Blmf, Lenalidomide and Dexamethasone in Transplant-ineligible Patients With Newly Diagnosed Multiple Myeloma

NCT04808037 | Active Not Recruiting Phase 1

• 1 other identifier: EAE-2020/MM0107
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

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 and dexamethasone.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (4)

• Number of participants with dose-limiting toxicities (DLTs) in each of the cohorts 1-3

  Determination of the safety and tolerability of belantamab mafodotin in combination with lenalidomide and dexamethasone to establish a recommended Phase 2 dose for participants with newly diagnosed Multiple Myeloma, transplant-ineligible

  Five (5) years after last participant randomization

• Overall Response rate as per IMWG by Investigator Assessment, defined as the percentage of participants with a confirmed PR, VGPR, CR or sCR

  Evaluation of the preliminary clinical activity of the Recommended Phase 2 Dose of belantamab mafodotin in combination with lenalidomide and dexamethasone for participants with newly diagnosed Multiple Myeloma, transplant-ineligible

  Five (5) years after last participant randomization

• Number of participants with adverse events (AEs) and serious adverse events (SAEs) in each of the cohorts 1-3

  Determine the safety and tolerability of blmf in combination with lenalidomide and dexamethasone to establish a recommended Phase 2 dose for participants with newly diagnosed Multiple Myeloma, transplant-ineligible

  Five (5) years after last participant randomization

• Number of participants with adverse events (AEs) and serious adverse events (SAEs) in patients receiving the Recommended Phase 2 Dose

  Further evaluation of the safety of Belantamab Mafodotin in combination with Lenalidomide and Dexamethasone

  Five (5) years after last participant randomization

Study Arms (5)

Cohort 1, First Part

EXPERIMENTAL

12 patients are anticipated to receive Belantamab Mafodotin 2.5 Q8W = 2.5 mg/kg on Day 1 of every other 28-day cycle, in combination with Lenalidomide and Dexamethasone

Drug: Belantamab mafodotin

Cohort 2, First Part

EXPERIMENTAL

12 patients are anticipated to receive Belantamab Mafodotin 1.9 Q8W = 1.9 mg/kg on Day 1 of every other 28-day cycle, in combination with Lenalidomide and Dexamethasone

Drug: Belantamab mafodotin

Cohort 3, First Part

EXPERIMENTAL

12 patients are anticipated to receive Belantamab Mafodotin 1.4 Q8W = 1.4 mg/kg on Day 1 of every other 28-day cycle, in combination with Lenalidomide and Dexamethasone

Drug: Belantamab mafodotin

Group A, Second Part

EXPERIMENTAL

15 patients are anticipated to receive Belantamab Mafodotin in the Recommended Phase 2 Dose, in combination with Lenalidomide and Dexamethasone. In this Arm the ocular toxicity will be graded according to the Dose Modification Guidelines for Corneal-Related Adverse Events Associated with belantamab mafodotin

Drug: Belantamab mafodotin

Group B, Second Part

EXPERIMENTAL

15 patients are anticipated to receive Belantamab Mafodotin in the Recommended Phase 2 Dose, in combination with Lenalidomide and Dexamethasone. In this Arm the ocular toxicity will be graded according to the Dose modification guidance based on visual acuity

Drug: Belantamab mafodotin

Interventions

Belantamab mafodotin DRUG

Belantamab mafodotin in combination with Lenalidomide and Dexamethasone in patients with newly diagnosed Multiple Myeloma transplant-ineligible

Also known as: Blenrep

Cohort 1, First Part; Cohort 2, First Part; Cohort 3, First Part; Group A, Second Part; Group B, Second Part

Eligibility Criteria

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

You may qualify if:

