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High-Risk de Novo Multiple MyelomaPhase 2GEM-TECTALNCT05849610

Teclistamab-Daratumumab and Talquestamab-Daratumumab in Newly Diagnosed High-risk Multiple Myeloma

A Phase 2 study testing Daratumumab, Bortezomib and Lenalidomide in people with High-Risk de Novo Multiple Myeloma, run by PETHEMA Foundation at 10 sites in Spain.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

The goal of this Phase 2, open-label, multicenter, non-randomized pilot study is to evaluate the efficacy (in terms of MRD negative CR rate after Intensification therapy) and safety of Tec-Dara (Teclistamab+Daratumumab) and Tal-Dara (Talquetamab+Daratumumab) in de novo high-risk multiple myeloma (DNHRMM) patients. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
High-Risk de Novo Multiple Myeloma
What is being tested?
Daratumumab, Bortezomib and Lenalidomide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
10 sitesSpain
Study dates
21 Sep 2023to Jul 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements.
  • Patient has given voluntary written informed consent before performance of any study-related procedure nor part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
  • Patient is ≥ 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent.
  • Patient has documented diagnosis of multiple myeloma according to IMWG diagnostic criteria, with at least one of the following high-risk features:
  • High-risk FISH: del(17p), t(4;14), t(14;16) and 1q amplifications.
  • R-ISS 3
Show all 10Show fewer
  • Presence of extramedullary disease, defined as presence of paramedullary lesions or extramedullary plasmacytoma.
  • Note: In order to have a representative population with high-risk features, 50% of patients included will have ultra-high risk disease defined as: i) R-ISS 3; ii) Double hit (at least two high-risk cytogenetic abnormalities); iii) One high-risk cytogenetic abnormality + extramedullary disease.
  • Patients eligible for transplant with age ≤ 70 years old (young and transplant-eligible) or patients not eligible for transplant with ECOG-PS modified frailty score of 0-1 (elderly-fit).
  • Patient has an ECOG performance status of 0, 1or 2.

Who cannot join

  • Prior or current systemic therapy or SCT for any plasma cell dyscrasia, with the exception of 1 cycle of antimyeloma treatment or the emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before treatment while waiting for results of genetic analysis. A cycle of therapy may include treatment with proteasome inhibitors, immunomodulatory drugs, alkylators and corticosteroids, and/or anti-CD38 monoclonal antibodies (i.e, bortezomib-thalidomide-dexamethasone, D-VTD, bortezomib-lenalidomide-dexamethasone, or bortezomib-cyclophosphamide-dexamethasone, are valid options).
  • Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the NCI-CTCAE Version 5.
  • Patient has a diagnosis of primary light chain amyloidosis, monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), plasma cell leukemia or active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) at the time of screening.
  • Myelodysplastic syndrome or active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than relapsed/refractory multiple myeloma. The only allowed exceptions are malignancies treated within the last 24 months that are considered completely cured:
  • Non-muscle invasive bladder cancer (solitary Ta-papillary urothelial neoplasm of low malignancy or low grade, < 3 cm, no carcinoma in situ).
  • Skin cancer (non-melanoma skin cancers treated with curative therapy or localized melanoma treated with curative surgical resection alone).
Show all 11Show fewer
  • Noninvasive cervical cancer.
  • Localized prostate cancer (M0, N0) with a Gleason score of ≤ 7a, treated locally only (radical prostatectomy/radiation therapy/focal treatment).
  • Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, localized breast cancer and receiving antihormonal agents.
  • Other malignancy that is considered cured with minimal risk of recurrence.
  • Patient has CNS or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain MRI and lumbar cytology are required.

