Evaluation of Maintenance With Bortezomib Plus Daratumumab (V-Dara) After Induction With Bortezomib, Melphalan, Prednisone Plus Daratumumab (VMP-Dara) in Newly Diagnosed Multiple Myeloma (MM) Patients Non-eligible for autoSCT

A Prospective, Observational Study, to Evaluate the Maintenance With Bortezomib Plus Daratumumab (V-Dara) After Induction With Bortezomib, Melphalan, Prednisone Plus Daratumumab (VMP-Dara) in Newly Diagnosed Multiple Myeloma (MM) Patients Non-eligible for Autologous Stem Cell Transplantation (ASCT): Alcyone-optimized Real World Evidence (RWE) Data

This is a prospective, observational, single group and multicenter study to describe the effectiveness and safety of maintenance with V-Dara after induction with the VMP-Dara regimen in newly diagnosed MM patients who are not eligible for ASCT.

Patients will be enrolled in the study during a regularly scheduled office visit in clinical practice (screening and enrollment visit) and followed during 3-4 years in what will be called the Observational Phase. During this phase, the patient will be followed by his/her doctor as per routine clinical practice, according to his/her disease. The patient will not suffer any changes in his/her treatment or follow-up due to his/her participation in the study. The patient will receive standard clinical practice and he/she will not do any other study-specific visit.

During this 3-4-year observational phase, the patient might discontinue V or V-Dara,depending on toxicity, efficacy or due to other medical reasons, according to his/her physician decision.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma; Non-eligible for Autologous Stem Cell Transplantation (ASCT)
• Intervention / Treatment: Drug: Bortezomib; Drug: Daratumumab

Detailed Description

This is a prospective, observational, single group and multicenter study to describe the effectiveness and safety of maintenance with V-Dara after induction with the VMP-Dara regimen in newly diagnosed MM patients who are not eligible for ASCT.

Patients will be recruited only if patients have received induction therapy with VMP-Dara followed by V-Dara as maintenance therapy for at least one cycle prior to the start of the study (treatment has to be previously decided as part of clinical practice). This way, patients must have already been treated with 9 cycles of VMP-Dara (approximately 12 months) and at least 1 cycle of V-Dara maintenance (1 month), before entering the study. This implies that the decision to prescribe this maintenance schedule is clearly unrelated to the decision of enrolling the patient into the study.

Patients will be enrolled in the study during a regularly scheduled office visit in clinical practice (screening and enrollment visit) and followed during 3-4 years in what will be called the Observational Phase. During this phase, the patient will be followed by his/her doctor as per routine clinical practice, according to his/her disease. The patient will not suffer any changes in his/her treatment or follow-up due to his/her participation in the study. The patient will receive standard clinical practice and he/she will not do any other study-specific visit.

Observational Phase:

Patients will be followed for 3-4 years since the inclusion in the study. Once the patient is enrolled in the study, retrospective data collection at the start and end of VMP-Dara induction will be collected. Subjects who discontinue maintenance therapy before disease progression (V or V-Dara), will continue to have response rate evaluations, PFS and toxicity recorded as per routine clinical practice, until the end of the study or progression, whatever comes first.

During this observational follow-up, both the duration of the initially prescribed V-Dara maintenance (and the time when bortezomib is stopped before daratumumab if this ever happens), the existence of potential adverse reactions and the fate of the disease in terms of progression and survival, even though the maintenance only daratumumab could have been stopped, will be documented for a total of up to 3-4 years. Maintenance with V-Dara, or just daratumumab once bortezomib is suspended, can be finalized due to progression, unacceptable toxicity or voluntary withdrawal.

This observational study has the following objectives:

Primary Objective:

- To describe the effectiveness of V-Dara maintenance after VMPDara induction in patients with MM non-eligible for autologous stem cell transplantation in the Spanish clinical setting (clinical practice).

Secondary Objectives:

• Compare the effectiveness of VMP-Dara induction followed by V-Dara maintenance with the results of the Daratumumab arm of the Alcyone trial (VMP-Dara followed by Dara maintenance).
• To describe the safety of the V-Dara maintenance therapy used in clinical practice after VMP-Dara.
• To evaluate the clinical effectiveness in different risk subgroups.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Carmen López-Carrero; Phone Number: 0034 699 835 437; Email: carmen@fundacionpethema.es
• Study Contact Backup: Name: Roberto Maldonado; Phone Number: 0034 683 15 66 87; Email: roberto.maldonado@fundacionpethema.es

