Measurable Residual Disease-Guided Post-Transplant Elranatamab Maintenance

This study evaluates an individualized approach combining highly active maintenance treatment with elranatamab with peripheral blood-based clonotypic measurable residual disease (MRD) testing in patients with newly diagnosed multiple myeloma. The overall goal is to generate efficacy data for a personalized maintenance approach using bone marrow-based MRD testing (clonoSEQ) to guide post-autologous hematopoietic cell transplant (AHCT) maintenance with elranatamab for this patient population.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Device: clonoSEQ; Drug: Elrantamab

• Study Type: Interventional
• Enrollment (Estimated): 65
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Michael Slade, M.D.; Phone Number: 314-454-8304; Email: sladem@wustl.edu

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Sub-Investigator: Feng Gao, M.D., Ph.D.
      • Sub-Investigator: John F DiPersio, M.D., Ph.D.
      • Sub-Investigator: Ravi Vij, M.D.
      • Sub-Investigator: Li Ding, Ph.D.
      • Contact: Michael Slade, M.D.; Phone Number: 314-454-8304; Email: sladem@wustl.edu
      • Principal Investigator: Michael Slade, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Criteria for Pre-Screening Blood Draw

• Newly diagnosed multiple myeloma (either untreated or receiving first line therapy).
• Potentially eligible for autologous hematopoietic cell transplant (with or without tandem transplant) for frontline therapy.

Inclusion Criteria:

• At least 18 years of age
• Ability to understand and willingness to sign an IRB approved written informed consent document. (Legally authorized representatives may sign and give informed consent on behalf of study participants.)
• Received autologous hematopoietic cell transplantation (with or without tandem transplant) as part of frontline therapy for newly diagnosed IgG or IgA multiple myeloma. Frontline therapy in this setting is defined as treatment received prior to first relapse and may include multiple lines of therapy per the Rajkumar et al definition if treatment changes were made for either toxicity or inadequate response to initial induction.
• Received frontline treatment with at least a triplet regimen including a PI and an IMID (+/- an anti-CD38 antibody)
• Disease response of ≥ partial response (PR) by IMWG criteria at time of study screening (post-transplant).
• MRD-positive on Day 100 landmark assessment (80 to 160 days after AHCT), defined as >1 x 10-5 myeloma cells/cell by clonoSEQ assay (Adaptive Biotechnologies, Seattle, WA) performed on bone marrow aspirate.
• ECOG performance status ≤ 2
• All toxicities from prior treatment should have resolved to Grade ≤ 1 prior to enrollment.

• Adequate bone marrow and organ function within 28 days prior to start of treatment as defined below:

  • Platelets ≥ 75 k/cumm
  • Absolute neutrophil count ≥ 1.0 k/cumm
  • Hemoglobin ≥ 8 g/dL without the use of growth factors or transfusion for at least 2 weeks.
  • Total bilirubin ≤ 2 × upper limit of normal (ULN; ≤ 3 x ULN if documented Gilbert's syndrome)
  • Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 × ULN
  • Creatinine clearance ≥ 30 ml/min.
• The effects of elranatamab on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 5 months after end of treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, or should a man suspect he has fathered a child, s/he must inform her treating physician immediately.

Exclusion Criteria:

• Inability to identify a trackable clonoSEQ ID.
• A history of other malignancy with the exception of non-melanoma skin cancers, low or very low risk prostate cancer by NCCN criteria status post definitive therapy or currently on active surveillance, and malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease. Adjuvant endocrine therapy for hormone receptor-positive breast cancer is not exclusionary.
• Currently receiving any other investigational agents.
• Prior BCMA-based treatment.
• CNS involvement of disease.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to elranatamab or other agents used in the study.
• Uncontrolled intercurrent illness including, but not limited to, plasma cell leukemia, POEMS syndrome, systemic amyloidosis, ongoing or active infection (bacterial, fungal, or viral).
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 28 days prior to first dose of elranatamab.
• HIV-infected if not on effective anti-retroviral therapy with undetectable viral load for 6 months. Patients with HIV who are receiving effective anti-retroviral therapy and have had an undetectable viral load for at least 6 months are eligible. HIV testing not required in the absence of known history of infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Elranatamab; Patients will receive at least 12 months of maintenance elranatamab therapy. Patients will have MRD testing within clonoSEQ every 6 months. If 2 consecutive tests are negative, elranatamab will be stopped and the patient will go on observation schedule. Once a patient starts the observation schedule, standard disease monitoring will be performed every 3 months and bone marrow-based MRD will be performed every 6 months until MRD recurrence, disease progression or end of study period (patients' on-study status will be a maximum of 36 months for treatment and intensive observation combined). Patients who experience MRD recurrence will be re-treated per study protocol. A patient may move back to the observation schedule after treatment re-initiation provided the same criteria as above are met (2 consecutive negative MRD tests). Patients who are determined to have progressive disease per IMWG criteria (whether on treatment or observation schedule) will transition off study.

Device: clonoSEQ; FDA approved MRD testing; Drug: Elrantamab; - Elranatamab will be dosed in 28-day cycles as follows: C1D1: 12 mg SC priming dose; C1D3: 32 mg SC priming dose; C1D8, C1D15, C1D22: 76 mg SC; Cycle 2-Cycle 7: 76 mg SC on D1 and D15; Cycle 8 and subsequent cycles: 76 mg SC on D1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Progression-free survival (PFS) is defined as time to progression or death.	Through completion of follow-up (up to 5 years)
Proportion of patients achieving MRD negativity at the 10^-5 threshold per the clonoSEQ assay		Through completion of end of study visit (up to 36 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to next therapy	Time to next therapy (TTNT) is defined as the time to initiation of subsequent anti-myeloma therapy (excluding standard-of-care maintenance).	Through completion of follow-up (up to 5 years)
Maximum depth of response by IMWG criteria		Through completion of end of study visit (up to 36 months)
Proportion of patients discontinuing therapy per MRD-guided protocol		Through completion of treatment (up to 36 months)
Time on treatment during study period		Through completion of treatment (up to 36 months)
Incidence and severity of treatment-related adverse events by CTCAE v5		From start of treatment through 90 days after completion of treatment (up to 39 months)
Overall survival (OS)	Overall survival (OS) is defined as time to death.	Through completion of follow-up (up to 5 years)
Event-free survival (EFS)	Composite of progression, death, or treatment intolerance (discontinuation due to toxicity)	Through completion of follow-up (up to 5 years)
Proportion of patients achieving sustained MRD-negativity at the 10^-5 threshold per the clonoSEQ assay for at least 12 months	MRD negativity per the clonoSEQ assay will be defined as less than 1 myeloma cell per 10^6 bone marrow cells evaluated (i.e. <10-6)	Through completion of end of study visit (up to 36 months)
Proportion of patients resuming therapy per MRD-guided protocol		Through completion of treatment (up to 36 months)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Pfizer; National Comprehensive Cancer Network
• Investigators: Principal Investigator: Michael Slade, M.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2024
• Primary Completion (Estimated): December 31, 2031
• Study Completion (Estimated): December 31, 2031

Study Registration Dates

• First Submitted: June 25, 2024
• First Submitted That Met QC Criteria: June 25, 2024
• First Posted (Actual): July 3, 2024

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; Maintenance; Stem cell transplant
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma
• Other Study ID Numbers: 202409141

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Access Criteria: Interested parties should contact the investigator to discuss access to de-identified datasets.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No