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

Spain10 sites

  • Hospital Germans Trials i Pujol

    Badalona

  • Hospital Clinic i Provincial de Barcelona

    Barcelona

  • Hospital Doce de Octubre

    Madrid, 28041

  • Hospital Virgen de la Arrixaca

    Murcia

  • Clinica Universidad de Navarra

    Pamplona

  • Hospital Universitario de Salamanca

    Salamanca

  • H. Universitario Marqués de Valdecilla

    Santander

  • Complejo Hospitalario Santiago (CHUS)

    Santiago de Compostela

  • Hospital Vírgen del Rocío

    Seville

  • Hospital Universitari i Politecnic la Fe

    Valencia

Other trials in Spain

About this study

Official title: An Open Label, Multicenter, Phase 2, Pilot Study, Evaluating Early Treatment With Bispecific T-cell Redirectors (Teclistamab and Talquetamab) in the Frontline Therapy of Newly Diagnosed High-risk Multiple Myeloma

The goal of this Phase 2, open-label, multicenter, non-randomized pilot study is to evaluate the efficacy (in terms of MRD negative CR rate after Intensification therapy) and safety of Tec-Dara (Teclistamab+Daratumumab) and Tal-Dara (Talquetamab+Daratumumab) in de novo high-risk multiple myeloma (DNHRMM) patients.

Read the detailed description

A total of 30 transplant eligible or elderly fit patients with high risk multiple myeloma will be enrolled

  1. Patients will receive a 4-cycle Dara+VRD (daratumumab, bortezomib, lenalidomide, dexamethasone) INDUCTION therapy. Cycles will be of 28 days (4-week cycles) in duration for daratumumab and for VRD.

After the 4-cycle Induction, all patients will receive the 1st INTENSIFICATION treatment which consists of 6 cycles of Tec-Dara. Cycles will be of 28 days (4-week cycles) in duration for daratumumab and for teclistamab.

1st Intsensification, patients will receive a 6-cycle Dara+Teclistamab.

  1. At the end of 1st Intensification timepoint treatments depends on MRD status:

2.1) MRD negative patients in CR at the end of Intensification will receive MAINTENANCE therapy with Tec-Dara continuously for 2 years. Cycles will be of 28-days in duration for Tec-Dara. Teclistamab (SC) and daratumumab (SC).

2.2) MRD positive patients or patients who didn't achieve CR despite MRD negativity, will have EARLY RESCUE INTERVENTION (ERI) with Tal-Dara for 6 cycles. MRD and response will be evaluated again after 6 cycles treatment with Tal-Dara. MRD negative patients in CR will receive continuous treatment with Tal-Dara for 2 years.

2.2.1 Early Rescue Intervention with Tal-Dara: Patients who are MRD+ after intensification or who convert from MRD negative into positive or experience a relapse from CR (without fulfilling criteria for disease progression) at any time during Tec-Dara treatment will have ERI with Tal-Dara. Cycles will be of 28 days in duration.

2.2.2. MRD negative patients in CR will receive continuous treatment with Tal-Dara for 2 years. Cycles will be of 28-days of duration for Tal-Dara.

  1. SALVAGE therapy: If the patient remains MRD+ or doesn't achieve CR despite MRD negativity after 6 cycles of ERI with Tal-Dara or has disease progression at any time, further treatment will be offered as per the investigation decision outside of the study.
Being tested
Daratumumab, Bortezomib, Lenalidomide, Teclistamab, Talquetamab
Keywords
High-Risk de novo Multiple Myeloma, Teclistamab, Talquetamab, Daratumumab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DaratumumabDrug

    Daratumumab will be administered by SC injection.

  • BortezomibDrug

    Bortezomib dose will be calculated using the patient's actual body surface area (BSA) at baseline and will be administered by subcutaneous (SC) injection.

  • LenalidomideDrug

    Lenalidomide will be administered by oral route.

  • TeclistamabDrug

    Also called JNJ-64007957

    Teclistamab will be administered by SC injection.

  • TalquetamabDrug

    Also called JNJ-64407564

    Talquetamab will be administered by subcutaneous (SC) injection.

