Dose Schedule Study of BCMA Bispecific Antibody, Elranatamab, for Newly Diagnosed Immunoglobulin Light Chain (AL) Amyloidosis

NCT07524634 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: CASE1A26
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is for people who have newly diagnosed with AL (light chain) amyloidosis and have not yet received any treatment for this condition. The purpose of this study is to evaluate whether elranatamab, a type of immunotherapy drug, can produce deep remissions and organ recovery in people with newly diagnosed AL amyloidosis, and to compare two different dosing schedules. Elranatamab (brand name ELREXFIO™) is an investigational (experimental) drug in the setting of AL amyloidosis. It works by connecting immune cells (T-cells) directly to the abnormal plasma cells that are causing amyloidosis, triggering the immune system to destroy those cells. It is not approved by the Food and Drug Administration (FDA) for use in AL amyloidosis. Participants in this study will receive elranatamab as a series of injections under the skin (subcutaneously) over 6 treatment cycles (approximately 6 months). Treatment begins with inpatient "step-up" doses designed to reduce side effects, followed by two different dosing schedules based on which study arm participants are randomly assigned to. Participants will have regular blood tests, physical exams, bone marrow biopsies, and heart assessments throughout the study, and follow-up visits for up to 2 years after treatment ends. This study is randomized, meaning that participants will be assigned by chance (similar to a coin flip) to one of two treatment arms. Participants cannot choose their arm. Participation in this research will last approximately 6 months of active treatment, followed by follow-up visits for up to 2 years (with an option to extend to 5 years).

Conditions

Amyloid Light-chain Amyloidosis

Keywords

B-Cell Maturation Antigen; Elranatamab; Step-up dosing; Bispecific

Outcome Measures

Primary Outcomes (1)

• Efficacy of BCMA bispecific in treating newly diagnosed AL Amyloid, as measured by hematologic complete response (hCR) rates

  hCR rate is defined as the proportion of participants who experience a normalization of free light chain (FLC) levels with negative serume and urine immunofixation, measured through blood tests, at the end of therapy.

  At end of therapy (after 6 cycles, up to 6 months)

Secondary Outcomes (14)

• Time to complete hematologic response (hCR)

  Up to 6 months

• Overall Response rate (ORR)

  At end of therapy (after 6 cycles, up to 6 months)

• Duration of hematologic response

  Up to 6 months

• Progression free survival (PFS) rate

  Up to 60 months

• Overall survival

  Up to 60 months

Study Arms (2)

Arm A: SUD followed by Arm A dose scheduling

EXPERIMENTAL

Participants in Arm A will receive standard step-up dosing (SUD) with one dose a week after SUD, followed by Arm A dose scheduling with a fixed duration of 6 months of BCMA bispecific.

Drug: BCMA bispecific

Arm B: SUD followed by Arm B dose scheduling

EXPERIMENTAL

Participants in Arm B will receive standard step-up dosing (SUD) with one dose a week after SUD, followed by Arm B dose scheduling with a fixed duration of 6 months of BCMA bispecific.

Drug: BCMA bispecific

Interventions

BCMA bispecific DRUG

All Participants will receive standard step-up dosing (SUD) of BCMA bispecific (elranatamab) in Cycle 1. They will then have 5 additional 28-day cycles on two different dose schedules, for a total duration of 6 months.

Also known as: Elranatamab, ELREXFIO™

Arm A: SUD followed by Arm A dose scheduling; Arm B: SUD followed by Arm B dose scheduling

Eligibility Criteria

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

You may qualify if:

• Newly diagnosed Immunoglobulin Light Chain (AL) amyloidosis who have not received any prior therapy.
• Participants must have a tissue biopsy demonstrating Congo red positivity with characteristic birefringence on polarized microscopy and immunohistochemistry or mass spectrometry confirming light chain type.
• Participants must not have any evidence of myeloma defining events based on the International Myeloma Working Group (IMWG) myeloma diagnostic criteria (SLIM-CRAB). This excludes the light chain ratio criteria of involved versus uninvolved free light chains (FLC) over 100 in the absence of CRAB criteria.
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2
• Participants must meet the following organ and marrow function as defined below: Absolute neutrophil count ≥1,000/mcL, Absolute platelet count ≥50,000/mcL, Direct bilirubin ≤1.5 × institutional upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN.
• Participants must have a clonal plasma cell burden of less than 40%.
• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• AL Amyloidosis Cardiac stage I, II or IIIa disease based on the 2015 European Modification of the 2004 Standard Mayo Clinic Staging in participants with advanced cardiac involvement (Dispenzieri et al., 2004; Wechalekar et al., 2013) (NT-proBNP \<8500 ng/L and troponin criteria per staging system).
• The effects of Elranatamab on the developing human fetus are unknown. Based on the mechanism of action, Elranatamab may cause fetal harm when administered to a pregnant woman and therefore should not be used during pregnancy. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and until 90 days since the last dose of Elranatamab. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 90 days after completion of Elranatamab administration.
• Ability to understand and the willingness to sign a written informed consent document.
• Willingness to undergo study procedures, including bone marrow biopsies as detailed in the schedule of events.

