Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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 Design

Phase
Phase 2
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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.
  • 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
  • Device: clonoSEQ
    FDA approved MRD testing

Recruiting Locations

Washington University in St. Louis and nearby locations

Washington University School of Medicine
St Louis 4407066, Missouri 4398678 63110
Contact:
Michael Slade, M.D.
314-454-8304
sladem@wustl.edu

More Details

NCT ID
NCT06483100
Status
Recruiting
Sponsor
Washington University School of Medicine

Study Contact

Michael Slade, M.D.
314-454-8304
sladem@wustl.edu

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.