Study groups in NCT05849610
Study groupRoleWhat they receive
Induction VRD-Dara + Intensification Tec-Dara + Maintenance Tec-Dara + ERI Tal-DaraExperimentalInduction (4 cycles) D-VRD. After Induction, all patients recieve 1st INTENSIFICATION treatment (6 cycles of Tec-Dara). Cycles will be of 28 days (4-week cycles) in duration for daratumumab and for Teclistamab. At the end of 1st Intensification timepoint treatments depends on MRD status: 1. MRD negative patients in CR at the end of Intensification will receive MAINTENANCE therapy with Tec-Dara continuously for 2 years. Crossover: patients who convert MRD positive or relapse from CR any time during Teclistamab maintenance will receive the same treatment as MRD positive individuals (early rescue intervention, ERI). 2. MRD positive patients or patients who didn't achieve CR despite MRD negativity, will have ERI (Tal-Dara 6 cycles). MRD and response will be evaluated again after 6 cycles treatment with Tal-Dara. MRD negative patients in CR will receive continuous treatment with Tal-Dara for 2 years.
Receives: Drug: Daratumumab; Drug: Bortezomib; Drug: Lenalidomide; Drug: Teclistamab; Drug: Talquetamab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Evaluate efficacy in terms of Measurable Residual Disease (MRD) negative Complete Remission rate by Next Generation Flow Cytometry after Teclistamab plus Daratumumab intensification.

    MRD measured by Next Generation Flow Cytometry (NGF, with a sensitivity level of 10-6) after 6 cycles of Tec-Dara therapy.

    Measured: 22 months approximately

  2. Evaluate efficacy in terms of Measurable Residual Disease (MRD) negative Complete Remission rate by Fluorodeoxyglucose Positron Emission Tomography-Computerized Tomography (FDG PET-CT) scan using the Deauville score, after Tec-Dara intensification.

    MRD measured by Fluorodeoxyglucose Positron Emission Tomography-Computerized Tomography (FDG PET-CT) scan.

    Measured: 22 months approximately

Secondary outcomes (13)

  1. To evaluate MRD negative CR rate after Daratumumab plus bortezomib, lenalidomide and dexamethasone (D-VRD) induction.

    MRD measured by Next Generation Flow Cytometry.

    Measured: 16 months approximately

  2. To evaluate MRD negativity after Teclistamab plus Daratumumab (Tec-Dara) intensification using alternative methods

    MRD negative rates measured by Next Generation Sequencing (NGS), and Quantitative Immunoprecipitation Free Light Chain Mass Spectrometry (QIP-FLC-MS) after 6 cycles of Tec-Dara therapy.

    Measured: 22 months approximately

  3. To evaluate MRD conversion after early rescue intervention with Talqutamab plus Daratumumab (Tal-Dara)

    Percentage of patients converting from positive MRD to negative MRD evaluated by NGF, NGS, QIP-MS-FLC and FDG-PET-CT scan.

    Measured: 4 years approximately

  4. To evaluate MRD conversion after Tec-Dara intensification

    Percentage of patients converting from positive MRD after D-VRD induction to negative MRD evaluated by NGF, NGS, QIP-MS-FLC and FDGPET-CT scan after Tec-Dara intensification.

    Measured: 22 months approximately

  5. To evaluate sustained MRD negativity during maintenance treatment in both Tec-Dara and Tal-Dara treatment arms

    Proportion of patients with persistent MRD negative disease at month 6, 12, 18 and 24 of maintenance treatment in both Tec-Dara and TalDara treatment, by NGF, NGS, QIP-MS-FLC and FDG-PET-CT scan and annually thereafter.

    Measured: 76 months approximately

  6. To assess reappearance of MRD positivity or relapse from CR in patients during the Tec-Dara treatment.

    Proportion of patients relapsing from MRD negative CR to MRD positive or who relapse from CR (not fulfilling criteria for disease progression) during any phase of Tec-Dara treatment (intensification or maintenance).

    Measured: 46 months

  7. To assess Time to PFS

    PFS is defined as the time from the date of first dose of study drug to the date of first documented disease progression, as defined in the International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occurs first. For subjects who have not progressed and are alive, data will be censored at the last disease evaluation before the start of any subsequent anti-myeloma therapy. PFS is measured in months.

    Measured: 76 months approximately

  8. To assess Time to EFS

    EFS is defined as the time from the date of first dose of study drug to the date of first documentation of an event. Definition of event for EFS calculation is: relapse from CR, conversion from Measurable Residual Disease (MRD) negativity (absence of phenotypically aberrant clonal plasma cells by next generation flow with a sensitivity level of 10-6 using the EuroFlow standard operation procedure and complete metabolic response by PET-CT (Deauville score ≤ 3)) to MRD positivity (presence of phenotypically aberrant clonal plasma cells by next generation flow with a sensitivity level of 10-6 using the EuroFlow standard operation procedure and complete metabolic response by PET-CT (Deauville score ≤ 3)), disease progression or death due to any cause, whichever occurs first. For subjects who have not experience any of these events, data will be censored at the last visit. EFS is measured in months.

