Efficacy of Response-adapted Treatment in Patients With Multiple Myeloma Candidates for Bone Marrow Transplantation

NCT05697913 | Active Not Recruiting DMC

• 1 other identifier: MRD-Image neg 01
• Study Type: interventional
• Target: 66
• Locations: 0 countries
• Sites: N/A

Brief Summary

To assess whether continued treatment to achieve negative Minimal Residual Disease and Imaging (MRDI(-)) improves therapeutic outcomes in patients with newly diagnosed Multiple Myeloma. The primary endpoints are progression-free survival (PFS) and overall survival (OS). The safety evaluation includes the evaluation of adverse events, which are classified according to the Common Criteria for Terminology for Adverse Events of the National Cancer Institute, version 5.0.

Conditions

Multiple Myeloma

Keywords

Minimal Residual Disease; Therapeutics; Multiple Myeloma

Outcome Measures

Primary Outcomes (5)

• Progression Free Survival

  Time elapsed from start of treatment until first documentation of disease progression or date of death from any cause, whichever came first.

  Time elapsed from start of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 120 months.

• Overall Survival

  Time from start of treatment to death from any cause

  Time elapsed from start of treatment to end of follow-up or patient death, whichever came first, assessed up to 120 months.

• Proportion of patients with serious adverse effects

  Number of patients with any adverse event grade 3 or higher, divided by the total number of patients in the corresponding group

  Time elapsed from start of treatment to end of follow-up or patient death, whichever came first, assessed up to 102 months.

• Average grade 3 or higher adverse events per patient

  Number of grade 3 or higher adverse events in the group divided by the number of patients in the group

  Time elapsed from start of treatment to end of follow-up or patient death, whichever came first, assessed up to 120 months.

• Annual incidence of grade 3 or higher adverse effects

  Number of grade 3 or higher adverse events in the group divided by the sum of the years of observation of the group members

  Time elapsed from start of treatment to end of follow-up or patient death, whichever came first, assessed up to 102 months.

Study Arms (2)

MRDI-driven treatment

EXPERIMENTAL

Patients continue treatment until complete remission with negative MRD and Image is achieved, changing the therapeutic line if this is not achieved with the prescribed treatment. In this group of patients, treatment is suspended only when this degree of profound response is reached, in any phase of treatment.

Other: Continued treatment adapted to the response

Conventional treatment

NO INTERVENTION

The patients of the conventional treatment group (control group) received six cycles of the induction traetment, bone marrow auto-transplantation, and consolidation treatment after transplantation if complete remission had not been achieved.

Interventions

Continued treatment adapted to the response OTHER

Instead of receiving a pre-specified number of treatment cycles, regardless of the result obtained, in the MRDI-driven treatment group patients continue receiving treatment until reaching a complete remission with negative MRD and Image, changing the therapeutic line if it is not obtained with the line current therapy. In this group of the patients the treatment was stopped only when this degree of deep response was achieved.

MRDI-driven treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Younger than 76 years
• Diagnosed with Multiple Myeloma from July 1, 2014 to May 31, 2019
• Received some of the standard authorized treatments for their therapeutic line. Patients treated in clinical trials with treatments not yet authorized, for fifth or successive therapeutic lines are admitted.
• Give informed consent
• Fit patient

You may not qualify if:

• Under 18 years old
• Contraindication for bone marrow auto-transplantation
• Therapeutic objective only palliative:
• Another non-treatable neoplasm
• Severe senile dementia
• Significant comorbidity limiting life expectancy to less than 6 months

Sponsors & Collaborators

• Hospital Galdakao-Usansolo: lead

Related Publications (5)

• Ludwig H, Zojer N. Fixed duration vs continuous therapy in multiple myeloma. Hematology Am Soc Hematol Educ Program. 2017 Dec 8;2017(1):212-222. doi: 10.1182/asheducation-2017.1.212.

  PMID: 29222258 BACKGROUND

• Jackson GH, Davies FE, Pawlyn C, Cairns DA, Striha A, Collett C, Waterhouse A, Jones JR, Kishore B, Garg M, Williams CD, Karunanithi K, Lindsay J, Wilson JN, Jenner MW, Cook G, Kaiser MF, Drayson MT, Owen RG, Russell NH, Gregory WM, Morgan GJ; UK NCRI Haematological Oncology Clinical Studies Group. Response-adapted intensification with cyclophosphamide, bortezomib, and dexamethasone versus no intensification in patients with newly diagnosed multiple myeloma (Myeloma XI): a multicentre, open-label, randomised, phase 3 trial. Lancet Haematol. 2019 Dec;6(12):e616-e629. doi: 10.1016/S2352-3026(19)30167-X. Epub 2019 Oct 14.

  PMID: 31624047 BACKGROUND

• Paiva B, Puig N, Cedena MT, Rosinol L, Cordon L, Vidriales MB, Burgos L, Flores-Montero J, Sanoja-Flores L, Lopez-Anglada L, Maldonado R, de la Cruz J, Gutierrez NC, Calasanz MJ, Martin-Ramos ML, Garcia-Sanz R, Martinez-Lopez J, Oriol A, Blanchard MJ, Rios R, Martin J, Martinez-Martinez R, Sureda A, Hernandez MT, de la Rubia J, Krsnik I, Moraleda JM, Palomera L, Bargay J, Van Dongen JJM, Orfao A, Mateos MV, Blade J, San-Miguel JF, Lahuerta JJ; GEM (Grupo Espanol de Mieloma)/PETHEMA (Programa Para el Estudio de la Terapeutica en Hemopatias Malignas) Cooperative Study Group. Measurable Residual Disease by Next-Generation Flow Cytometry in Multiple Myeloma. J Clin Oncol. 2020 Mar 10;38(8):784-792. doi: 10.1200/JCO.19.01231. Epub 2019 Nov 26.

  PMID: 31770060 BACKGROUND

• Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, Munshi N, Lonial S, Blade J, Mateos MV, Dimopoulos M, Kastritis E, Boccadoro M, Orlowski R, Goldschmidt H, Spencer A, Hou J, Chng WJ, Usmani SZ, Zamagni E, Shimizu K, Jagannath S, Johnsen HE, Terpos E, Reiman A, Kyle RA, Sonneveld P, Richardson PG, McCarthy P, Ludwig H, Chen W, Cavo M, Harousseau JL, Lentzsch S, Hillengass J, Palumbo A, Orfao A, Rajkumar SV, Miguel JS, Avet-Loiseau H. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016 Aug;17(8):e328-e346. doi: 10.1016/S1470-2045(16)30206-6.

  PMID: 27511158 BACKGROUND

• Zamagni E, Nanni C, Mancuso K, Tacchetti P, Pezzi A, Pantani L, Zannetti B, Rambaldi I, Brioli A, Rocchi S, Terragna C, Martello M, Marzocchi G, Borsi E, Rizzello I, Fanti S, Cavo M. PET/CT Improves the Definition of Complete Response and Allows to Detect Otherwise Unidentifiable Skeletal Progression in Multiple Myeloma. Clin Cancer Res. 2015 Oct 1;21(19):4384-90. doi: 10.1158/1078-0432.CCR-15-0396. Epub 2015 Jun 15.

  PMID: 26078390 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma; Neoplasm, Residual

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jose Enrique de la Puerta Rueda, MD

  Hospital Cruz Roja de Bilbao

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Prospective, no randomized. It is a cohort study to compare MRDI(-) driven treatment adapted to the response versus fixed-duration therapy.

Study Record Dates

• First Submitted: December 25, 2022
• First Posted: January 26, 2023
• Study Start: July 1, 2014
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2024
• Last Updated: March 6, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share