Belantamab Mafodotin in Newly Diagnosed Transplant Eligible Multiple Myeloma Patients

NCT04802356 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: GEM-BELA-VRd2020-002050-24
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 12

Brief Summary

This is a multicenter, open label clinical trial evaluating the safety of the combination of belantamab mafodotin + the combination treatment VRd (bortezomib, lenalidomide, dexamethasone) in newly diagnosed (ND) transplant eligible multiple myeloma (MM) patients. Eligible patients will be included in the study and they will receive three induction cycles with belantamab mafodotin (8-week cycles) and six induction cycles with VRd (4-week cycles). Immediately after the fourth VRd cycle, and in the absence of progression or unacceptable toxicity, mobilization of hematopoietic stem cells with G-CSF and subsequent apheresis will take place. Then, patients will receive one additional induction cycle with belantamab mafodotin (8-week cycle) and two additional induction cycles with VRd (4-week cycles) followed by intensification with high-dose melphalan (200mg/m2) and the autologous stem cell transplant. Three months after transplantation, and as long as clinical and hematological conditions allow, patients will receive one cycle of consolidation with belantamab mafodotin (8-week cycle) and two additional cycles of consolidation with VRd (4-week cycles) at the same doses as during induction and, subsequently, patients will receive maintenance treatment with lenalidomide (continuously until disease progression, patient withdrawal, unacceptable toxicity, loss to follow up, end of study or death) and belantamab mafodotin (for 2 years).

Conditions

Multiple Myeloma

Keywords

NEWLY DIAGNOSED; TRANSPLANT ELEGIBLE; BELANTAMAB MAFODOTIN

Outcome Measures

Primary Outcomes (4)

• Incidence of deaths

  Number of patients that are exitus after start of the study treatment

  Throughout the study period. Approximately 48 months

• Incidence of adverse events (AEs)

  Number of patients experiencing AEs, either treatment or non-treatment related, classified according to severity and graded according to NCTCAE V4.0

  Throughout the study period. Approximately 48 months

• Incidence of analytical alterations

  Changes in laboratory analytes from the hematology and blood chemistry panel after start of the study experimental treatment

  Throughout the study period. Approximately 48 months

• Incidence of ocular events

  Number of patients experiencing ocular alterations after start of the study experimental treatment.

  Throughout the study period. Approximately 48 months

Secondary Outcomes (9)

• Overall Response Rate (ORR)

  Throughout the study period. Approximately 48 months

• Complete Response Rate (CRR)

  Throughout the study period. Approximately 48 months

• Minimal Residual Disease (MRD) negativity rate

  Throughout the study period. Approximately 48 months

• Time to Response (TTR)

  Throughout the study period. Approximately 48 months

• Duration of Response (DoR)

  Throughout the study period. Approximately 48 months

Study Arms (1)

Multiple Myeloma experimental arm

EXPERIMENTAL

Combination of belantamab mafodotin + the combination treatment VRd (bortezomib, lenalidomide, dexamethasone)

Drug: Belantamab mafodotin; Drug: Bortezomib; Drug: Lenalidomide; Drug: Dexamethasone; Procedure: Autologous stem cell transplant (ASCT)

Interventions

Belantamab mafodotin DRUG

Dose of 2.5 mg/kg/every 8 weeks on day 1, intravenously, Induction: three induction cycles with belantamab mafodotin in combination with VRd. Consolidation: one cycle after 90 days of transplantation with belantamab mafodotin in combination with VRd. Maintenance: belantamab mafodotin in combination with lenalidomide until disease progression, patients withdrawal, death or up to two years, whichever occurs first

Also known as: Blenrep

Multiple Myeloma experimental arm

Bortezomib DRUG

Dose of 1.3 mg/m2, on days: 1, 4, 8 and 11 of every 28-day cycle. Subcutaneous administration Induction: 6 cycles Consolidation: 2 cycles

Multiple Myeloma experimental arm

Lenalidomide DRUG

Dose of 25 mg/day on days 1-21 of every 28-day cycle. Oral administration. Induction: 6 cycles Consolidation: 2 cycles Maintenance: 10 mg/day on days 1-21 continuously (may increase up to 15 mg/day) until disease progression, patients withdrawal, death, whichever occurs first

Multiple Myeloma experimental arm

Dexamethasone DRUG

Dose of 20 mg on days: 1, 2, 4, 5, 8, 9, 11 and 12 of every 28-day cycle. Oral administration Induction: 6 cycles Consolidation: 2 cycles

Multiple Myeloma experimental arm

Autologous stem cell transplant (ASCT) PROCEDURE

High-dose melphalan (200 mg/m2) and ASCT will be performed as per routine practice