    Measured: 76 months approximately

  9. To assess Time to TNT

    TNT is defined as the time between date of first dose of study drug and the first dose of the next treatment received. TNT is measured in months.

    Measured: 76 months approximately

  10. To assess Time to DoR

    DoR is the date of initial documentation of a response (Partial Response or better) to the date of first documented evidence of progressive disease, as defined in the International Myeloma Working Group (IMWG) criteria. Relapse from complete response is not considered as disease progression. For subjects who have not progressed, data will be censored at the last disease evaluation before the start of any subsequent anti-myeloma therapy. DoR is measured in months

    Measured: 76 months approximately

  11. To assess Time to OS

    OS is defined as the time from the date of first dose of study drug to the date of the subject's death. If the subject is alive or the vital status is unknown, then the subject's data will be censored at the date the subject was last known to be alive. OS is measured in months.

    Measured: 76 months approximately

  12. To assess the safety of the treatment described in the protocol

    Incidence of treatment-emergent adverse events

    Measured: 76 months approximately

  13. Immune profiling and genetic characterization

    Analysis of immune subpopulation and genetic markers

    Measured: 76 months approximately

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 May 2023
  2. Study start21 Sep 2023
  3. Primary completion3 Mar 2026
  4. Study completionJul 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05849610
Sponsor's protocol ID
GEM-TECTAL
Acronym
GEM-TECTAL
Status last verified
May 2026
First submitted
24 Feb 2023
Last updated
11 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Abecma® (idecabtagene vicleucel) [United States Prescribing Information]. Summit, NJ. Celgene Corporation; 2021.

  • Adams HC 3rd, Stevenaert F, Krejcik J, Van der Borght K, Smets T, Bald J, Abraham Y, Ceulemans H, Chiu C, Vanhoof G, Usmani SZ, Plesner T, Lonial S, Nijhof I, Lokhorst HM, Mutis T, van de Donk NWCJ, Sasser AK, Casneuf T. High-Parameter Mass Cytometry Evaluation of Relapsed/Refractory Multiple Myeloma Patients Treated with Daratumumab Demonstrates Immune Modulation as a Novel Mechanism of Action. Cytometry A. 2019 Mar;95(3):279-289. doi: 10.1002/cyto.a.23693. Epub 2018 Dec 11.

    PubMed 30536810

  • Ariza-Heredia EJ, Chemaly RF. Practical review of immunizations in adult patients with cancer. Hum Vaccin Immunother. 2015;11(11):2606-14. doi: 10.1080/21645515.2015.1062189. Epub 2015 Jun 25.

    PubMed 26110220

  • Atamaniuk J, Gleiss A, Porpaczy E, Kainz B, Grunt TW, Raderer M, Hilgarth B, Drach J, Ludwig H, Gisslinger H, Jaeger U, Gaiger A. Overexpression of G protein-coupled receptor 5D in the bone marrow is associated with poor prognosis in patients with multiple myeloma. Eur J Clin Invest. 2012 Sep;42(9):953-60. doi: 10.1111/j.1365-2362.2012.02679.x. Epub 2012 May 16.

    PubMed 22591013

  • Bai S, Jorga K, Xin Y, Jin D, Zheng Y, Damico-Beyer LA, Gupta M, Tang M, Allison DE, Lu D, Zhang Y, Joshi A, Dresser MJ. A guide to rational dosing of monoclonal antibodies. Clin Pharmacokinet. 2012 Feb 1;51(2):119-35. doi: 10.2165/11596370-000000000-00000.

    PubMed 22257150

  • Bergsagel PL, Mateos MV, Gutierrez NC, Rajkumar SV, San Miguel JF. Improving overall survival and overcoming adverse prognosis in the treatment of cytogenetically high-risk multiple myeloma. Blood. 2013 Feb 7;121(6):884-92. doi: 10.1182/blood-2012-05-432203. Epub 2012 Nov 19.