You may not qualify if:

• Participants who are receiving any other investigational agents for this condition.
• Participants with Stage IIIB Amyloidosis as defined by the Europeans Revised 2004 Mayo Clinic Criteria.
• Participants with an active malignancy (including lymphoma) with the following exceptions: adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ cervical cancer; adequately treated stage I cancer from which the participant is currently in remission and has been for over 2 years; low-risk prostate cancer with a Gleason score \< 7 and prostate specific antigen \< 10ng/mL; other localized, indolent and/or low risk cancer may be permitted.
• Women who are pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or 4 months following discontinuation of Elranatamab, whichever is longer. Pregnant women are excluded from this study because Elranatamab is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Elranatamab, breastfeeding should be discontinued if the mother is treated with Elranatamab.
• Have any other medical, social or psychological factors that could affect the participant's safety or ability to consent personally or comply with study procedures.
• Participants with active clinically significant autoimmune diseases.
• Participants seropositive for the human immunodeficiency virus (HIV).
• Severe, uncontrolled orthostatic hypotension resulting in syncopal/pre-syncopal events despite optimized medical management (e.g., midodrine, pyridostigmine) and in the absence of volume depletion.
• Plan for autologous stem cell transplant or solid organ transplant during the first 6 months of protocol therapy.
• History of acute coronary syndrome or uncontrolled ventricular arrhythmias within 3 months prior to screening.
• Evidence of Left Ventricular (LV) systolic dysfunction as defined by Left Ventricular Ejection Fraction (LVEF) is \< 30% by echocardiogram at Screening per site cardiology interpretation.
• Have history of sustained ventricular tachycardia or aborted ventricular fibrillation or a history of atrioventricular nodal or sinoatrial nodal dysfunction if a permanent pacemaker (PPM) or implantable cardioverter-defibrillator (ICD) is not placed.
• QT corrected by Fridericia (QTcF) is \> 550 msec on Screening ECG unless they have a PPM/ICD implanted.
• Screening EKG showing acute myocardial ischemia or active conduction system abnormalities with the exception of any of the following: First degree atrioventricular block; Second degree atrioventricular block Type 1 (Mobitz Type 1/Wenckebach type); Right or left bundle branch block (e.g., Left Bundle Branch Block, Right Bundle Branch Block, Left Anterior Fascicular Block, or Left Posterior Fascicular Block); Atrial fibrillation with a controlled ventricular rate; Bifascicular block assessed as benign by the Investigator
• Major surgery that required general anesthesia within 4 weeks of randomization or is planning major surgery during the study.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (2)

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

Case Comprehensive Cancer Center, Cleveland Clinic Foundation Taussig Cancer Institute

Cleveland, Ohio, 44195, United States

Location

Related Publications (4)

• Kastritis, E., et al., Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis. N Engl J Med, 2021. 385(1): p. 46-58.

  BACKGROUND

• Chakraborty, R., et al., Reduced early mortality with Daratumumab-based frontline therapy in AL amyloidosis: A retrospective cohort study. Am J Hematol, 2024. 99(3): p. 477-479.

  BACKGROUND

• Lesokhin, A.M., et al., Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. Nat Med, 2023. 29(9): p. 2259-2267.

  BACKGROUND

• Vianna, P., et al., Safety and efficacy of elranatamab in patients with relapsed and/or refractory immunoglobulin light-chain amyloidosis. Blood, 2025. 146(16): p. 1929-1935.

  BACKGROUND

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Study Officials

• Sandra Mazzoni, DO

  Case Comprehensive Cancer Center, Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sandra Mazzoni, DO

CONTACT

216-444-8111; mazzons@ccf.org

Study Design

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

Study Record Dates

• First Submitted: April 6, 2026
• First Posted: April 13, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): June 1, 2031
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data included in the peer reviewed publication will be publicly available. No raw data will be shared.
• Access Criteria: A peer-reviewed publication will be made available according to the publishing journal's specifications. Cleveland Clinic Foundation personnel will not share study data apart from that which has been published publicly.

Locations

US (2)