Study Locations

• Spain
  • Arganda Del Rey, Spain
    • Recruiting
    • Hospital Universitario Del Sureste
    • Contact: Teresa Cobo Rodríguez
    • Principal Investigator: Teresa Cobo Rodríguez
  • Barcelona, Spain
    • Recruiting
    • Hospital Quiron Sagrado Corazon
    • Contact: Miguel Sánchez Rey
    • Principal Investigator: Miguel Sánchez Rey
  • Barcelona, Spain
    • Recruiting
    • Hsopital Clinic de Barcelona
    • Contact: Laura Rosiñol
    • Principal Investigator: Laura Rosiñol
  • Granada, Spain
    • Not yet recruiting
    • Hospital Universitario Virgen de las Nieves
    • Contact: Esther Clavero Sánchez
    • Principal Investigator: Esther Clavero Sánchez
  • Jaén, Spain
    • Recruiting
    • Complejo Hospitalario de Jaén
    • Contact: Magdalena Anguita
    • Principal Investigator: Magdalena Anguita
  • La Laguna, Spain
    • Recruiting
    • Hospital Universitario de Canarias (H.U.C)
    • Contact: Miguel Teodoro Hernández García
    • Principal Investigator: Miguel Teodoro Hernández García
  • Las Palmas De Gran Canaria, Spain
    • Recruiting
    • Complejo Hospitalario Universitario de Gran Canaria Dr. Negrín
    • Contact: Alexia Suárez Cabrera
    • Principal Investigator: Alexia Suarez Cabrera
  • León, Spain
    • Recruiting
    • Hospital de Leon
    • Principal Investigator: Fernando Escalante
    • Contact: Fernando Escalante
  • Madrid, Spain
    • Recruiting
    • Hospital General Universitario Gregorio Maranon
    • Contact: Cristina Encinas
    • Principal Investigator: Cristina Encinas
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario Infanta Leonor
    • Principal Investigator: Jose Angel Hernandez Rivas
    • Contact: Jose Angel Hernandez Rivas
  • Madrid, Spain
    • Recruiting
    • Hospital Ramon y Cajal
    • Contact: Maria Jesús Blanchard
    • Principal Investigator: Maria Jesús Blanchard
  • Madrid, Spain
    • Not yet recruiting
    • Hospital Clinico San Carlos
    • Contact: Belén Íñigo
    • Principal Investigator: Belén Íñigo
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario Fundacion Jimenez Diaz
    • Principal Investigator: Elena Prieto Pareja
    • Contact: Elena Prieto Pareja
  • Madrid, Spain
    • Recruiting
    • Hospital Ruber Juan Bravo 39
    • Contact: Arancha Alonso
    • Principal Investigator: Arancha Alonso
  • Madrid, Spain
    • Not yet recruiting
    • Hospital Universitario de la Princesa
    • Contact: Adrián Alegre
    • Principal Investigator: Adrián Alegre
  • Murcia, Spain
    • Recruiting
    • Hospital General Universitario J.M. Morales Meseguer
    • Principal Investigator: Felipe De Arriba de la Fuente
    • Contact: Felipe De Arriba De la Fuente
  • Ourense, Spain
    • Recruiting
    • Complexo Hospitalario Universitario de Ourense
    • Contact: José Ángel Méndez
    • Principal Investigator: José Ángel Méndez
  • Oviedo, Spain
    • Recruiting
    • Hospital Universitario Central de Asturias
    • Contact: Ángel Ramirez Payer
  • Pamplona, Spain
    • Recruiting
    • Clinica Universidad de Navarra
    • Contact: Paula Rodríguez
    • Principal Investigator: Paula Rodríguez
  • Plasencia, Spain
    • Recruiting
    • Hospital Virgen del Puerto
    • Contact: Rosa María López López
    • Principal Investigator: Rosa María López López
  • Ponferrada, Spain
    • Recruiting
    • Hospital El Bierzo
    • Contact: Carmen Aguilera
    • Principal Investigator: Carmen Aguilera
  • Pontevedra, Spain
    • Recruiting
    • Hospital Montecelo
    • Contact: Ana Dios Loureiro
    • Principal Investigator: Ana Dios Loureiro
  • Pozuelo De Alarcón, Spain
    • Recruiting
    • Hospital Quirónsalud Madrid
    • Principal Investigator: Carmen Martinez Chamorro
    • Contact: Carmen Martínez Chamorro
  • Salamanca, Spain
    • Recruiting
    • Hospital Universitario de Salamanca
    • Contact: Maria Victoria Mateos Manteca
  • San Sebastián De Los Reyes, Spain
    • Recruiting
    • Hospital Universitario Infanta Sofía
    • Principal Investigator: Eugenio Giménez Mesa
    • Contact: Eugenio Giménez Mesa
  • Santander, Spain
    • Recruiting
    • Hospital Universitario Marques de Valdecilla
    • Contact: enrique ocio
    • Principal Investigator: Enrique Ocio
  • Santiago De Compostela, Spain
    • Recruiting
    • Hospital Clinico Universitario de Santiago
    • Contact: Marta Sonia González Pérez
    • Principal Investigator: Marta Sonia González Pérez
  • Talavera De La Reina, Spain
    • Not yet recruiting
    • Hospital General Nuestra Señora del Prado
    • Contact: Ana Lerma
    • Principal Investigator: Ana Lerma
  • Terrassa, Spain
    • Recruiting
    • Hospital Universitari Mutua de Terrassa
    • Contact: Josep Martí
    • Principal Investigator: Josep Martí
  • Tomelloso, Spain
    • Not yet recruiting
    • Hospital General de Tomelloso
    • Contact: Mónica López Rincón
    • Principal Investigator: Mónica López Rincón
  • Valladolid, Spain
    • Recruiting
    • Hospital Clínico Universitario de Valladolid
    • Contact: Alfonso García de Coca
    • Principal Investigator: Alfonso García de Coca
  • Ávila, Spain
    • Recruiting
    • Complejo Asistencial de Ávila
    • Contact: Abelardo Bárez García
    • Principal Investigator: Abelardo Bárez García

