Pfizer: collaborator
• coMMit, Myeloma Trials, Innovated: collaborator

Study Sites (11)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

RECRUITING

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Oncology Hematology Care

Cincinnati, Ohio, 45242, United States

RECRUITING

The Ohio State University- The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, 43210, United States

RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

University of Texas Southwestern

Dallas, Texas, 75390, United States

RECRUITING

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

RECRUITING

University of Wisconsin Clinical Science Center

Madison, Wisconsin, 53792, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; Lenalidomide

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

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Henning Schade, MD

  Colorado Blood Cancer Institute

  STUDY CHAIR

Central Study Contacts

Sarah Cannon Development Innovations, LLC

CONTACT

1-844-710-6157; SCRI.InnovationsMedical@scri.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2025
• First Posted: May 16, 2025
• Study Start: August 8, 2025
• Primary Completion (Estimated): November 1, 2032
• Study Completion (Estimated): April 1, 2033
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)