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

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05218603
• Other study ID #: GEM-OPTIMAL
• Status: Recruiting
• Start date: November 30, 2021
• Est. completion date: November 6, 2025

Study information

• Verified date: September 2022
• Source: PETHEMA Foundation
• Contact: Carmen López-Carrero
• Phone: 0034 699 835 437
• Email: carmen[@]fundacionpethema.es
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: November 6, 2025
• Est. primary completion date: November 6, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Bortezomib
Maintenance: Administration as per routine clinical practice.
• Daratumumab
Maintenance: Administration as per routine clinical practice.

Locations

Country	Name	City	State
Spain	Hospital Universitario Del Sureste	Arganda Del Rey
Spain	Complejo Asistencial de Avila	Ávila
Spain	Hospital Quirón Sagrado Corazón	Barcelona
Spain	Hsopital Clinic de Barcelona	Barcelona
Spain	Hospital Universitario Virgen de Las Nieves	Granada
Spain	Complejo Hospitalario de Jaén	Jaén
Spain	Hospital Universitario de Canarias (H.U.C)	La Laguna
Spain	Complejo Hospitalario Universitario de Gran Canaria Dr. Negrín	Las Palmas De Gran Canaria
Spain	Hospital de León	León
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Ramón Y Cajal	Madrid
Spain	Hospital Ruber Juan Bravo 39	Madrid
Spain	Hospital Universitario de La Princesa	Madrid
Spain	Hospital Universitario Fundación Jiménez Díaz	Madrid
Spain	Hospital Universitario Infanta Leonor	Madrid
Spain	Hospital General Universitario J.M. Morales Meseguer	Murcia
Spain	Complexo Hospitalario Universitario de Ourense	Ourense
Spain	Hospital Universitario Central de Asturias	Oviedo
Spain	Clinica Universidad de Navarra	Pamplona
Spain	Hospital Virgen Del Puerto	Plasencia
Spain	Hospital El Bierzo	Ponferrada
Spain	Hospital Montecelo	Pontevedra
Spain	Hospital Quirónsalud Madrid	Pozuelo De Alarcón
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Infanta Sofía	San Sebastián De Los Reyes
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Spain	Hospital Clinico Universitario de Santiago	Santiago De Compostela
Spain	Hospital General Nuestra Señora Del Prado	Talavera De La Reina
Spain	Hospital Universitari Mútua de Terrassa	Terrassa
Spain	Hospital General de Tomelloso	Tomelloso
Spain	Hospital Clinico Universitario de Valladolid	Valladolid

Sponsors (3)

Lead Sponsor	Collaborator
PETHEMA Foundation	Adknoma Health Research, Janssen, LP

Country where clinical trial is conducted

Spain, 

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* Note: There are 36 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Stringent Complete Response (sCR) rate		Throughout the study period. Approximately 4 years
Secondary	Complete Response (CR) rate		Throughout the study period. Approximately 4 years
Secondary	Proportion of subjects who achieve Very Good Partial Response (VGPR) or better		Throughout the study period. Approximately 4 years
Secondary	Overall Response Rate (ORR)		Throughout the study period. Approximately 4 years
Secondary	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
Secondary	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
Secondary	Incidence of adverse events (AEs)	Number of patients experiencing AEs, classified according to severity.	Throughout the study period. Approximately 4 years