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

A target of approximately 100 subjects from the centers opened in the study will be recruited only if patients have received induction therapy with VMP-Dara followed by V-Dara as maintenance therapy for at least one cycle prior to the start of the study (treatment has to be previously decided as part of clinical practice). This way, patients must have already been treated with 9 cycles of VMP-Dara (approximately 12 months) and at least 1 cycle of V-Dara maintenance (1 month), before entering the study. This implies that the decision to prescribe this maintenance schedule is clearly unrelated to the decision of enrolling the patient into the study.

Description

Inclusion Criteria:

1. Patients with a newly diagnosed MM non eligible for ASCT that have received induction therapy with D-VMP (9 cycles) and followed by V-Dara as maintenance* in clinical practice. The decision to prescribe maintenance treatment with V-Dara must be in accordance with clinical practice, must not be influenced by the planned inclusion of a patient in the study, and should be documented before enrollment.
2. Patients ≥18 years of age.
3. Each subject (or their legally acceptable representative) must sign the ICF indicating that he or she understands the purpose of the observational nature the study and are willing to share his/her clinical data for the study.

Exclusion Criteria:

1. Patients with a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, smoldering MM, plasma cell leukemia, POEMS syndrome, Waldenström's disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.
2. Subjects with prior or current systemic therapy or ASCT for MM (before VMP-Dara induction), except for an emergency use of a short course of corticosteroids before treatment.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Maintenance with V-Dara after receiving VMP-Dara as induction regimen; Maintenance with bortezomib plus daratumumab (V-Dara) after induction with bortezomib, melphalan, prednisone plus daratumumab (VMP-Dara)	Drug: Bortezomib; Maintenance: Administration as per routine clinical practice.; Drug: Daratumumab; Maintenance: Administration as per routine clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	Time from the start of induction with VMPDara until disease progression or death, whichever comes first	Throughout the study period. Approximately 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Description of MRD status and depth	Description of MRD status and depth, that will be conducted on bone marrow samples and outside of the bone marrow through imaging techniques if available per routine clinical practice, according to the investigator's criteria.	Throughout the study period. Approximately 4 years
Stringent Complete Response (sCR) rate		Throughout the study period. Approximately 4 years
Complete Response (CR) rate		Throughout the study period. Approximately 4 years
Proportion of subjects who achieve Very Good Partial Response (VGPR) or better		Throughout the study period. Approximately 4 years
Overall Response Rate (ORR)		Throughout the study period. Approximately 4 years
Duration of response	Duration of response calculated from the date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease.	Throughout the study period. Approximately 4 years
Time to Progression (TTP)	Time to Progression (TTP), defined as the time from the date of start of VMP-Dara to the date of first documented evidence of PD.	Throughout the study period. Approximately 4 years
Incidence of adverse events (AEs)	Number of patients experiencing AEs, classified according to severity.	Throughout the study period. Approximately 4 years

Collaborators and Investigators

• Sponsor: PETHEMA Foundation
• Collaborators: Janssen, LP; Adknoma Health Research
• Investigators: Principal Investigator: María Victoria Mateos Manteca, Hospital Universitario de Salamanca (Salamanca); Principal Investigator: Jesús San Miguel Izquierdo, Clínica Universidad de Navarra (Pamplona)

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2021
• Primary Completion (Anticipated): November 6, 2025
• Study Completion (Anticipated): November 6, 2025

Study Registration Dates

• First Submitted: January 17, 2022
• First Submitted That Met QC Criteria: January 28, 2022
• First Posted (Actual): February 1, 2022

Study Record Updates

• Last Update Posted (Actual): September 16, 2022
• Last Update Submitted That Met QC Criteria: September 15, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Observational study; Prospective
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Antineoplastic Agents; Daratumumab; Bortezomib
• Other Study ID Numbers: GEM-OPTIMAL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No