A Study to Investigate Safety and Clinical Activity of Belantamab Mafodotin in Combination With Lenalidomide, Dexamethasone and Nirogacestat in Patients With Transplant Ineligible Newly Diagnosed Multiple Myeloma

Sponsor
Hellenic Society of Hematology
Study ID
NCT05573802
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

  • Blood Protein Disorders
  • Corneal Disease
  • Gammopathy, Monoclonal
  • Haematologic Disease
  • Multiple Myeloma
  • Neoplasm, Plasma Cell
  • Neoplasms
  • Paraproteinemias

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Belantamab Mafodotin-Blmf — DRUG
    Blmf will be available as 100 mg/vial in single-use vial for reconstitution, supplied as lyophilized powder. Blmf will be delivered as IV solution over at least 30 minutes.
  • Lenalidomide — DRUG
    Lenalidomide will be administered per os.
  • Dexamethasone — DRUG
    Dexamethasone will be administered intravenously or per os.
  • Nirogacestat — DRUG
    Nirogacestat will be administrated each day for all subsequent cycles were Blmf is also administrated.

Study Details

This is a phase 1/2, open-label study designed to assess the safety and clinical activity of different belantamab mafodotin doses in combination with lenalidomide, dexamethasone and nirogacestat in patients with transplant ineligible newly diagnosed multiple myeloma. This will be a 2-part study. In part 1 participants will be enrolled in one cohort to receive belantamab mafodotin in combination with lenalidomide, dexamethasone and nirogacestat and will determine the recommended phase 2 dose (RP2D) to be further evaluated for safety and clinical activity in the dose expansion cohort. The RP2D dose will be used in future studies in the transplant-ineligible newly diagnosed multiple myeloma (NDMM) setting. In the dose expansion phase (Part 2) an expansion cohort will be treated with the RP2D. The expansion cohort will randomize participants (1:1) in two groups to evaluate two alternate dose modification guidelines for corneal AEs. Part 2 of the study will also evaluate an alternative dose modification guideline for corneal adverse events (AEs). Overall, approximately 36 participants will be enrolled in the study. Participant follow-up will continue up to 3 years after the last participant is enrolled (follow-up period range: 3-4 years). The estimated accrual period will be 12 months, corresponding to an approximate total study duration of 4 years.

Key Dates

Start date
Jul 14, 2023
Status verified
Oct 2023
Primary completion
Oct 31, 2026
Completion
Oct 31, 2026

Study Design

Enrollment
36 participants (estimated)
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Part 1 : Dose finding
    Belantamab mafodotin will be administered as a combination therapy as a calculated dose on Day 1 of every other 28-day cycle. Belantamab mafodotin starting dose: • 1.4 mg/kg Q8W (i.e., on Day 1 of every other 28-day cycle) * Dose Level +1: 1.9 mg/kg Q8W * Dose Level -1: 1.0 mg/kg Q8W * Dose Level -2: 1.0 mg/kg Q12W Lenalidomide: 25 mg/d on day 1-21 of every 28-day cycle. Dexamethasone: 40 mg/d on days 1, 8, 15, 22 of every 28-day cycle in participants \< 75 years; 20 mg/d on days 1, 8, 15, 22 of every 28-day cycle in participants ≥ 75 years Nirogacestat: 100 mg twice a day (BID) starting on day -3 and then each day of every other 28-day cycle (i.e., to be given only on cycles where belantamab mafodotin is administered).

Primary Outcome Measure

Part 1: Dose-Limiting Toxicity (DLT) [ Time Frame: Up to 28 days ]

Central Contacts

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