• Participant at least 18 years of age
• Monoclonal plasma cells in the bone marrow ≥10% or presence of a biopsy proven plasmacytoma and documented multiple myeloma satisfying at least one of the calcium, renal, anemia, bone (CRAB) criteria or biomarkers of malignancy criteria:
• CRAB criteria:
• i. Hypercalcemia: serum calcium \>0.25 mmol/L (\>1 mg/dL) higher than upper limit of normal (ULN) or \>2.75 mmol/L (\>11 mg/dL).
• ii. Renal insufficiency: creatinine clearance \<40mL/min or serum creatinine \>177 μmol/L (\>2 mg/dL).
• iii. Anemia: hemoglobin \>2 g/dL below the lower limit of normal or hemoglobin \<10 g/dL.
• iv. Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT.
• Biomarkers of Malignancy:
• Clonal bone marrow plasma cell percentage ≥60%.
• Involved: uninvolved serum FLC ratio ≥100.
• \>1 focal lesion on magnetic resonance imaging (MRI) studies.
• Must have at least ONE aspect of measurable disease, defined as one of the following:
• Urine M-protein excretion ≥200 mg/24 hrs (≥0.2g/24 hrs), or
• Serum M-protein concentration ≥0.5 g/dL (≥5.0 g/L), or
• Serum free light chain (FLC) assay: involved FLC level ≥10 mg/dL (≥100 mg/L) and an abnormal serum free light chain ratio (\<0.26 or \>1.65).

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Prior systemic therapy for multiple myeloma, or SMM.
• NOTE 1: An emergency course of steroids (defined as no greater than 40 mg of dexamethasone, or equivalent per day for a maximum of 4 days (that is, a total of 160 mg) is permitted.
• NOTE 2: Focal palliative radiation is permitted prior to enrollment, provided that it occurred at least 2 weeks prior to the first dose of study drug, that the participant has recovered from radiation-related toxicities, and that the participant did not require corticosteroid administration (for a longer period than that specified in NOTE 1 above) for radiation-induced adverse events
• Participant is eligible for high dose chemotherapy with ASCT, as determined by a frailty score of 0 as assessed by the IMWG frailty index (1).
• Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the NCI CTCAE Version 5.
• Major surgery within 4 weeks prior to the first dose of study drug.
• Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including lab abnormalities) that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures.
• Evidence of active mucosal or internal bleeding uncontrolled by local therapy and not explained by reversible coagulopathy.
• Current active liver or biliary disease (except for Gilbert's syndrome or asymptomatic gallstones, or otherwise stable chronic liver disease as per the Investigator's assessment).
• Participants with previous or concurrent malignancies other than multiple myeloma are excluded. Exceptions are surgically treated cervical carcinoma in situ, or any other malignancy that has been considered medically stable for at least 2 years. The participant must not be receiving active therapy, other than hormonal therapy for this disease.
• o Note: Participants with curatively treated non-melanoma skin cancer are allowed without a 2-year restriction.
• Evidence of cardiovascular risk including any of the following:
• Evidence of current clinically significant untreated arrhythmias, including clinically significant ECG abnormalities, second degree (Mobitz Type II) or third degree atrioventricular (AV) block.
• History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening.

Sponsors & Collaborators

• Hellenic Society of Hematology: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

General Hospital of Athens "Alexandra"

Athens, Attica, 11528, Greece

Location

Related Publications (1)

• Gavriatopoulou M, Ntanasis-Stathopoulos I, Malandrakis P, Fotiou D, Migkou M, Theodorakakou F, Spiliopoulou V, Kanellias N, Eleutherakis-Papaiakovou E, Roussou M, Psarros G, Kastritis E, Dimopoulos MA, Terpos E. Belantamab mafodotin, lenalidomide, and dexamethasone in transplant-ineligible patients with newly diagnosed multiple myeloma: Analysis of belantamab mafodotin-associated ocular adverse events and their impact on daily functioning from the part 1 of a phase 1/2 study. Am J Hematol. 2024 Mar;99(3):502-504. doi: 10.1002/ajh.27219. Epub 2024 Jan 25. No abstract available.

  PMID: 38270219 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

belantamab mafodotin

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Meletios-Athanasios Dimopoulos

  National and Kapodistrian University of Athens School of Medicine, Athens - Greece

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2021
• First Posted: March 19, 2021
• Study Start: February 22, 2021
• Primary Completion (Estimated): September 8, 2028
• Study Completion (Estimated): November 8, 2028
• Last Updated: October 24, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)