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

ConditionsAL AmyloidosisAmyloidosis
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Texas Southwestern Medical Center

About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

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).

Disqualifiers

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).

Trial design

Design model

Sequential

Treatments tested in this trial

  • Belantamab mafodotin 2.5 mg/kg (8 weeks)

    Drug

    2.5 mg/kg IV Belantamab mafodotin IV every 8 weeks 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

  • Belantamab mafodotin 1.4 mg/kg (12 weeks)

    Drug

    1.4 mg/kg Belantamab mafodotin IV every 12 weeks 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

  • 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.

  • Belantamab mafodotin 1.0 mg/kg (12 weeks)

    Drug

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

Treatment groups

37 Participants
are divided into 6 treatment groups

6

Treatment groups

See each treatment group below.

Group A: Cohort (DL 0) for Part 1Experimental treatment 1 intervention
Group B: Cohort (DL +1) for Part 1Experimental treatment 1 intervention
Group C: Cohort (DL -1) for Part 1Experimental treatment 1 intervention
Group D: Cohort (DL -2) for Part 1Experimental treatment 1 intervention
Group E: Cohort Dose Expansion for Part 2Experimental treatment 1 intervention
Group F: Cohort (DL -3) for Part 1Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

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.

Time frame
Up to 24 weeks from Cycle 1 Day 1
2

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.

Time frame
Up to 90 days after completing therapy

Secondary outcomes

1

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

Hematologic responses are assessed as the Overall Response Rate (ORR) which is the percentage of subjects with a confirmed partial response (PR) or better i.e. very good partial response (VGPR), complete hematological response (CHR). The criteria for : i) PR is - Baseline dFLC (difference between iFLC and uninvolved FLC) ≥ 50mg/L: A greater than 50% reduction in the dFLC, Baseline dFLC \< 50 mg/L: ≥ 50% reduction in serum M-protein plus reduction in 24-hr urine M-protein by ≥ 90% or to \<200 mg/24 hours ; ii) Very good partial response is - Baseline dFLC ≥ 50mg/L:Reduction in the dFLC\<40mg/L, Baseline dFLC \< 50 mg/L: ≥ 90% reduction in serum M-protein plus urine M-protein \<100 mg/24 hours ; iii) CHR is - the normalization of free light chain (FLC) levels and ratio, negative serum and urine immunofixation (IFE)

Time frame
Up to 2 years after the last dose
2

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

Hematologic responses are assessed as the Overall Response Rate (ORR) which is the percentage of subjects with a confirmed partial response (PR) or better i.e. very good partial response (VGPR), complete hematological response (CHR). The criteria for : i) PR is - Baseline dFLC (difference between iFLC and uninvolved FLC) ≥ 50mg/L: A greater than 50% reduction in the dFLC, Baseline dFLC \< 50 mg/L: ≥ 50% reduction in serum M-protein plus reduction in 24-hr urine M-protein by ≥ 90% or to \<200 mg/24 hours ; ii) Very good partial response is - Baseline dFLC ≥ 50mg/L:Reduction in the dFLC\<40mg/L, Baseline dFLC \< 50 mg/L: ≥ 90% reduction in serum M-protein plus urine M-protein \<100 mg/24 hours ; iii) CHR is - the normalization of free light chain (FLC) levels and ratio, negative serum and urine immunofixation (IFE)

Time frame
Up to 2 years after the last dose
3

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

Cardiac Response is assessed as Overall Cardiac Response Rate (OcRR) which is the percentage of participants with a confirmed plasma NT-proBNP reduction from baseline of ≥ 30% .

Time frame
Up to 2 years after the last dose
4

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

Non-Cardiac Organ Response (i.e. kidney and/or liver) assessed as: Organ response rate (OrRR) as defined as: 1. Kidney: reduction in proteinuria by ≥ 30% from baseline; or, a reduction in proteinuria \< 0.5g/24 hours without renal progression 2. Liver: 50% decrease in abnormal alkaline phosphatase (ALP) from baseline

Time frame
Up to 2 years after the last dose

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Texas Southwestern Medical Center

Lead sponsor

GlaxoSmithKline

Collaborator

Source ClinicalTrials.gov
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