Phase 1/2a Study of Belantamab Mafodotin in Relapsed or Refractory AL Amyloidosis

NCT05145816 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: SCCC-06A21; STU-2021-0952
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this study is to test the safety of drug, Belantamab Mafodotin, and see what effects (good and bad) it has on people who take it and have amyloidosis, and to determine the most effective dose of the drug. The study will have 2 phases (parts). The first phase of the study will test different doses of Belantamab Mafodotin. The second phase will test Belantamab Mafodotin at the dose level found to be safe and effective in phase 1

Conditions

AL Amyloidosis; Amyloidosis

Outcome Measures

Primary Outcomes (2)

• Safety/Tolerability as measured by number of subjects with dose limiting toxicity (Part 1)

  Safety/Tolerability is measured by the number of participants treated with different dose level of belantamab mafodotin who experience dose limiting toxicity adverse events (AE) \>= Grade 3, as defined by Common Terminology Criteria for Adverse Events by CTCAE v5.0 for Part 1.

  Up to 24 weeks from Cycle 1 Day 1

• Safety/Tolerability at the recommended Phase II dose of Belantamab Mafodotin, as measured by number of subjects with dose limiting toxicity (Part 2)

  Safety/Tolerability at the recommended Phase II dose of Belantamab Mafodotin is measured by the number of subjects who experience dose limiting toxicities (\>= Grade 3, as defined by Common Terminology Criteria for Adverse Events by CTCAE v5.0) and cardiac and ocular AEs.

  Up to 90 days after completing therapy

Secondary Outcomes (12)

• Percentage of subjects with preliminary hematological responses associated with Belantamab mafodotin (Part 1)

  Up to 2 years after the last dose

• Percentage of subjects with preliminary hematological responses associated with Belantamab mafodotin (Part 2)

  Up to 2 years after the last dose

• Percentage of subjects with cardiac response associated with Belantamab mafodotin (Part 2)

  Up to 2 years after the last dose

• Percentage of subjects with non-cardiac organ response associated with Belantamab mafodotin (Part 2)

  Up to 2 years after the last dose

• Percentage of participants with Complete Hematological Response (CHR) (Part 2)

  Up to 2 years after the last dose

Study Arms (6)

Cohort (DL 0) for Part 1

EXPERIMENTAL

Cohort (DL 0) for Starting Dose : 1.9 mg/kg Belantamab mafodotin intravenously every 8 weeks

Drug: Belantamab mafodotin 1.9 mg/kg (8 weeks)

Cohort (DL +1) for Part 1

EXPERIMENTAL

Cohort (DL +1) for Dose Escalation: 2.5 mg/kg Belantamab mafodotin intravenously every 8 weeks

Drug: Belantamab mafodotin 2.5 mg/kg (8 weeks)

Cohort (DL -1) for Part 1

EXPERIMENTAL

Cohort (DL -1) for Dose De-escalation : 1.9 mg/kg Belantamab mafodotin intravenously every 12 weeks

Drug: Belantamab mafodotin 1.9 mg/kg (12 weeks)

Cohort (DL -2) for Part 1

EXPERIMENTAL

Cohort (DL -2) for Dose De-escalation: 1.4 mg/kg Belantamab mafodotin intravenously every 12 weeks

Drug: Belantamab mafodotin 1.4 mg/kg (12 weeks)

Cohort Dose Expansion for Part 2

EXPERIMENTAL

Cohort Dose expansion for Part 2: Belantamab mafodotin Dose from1.0 mg/kg to 2.5mg/kg every 8 or 12 weeks as determined by Part 1 recommended dosage calculations.

Drug: Belantamab mafodotin every 8 weeks or 12 weeks as determined by Part 1 recommended dosages

Cohort (DL -3) for Part 1

EXPERIMENTAL

Cohort (DL -3) for Dose De-escalation: 1.0 mg/kg Belantamab mafodotin intravenously every 12 weeks

Drug: Belantamab mafodotin 1.0 mg/kg (12 weeks)

Interventions

Belantamab mafodotin 1.4 mg/kg (12 weeks) DRUG

1.4 mg/kg Belantamab mafodotin IV every 12 weeks for Part 1

Cohort (DL -2) for Part 1

Belantamab mafodotin 1.9 mg/kg (12 weeks) DRUG

1.9 mg/kg Belantamab mafodotin IV every 12 weeks for Part 1

Cohort (DL -1) for Part 1

Belantamab mafodotin 1.0 mg/kg (12 weeks) DRUG

1.0 mg/kg Belantamab mafodotin IV every 12 weeks for Part 1

Cohort (DL -3) for Part 1

Belantamab mafodotin 2.5 mg/kg (8 weeks) DRUG

2.5 mg/kg IV Belantamab mafodotin IV every 8 weeks for Part 1

Cohort (DL +1) for Part 1

Belantamab mafodotin 1.9 mg/kg (8 weeks) DRUG

1.9 mg/kg IV Belantamab mafodotin IV every 8weeks for Part 1

Cohort (DL 0) for Part 1

Belantamab mafodotin every 8 weeks or 12 weeks as determined by Part 1 recommended dosages DRUG

Belantamab mafodotin Dose 1.0 mg/kg, 1.4 mg/kg, 1.9mg/kg or 2.5mg/kg every 8 weeks or 12 weeks as determined by Part 1 recommended dosages.