    PubMed 23165477

  • Brauner-Osborne H, Jensen AA, Sheppard PO, Brodin B, Krogsgaard-Larsen P, O'Hara P. Cloning and characterization of a human orphan family C G-protein coupled receptor GPRC5D. Biochim Biophys Acta. 2001 Apr 16;1518(3):237-48. doi: 10.1016/s0167-4781(01)00197-x.

    PubMed 11311935

  • Burtis CA, Ashwood ER. Tietz textbook of clinical chemistry. 3rd ed. Philadelphia: WB Sauders; 1998.

  • Carpenter RO, Evbuomwan MO, Pittaluga S, Rose JJ, Raffeld M, Yang S, Gress RE, Hakim FT, Kochenderfer JN. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res. 2013 Apr 15;19(8):2048-60. doi: 10.1158/1078-0432.CCR-12-2422. Epub 2013 Jan 23.

    PubMed 23344265

  • Darce JR, Arendt BK, Chang SK, Jelinek DF. Divergent effects of BAFF on human memory B cell differentiation into Ig-secreting cells. J Immunol. 2007 May 1;178(9):5612-22. doi: 10.4049/jimmunol.178.9.5612.

    PubMed 17442944

  • Delforge M, Ludwig H. How I manage the toxicities of myeloma drugs. Blood. 2017 Apr 27;129(17):2359-2367. doi: 10.1182/blood-2017-01-725705. Epub 2017 Mar 8.

    PubMed 28275090

  • Dimopoulos MA, Moreau P, Terpos E, Mateos MV, Zweegman S, Cook G, Delforge M, Hajek R, Schjesvold F, Cavo M, Goldschmidt H, Facon T, Einsele H, Boccadoro M, San-Miguel J, Sonneveld P, Mey U. Multiple Myeloma: EHA-ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up. Hemasphere. 2021 Feb 3;5(2):e528. doi: 10.1097/HS9.0000000000000528. eCollection 2021 Feb. No abstract available.

    PubMed 33554050

  • Drayson MT, Bowcock S, Planche T, Iqbal G, Pratt G, Yong K, Wood J, Raynes K, Higgins H, Dawkins B, Meads D, Hulme CT, Monahan I, Karunanithi K, Dignum H, Belsham E, Neilson J, Harrison B, Lokare A, Campbell G, Hamblin M, Hawkey P, Whittaker AC, Low E, Dunn JA; TEAMM Trial Management Group and Trial Investigators. Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial. Lancet Oncol. 2019 Dec;20(12):1760-1772. doi: 10.1016/S1470-2045(19)30506-6. Epub 2019 Oct 23.

    PubMed 31668592

  • ECOG-ACRIN Cancer Research Group. ECOG Performance Status Scale. Available at: http://ecogacrin.org/resources/ecog-performance-status. Accessed 28 September 2022.

  • Facon T, Dimopoulos MA, Meuleman N, Belch A, Mohty M, Chen WM, Kim K, Zamagni E, Rodriguez-Otero P, Renwick W, Rose C, Tempescul A, Boyle E, Manier S, Attal M, Moreau P, Macro M, Leleu X, Lorraine Chretien M, Ludwig H, Guo S, Sturniolo M, Tinel A, Silvia Monzini M, Costa B, Houck V, Hulin C, Yves Mary J. A simplified frailty scale predicts outcomes in transplant-ineligible patients with newly diagnosed multiple myeloma treated in the FIRST (MM-020) trial. Leukemia. 2020 Jan;34(1):224-233. doi: 10.1038/s41375-019-0539-0. Epub 2019 Aug 19.

    PubMed 31427722

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Daratumumab, Bortezomib and Lenalidomide in people with High-Risk de Novo Multiple Myeloma, run by PETHEMA Foundation at 10 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 11 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Evaluate efficacy in terms of Measurable Residual Disease (MRD) negative Complete Remission rate by Next Generation Flow Cytometry after Teclistamab plus Daratumumab intensification. (time frame: 22 months approximately). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05849610, which also lists 56 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2026.

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