Multiple Myeloma experimental arm

Eligibility Criteria

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

You may qualify if:

• Participant must have Newly diagnosed multiple myeloma. Newly diagnosed subjects must have symptomatic disease following the IMWG updated criteria (Rajkumar Lancet 2014, Appendix 6).
• Participant must have a measurable secretory disease defined as either serum monoclonal protein of ≥ 0,5 g/dl or urine monoclonal (light chain) protein ≥ 200mg/24h.For patients whose disease is only measurable by serum FLC, the involved FLC should be ≥ 10mg/L (100 mg/dl), with an abnormal serum FLC ratio.
• Newly diagnosed participants must be eligible for stem cell transplant at investigator criteria.
• Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Participant must be ≥ 18 years of age
• Participant must have adequate organ function, defined as follows:
• System Laboratory Values Hematologic Absolute neutrophil count (ANC) ≥1.5 X 109/L Hemoglobin ≥8.0 g/dL Platelets ≥75 x 109/L for subjects in whom \<50% of bone marrow nucleated cells are plasma cells; otherwise platelet count \>50 × 109/L Calcium corrected serum calcium \<14 mg/dL (\<3.5 mmol/L); or free ionized calcium \<6.5 mg/dL (\<1.6 mmol/L); Hepatic Total bilirubin ≤1.5X ULN (Isolated bilirubin ≥1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%) ALT ≤2.5 X ULN AST ≤2.5 X ULN Renal eGFRa ≥30 mL/min/ 1.73 m2 Spot urine (albumin/creatinine ratios (spot urine) \<500 mg/g (56 mg/mmol)
• Female participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
• Is not a woman of childbearing potential (WOCBP) OR
• Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), preferably with low user dependency, during the intervention period and for at least 4 months after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
• Nonchildbearing potential is defined as follows (by other than medical reasons):
• ≥45 years of age and has not had menses for \>1 year
• Patients who have been amenorrhoeic for \<2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure.
• Male participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

You may not qualify if:

• Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), plasma cell leukemia or active POEMS syndrome at the time of screening.
• Participant has malignancies other than disease under study, except for any other malignancy from which the participant has been disease-free for more than 2 years and, in the opinion of the principal investigators, will not affect the evaluation of the effects of this clinical trial treatment on the currently targeted malignancy. Participants with curatively treated non-melanoma skin cancer may be enrolled.
• Participant has meningeal involvement of multiple myeloma.
• Pregnant or breastfeeding females.
• Participant is simultaneously enrolled in other interventional clinical trial.
• Participant must has used an investigational drug within 14 days or five half-lives, whichever is shorter, preceding the first dose of study drug.
• Participant has used of any anti-myeloma drug therapy, except for steroid pulses in case of emergency (40 mg of dexamethasone for 4 days), the administration of bisphosphonates or antialgic radiotherapy or due to the presence of plasmacytomas requiring some emergency.
• Participant who have received prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs.
• Participant has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to: belantamab mafodotin, lenalidomide, boronic acid (bortezomib), dexamethasone or any of the components of the study treatment.
• Participant who have had major surgery ≤ 4 weeks prior to initiating protocol therapy.
• Participant who have current corneal epithelial disease except mild punctate keratopathy
• Participant has peripheral neuropathy or neuropathic pain grade ≥2, as defined by the National Cancer Institute Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0 (APPENDIX 4).
• Participant is unable or unwilling to undergone antithrombotic prophylactic treatment
• Participant evidence of cardiovascular risk including any of the following:
• Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Type II) or 3rd degree atrioventricular (AV) block.

Sponsors & Collaborators

• PETHEMA Foundation: lead
• GlaxoSmithKline: collaborator

Study Sites (12)

Hospital Son Llatzer

Palma de Mallorca, Balearic Islands, 07198, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Universitario de Salamanca

Salamanca, Castille and León, 37007, Spain

Location

Complejo Universitario Hospitalario de Santiago

Santiago de Compostela, Galicia, 15706, Spain

Location

Hospital Gregorio Marañon

Madrid, Madrid, 28007, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Madrid, 28041, Spain

Location

Hospital de Cabueñes

Gijón, Principality of Asturias, 33394, Spain

Location

Hospital Universitario y Policlínico de la Fe

Valencia, Valencia, 46026, Spain

Location

Hospital Universitario de Gran Canaria Dr. Negrín

Las Palmas de Gran Canaria, Spain

Location

Hospital Infanta Leonor

Madrid, Spain

Location

Hospital General Universitario Morales Meseguer

Murcia, 30008, Spain

Location

Hospital Virgen de la Arrixaca

Murcia, Spain

Location

Related Publications (10)

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• Trudel S, Lendvai N, Popat R, Voorhees PM, Reeves B, Libby EN, Richardson PG, Hoos A, Gupta I, Bragulat V, He Z, Opalinska JB, Cohen AD. Antibody-drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: an update on safety and efficacy from dose expansion phase I study. Blood Cancer J. 2019 Mar 20;9(4):37. doi: 10.1038/s41408-019-0196-6.