Cohort Dose Expansion for Part 2

Eligibility Criteria

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

You may qualify if:

• Participants medically diagnosed with relapsed or refractory Amyloid Light Chain Amyloidosis (AL amyloidosis) with one or more line of treatment as below:
• Must have received a proteosome inhibitor, alkylator and anti-cluster of differentiation 38 (CD38) antibody (e.g., daratumumab - for patients who were eligible to receive in newly diagnosed AL Amyloidosis) and autologous stem cell transplant (for transplant eligible candidates).
• Failed treatment and/or intolerant/ineligible for above agents
• NOTE: Patients who fail to achieve Partial Hematological Response or better after 2 cycles of induction therapy for newly diagnosed AL Amyloidosis are also eligible.
• Participant must be over 18 years of age inclusive, at the time of signing the informed consent.
• Participant and Disease Characteristics: Patient must have primary systemic AL amyloidosis, histologically confirmed at the initial diagnosis before initiation of 1st-line treatment by positive Congo red stain with green birefringence on polarized light microscopy, Or characteristic appearance by electron microscopy AND confirmatory AL amyloid typing (mass spectrometry-based proteomic analysis or immunofluorescence).
• Patient must have measurable disease within 28 days prior to registration; serum quantitative immunoglobulins (immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM), serum free kappa and lambda, and serum protein electrophoresis (SPEP) with M-protein quantification must be obtained within 14 days prior to registration.
• Measurable disease of amyloid light chain amyloidosis as defined by at least One of the following:
• a. Serum M-protein ≥0.5 g/dL by protein electrophoresis (routine serum protein electrophoresis and immunofixation).
• b. Serum free light chain ≥50 mg/L with an abnormal kappa: lambda ratio or the difference between the involved and uninvolved free light chains (dFLC) ≥50 mg/L.
• One or more organs impacted by AL Amyloidosis according to consensus guidelines below per National Comprehensive Cancer Network (NCCN)Guidelines Version 1.2016:
• a. Cardiac Involvement i. Mean left ventricular wall thickness on echocardiogram greater than or equal to 12 mm in the absence of hypertension or valvular heart disease, OR N-terminal fragment brain natriuretic protein (NT-pro) brain natriuretic peptide (BNP) greater than 332 ng/mL provided that patient does not have impaired renal function (as defined by calculated creatinine clearance less than 25 mL/min) within 14 days prior to registration, OR prior cardiac biopsy (at time of diagnosis) showing amyloid deposition with past documented or presently noted clinical symptoms and signs supportive of a diagnosis of heart failure in the absence of an alternative explanation for heart failure.
• b. Non-Cardiac Organ Involvement
• i. Kidney: albuminuria greater than or equal to 500 mg per day on a 24-hour urine specimen within 35 days prior to registration, OR prior kidney biopsy (at the time of diagnosis) showing amyloid deposition.
• ii. Liver: hepatomegaly (total liver span \> 15 cm) as demonstrated by computed tomography (CT) or magnetic resonance imaging (MRI) within 35 days prior to registration OR alkaline phosphatase (ALP) greater than 1.5 times the institutional upper limit of normal within 14 days prior to registration, OR prior liver biopsy (at the time of diagnosis) showing amyloid deposition.

You may not qualify if:

• Patients previously treated for active symptomatic multiple myeloma.
• Any corneal disease except for mild epithelial punctate keratopathy.
• Patients with known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to belantamab mafodotin or drugs chemically related to belantamab mafodotin, or any of the components of the study treatment.
• Patients eligible for autologous stem cell transplantation (ASCT).
• Evidence of significant cardiovascular condition as specified below:
• N-terminal-prohormone of brain natriuretic peptide (NT-proBNP) ≥ 8500ng/L within 14 days of registration.
• New York Heart Association (NYHA) classification IIIB (3b) through IV (4) heart failure
• Heart failure that in the opinion of the investigator is on the basis of ischemic heart disease (e.g., prior myocardial infarction with documented history of cardiac enzyme elevation and electrocardiogram (ECG) changes) or uncorrected valvular disease and not primarily due to AL amyloid cardiomyopathy
• Unstable heart failure defined as emergency hospitalization for worsening, or decompensated heart failure, or syncopal episode within 1 month of screening
• Subjects with a history of sustained ventricular tachycardia or aborted ventricular fibrillation or with a history of atrioventricular nodal or sinoatrial (SA) nodal dysfunction for which a pacemaker/implantable cardioverter-defibrillator (ICD) is indicated but not placed (Subjects who do have a pacemaker/ICD are allowed on study)
• Interval from the Q wave on the ECG to point T using Fredericia's formula (QTcF) \> 500 msec. Subjects who have a pacemaker may be included regardless of calculated QTc interval
• Symptomatic, clinically significant autonomic neuropathy which the Investigator feels will preclude administration of study treatment
• Acute coronary syndrome, or any form of coronary revascularization procedure including coronary artery bypass grafting (CABG), within 6 months of screening
• Prior solid organ transplant, or anticipated to undergo solid organ transplantation, or requiring left ventricular assist device (LVAD) implantation, during the course of the study
• Stroke within 6 months of screening, or transient ischemic attack (TIA) within 3 months of screening

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• GlaxoSmithKline: collaborator

Study Sites (3)

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, 37232, United States

NOT YET RECRUITING

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, 84112, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis; Amyloidosis

Interventions

belantamab mafodotin

Condition Hierarchy (Ancestors)

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

Study Officials

• Larry Anderson, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Donglan Xia

CONTACT

214-648-7097; Donglan.Xia@UTSouthwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: This is an open-label, dose-escalation trial consisting of two parts: a Part 1 dose escalation phase and a Part 2 cohort expansion phase for safety and clinical activity testing.

Study Record Dates

• First Submitted: November 23, 2021
• First Posted: December 6, 2021
• Study Start: February 15, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: May 7, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)