  PMID: 30894515 BACKGROUND

• Trudel S, Lendvai N, Popat R, Voorhees PM, Reeves B, Libby EN, Richardson PG, Anderson LD Jr, Sutherland HJ, Yong K, Hoos A, Gorczyca MM, Lahiri S, He Z, Austin DJ, Opalinska JB, Cohen AD. Targeting B-cell maturation antigen with GSK2857916 antibody-drug conjugate in relapsed or refractory multiple myeloma (BMA117159): a dose escalation and expansion phase 1 trial. Lancet Oncol. 2018 Dec;19(12):1641-1653. doi: 10.1016/S1470-2045(18)30576-X. Epub 2018 Nov 12.

  PMID: 30442502 BACKGROUND

• Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, Abdallah AO, Callander N, Lendvai N, Sborov D, Suvannasankha A, Weisel K, Karlin L, Libby E, Arnulf B, Facon T, Hulin C, Kortum KM, Rodriguez-Otero P, Usmani SZ, Hari P, Baz R, Quach H, Moreau P, Voorhees PM, Gupta I, Hoos A, Zhi E, Baron J, Piontek T, Lewis E, Jewell RC, Dettman EJ, Popat R, Esposti SD, Opalinska J, Richardson P, Cohen AD. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. Lancet Oncol. 2020 Feb;21(2):207-221. doi: 10.1016/S1470-2045(19)30788-0. Epub 2019 Dec 16.

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• Cowan AJ, Allen C, Barac A, Basaleem H, Bensenor I, Curado MP, Foreman K, Gupta R, Harvey J, Hosgood HD, Jakovljevic M, Khader Y, Linn S, Lad D, Mantovani L, Nong VM, Mokdad A, Naghavi M, Postma M, Roshandel G, Shackelford K, Sisay M, Nguyen CT, Tran TT, Xuan BT, Ukwaja KN, Vollset SE, Weiderpass E, Libby EN, Fitzmaurice C. Global Burden of Multiple Myeloma: A Systematic Analysis for the Global Burden of Disease Study 2016. JAMA Oncol. 2018 Sep 1;4(9):1221-1227. doi: 10.1001/jamaoncol.2018.2128.

  PMID: 29800065 BACKGROUND

• McCarthy PL, Holstein SA, Petrucci MT, Richardson PG, Hulin C, Tosi P, Bringhen S, Musto P, Anderson KC, Caillot D, Gay F, Moreau P, Marit G, Jung SH, Yu Z, Winograd B, Knight RD, Palumbo A, Attal M. Lenalidomide Maintenance After Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: A Meta-Analysis. J Clin Oncol. 2017 Oct 10;35(29):3279-3289. doi: 10.1200/JCO.2017.72.6679. Epub 2017 Jul 25.

  PMID: 28742454 BACKGROUND

• Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, Arnulf B, Macro M, Belhadj K, Garderet L, Roussel M, Payen C, Mathiot C, Fermand JP, Meuleman N, Rollet S, Maglio ME, Zeytoonjian AA, Weller EA, Munshi N, Anderson KC, Richardson PG, Facon T, Avet-Loiseau H, Harousseau JL, Moreau P; IFM 2009 Study. Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma. N Engl J Med. 2017 Apr 6;376(14):1311-1320. doi: 10.1056/NEJMoa1611750.

  PMID: 28379796 BACKGROUND

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MeSH Terms

Conditions

Multiple Myeloma

Interventions

belantamab mafodotin; Bortezomib; Lenalidomide; Dexamethasone

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

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Maria Victoria Mateos Manteca, M.D.; Ph.D.

  Hospital Universitario de Salamanca (Salamanca)

  STUDY CHAIR

• Jesus San Miguel Izquierdo, M.D.; Ph.D.

  Clínica Universidad de Navarra (Pamplona)

  STUDY CHAIR

Study Design

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

Model Details: This is a multicenter, open label, non-randomized single arm clinical trial

Study Record Dates

• First Submitted: March 12, 2021
• First Posted: March 17, 2021
• Study Start: April 7, 2021
• Primary Completion: March 31, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: March 5, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

ES (12)