Multiple Myeloma RefractoryPhase 2GEM-MeziDELNCT07901868
Elranatamab With Mezigdomide and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma
A Phase 2 study testing Dexamethasone, Mezigdomide and Elranatamab in people with Multiple Myeloma Refractory and Multiple Myeloma in Relapse, run by PETHEMA Foundation at 20 sites in Spain.
Trial summary
The goal of this clinical trial is to learn if the drug combination Elranatamab plus Mezigdomide plus Dexametahsone works to cure patients with relapsed/refractory multiple myeloma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma Refractory, Multiple Myeloma in Relapse
- What is being tested?
- Dexamethasone, Mezigdomide and Elranatamab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 20 sitesSpain
- Study dates
- 1 Nov 2026to Dec 2032
- 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 adhere/comply with visit schedule and other protocol requirements.
- Patient must be able to understand the study procedures. c. Patients aged ≥18 years at the time of signing the informed consent form. d. Patients have documented diagnosis of MM according to the IMWG criteria (Lancet Oncol 2014).
- Patients have a relapsed MM who have previously received treatment with at least one line of antimyeloma therapy.
- Patients must have documented disease progression during or after their last antimyeloma regimen.
- Patients must have received prior treatment with a lenalidomide-containing regimen and must be intolerant or refractory to it, defined as occurrence of disease progression on lenalidomide or within 60 days after the last dose of treatment to lenalidomide.
- Patient must have a measurable disease, defined as follows:
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- Serum monoclonal protein (M-protein) ≥0,5 g/dl by serum protein electrophoresis (sPEP) or
- Urine light-chain excretion ≥200 mg/24-hour urine collection by urine protein electrophoresis (uPEP) or
- Serum free light-chain (sFLC) levels >100 mg/L (10 mg/dL) involved light chain and an abnormal kappa/lambdda FLC ratio (for patients whose disease is only measurable by serum FLC) i. Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2.
- All prior relevant treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0 must be ≤grade 1 at the time of enrolment.
- Reproductive Status
- Individuals of childbearing potential (IOCBP) must agree and adhere to all testing and contraception requirements for elranatamab based on SmPC and/or IB, and in the mezigdomide Clinical Trial Pregnancy Risk Awareness Checklist. IOCBPs must either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with 2 effective forms of contraception without interruption: 28 days prior to starting study intervention, during treatment (including dose interruptions), and for at least 28 days after the last dose of mezigdomide** or for at least 4 months (or 150 days) following last elranatamab dose whichever is longer.
- Male participants must practice true abstinence* (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant individual or an IOCBP while participating in the study, during dose interruptions and for at least 28 days after the last dose of mezigdomide, or for at least 4 months (or 150 days) following last elranatamab dose whichever is longer, even if he has undergone a successful vasectomy.
- True Abstinence is acceptable when this is in line with the preferred and usual lifestyle of the individual. Periodic abstinence (eg, calendar, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
- Male participants must agree to refrain from donating semen or sperm while taking mezigdomide or during dose interruptions and that they will not donate semen or sperm for at least 28 days after the last dose of mezigdomide.
- Females must agree to refrain from donating eggs and breastfeeding a baby while taking mezigdomide, during dose interruptions and for 28 days after the last dose of mezigdomide.
- Participants must agree to refrain from donating blood while on study treatment, during dose interruptions, and for at least 28 days following the last dose of Mezigdomide or for 4 months (or 150 days) following last dose of elranatamab, whatever happens later.
Who cannot join
- Any serious medical condition or psychiatric illness that would interfere in understanding of the informed consent form.
- Other plasma cell disorders/associated syndromes, e.g. plasma cell leukemia, POEMS, amyloidosis
- Prior therapy with mezigdomide or any BCMA bispecific agent. Prior therapy with a BCMA-targeted CAR T-cell therapy or ADC are allowed if >6 months have elapsed from the last dose.
- Patients with non-adequate hematological and/or non-hematological parameters defined as the following laboratory abnormalities:
- Absolute neutrophil count (ANC) <1 x109/L without previous granulocyte colony-stimulating factor G-CSF support in the last 7 days prior to screening blood count.
- Platelet count <75 x109/L without previous platelet transfusions in the last 7 days prior to screening blood count.
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- Hemoglobin <8.0 g/dl (Erythropoietin or RBC transfusions allowed).
- Calculated or measured creatinine clearance / estimated glomerular filtration rate (eGFR) <30 mL/min (calculated from the Cockcroft and Gault formula) (APPENDIX 5) or requiring dialysis.
- Serum aspartate transaminase (AST): > 2.5 x the upper limit of normal (ULN).
- Serum alanine transaminase (ALT): > 2.5 x ULN.
- Serum total bilirubin: > 2 x ULN
- Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L).
- Left ventricular ejection fraction (LVEF) <50%.
- The following relevant diseases or adverse clinical conditions:
- Uncontrolled cardiac arrhythmias (i.e., requiring a change in medication within the last 3 months or a hospital admission within the past 6 months) or clinically significant electrocardiogram abnormalities such as 2nd degree (Type II) or 3rd degree atrioventricular (AV) block.
- History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 12 months before screening.
- Class III or IV heart failure as defined by the New York Heart Association functional classification system [NYHA, 1994].
- Uncontrolled arterial hypertension (defined as an average systolic blood pressure ≥ 160 mmHg or diastolic ≥ 100 mmHg despite optimal treatment).
- History of significant neurological or psychiatric disorders.
- Ongoing Grade 2 or higher peripheral sensory or motor neuropathy, history of Guillain Barre Syndrome (GBS) or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy.
- Active infection requiring antibiotic, antiviral, or antifungal treatment.
- Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis)
- Uncontrolled endocrine diseases (i.e., diabetes mellitus, hypothyroidism, or hyperthyroidism) (i.e., requiring relevant changes in medication within the last month, or hospital admission within the last 3 months).
- Patient is known to be positive for human immunodeficiency virus (HIV), chronic or active hepatitis B, active hepatitis A, or active hepatitis C. In case of doubt, viral load must be negative.
- Administration of live or live-attenuated vaccines within 30 days prior to the day 1 of cycle 1.
- Prior history of neoplastic disease/malignancies other than MM in the last 5 years (except for basal cell carcinoma, skin epithelioma or carcinoma in situ of any site [i.e., breast, cervix]).
- Use of any antimyeloma therapy within 14 days prior to day 1 of cycle 1.
- Stem cell transplant within 12 weeks prior to enrolment, active GVHD or active immunosuppressive therapy for GVHD.
- Radiation therapy, other than local palliative therapy, for myeloma associated bone lesions within 14 days prior to day 1 of cycle 1.
- Major surgery 14 days prior to initiating study therapy / prior to day 1 of cycle 1.
- Patient has a known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to mezigdomide or drugs chemically related to mezigdomide, or any of the excipients contained in the formulation of the study treatment.
- Participant has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to other bispecific antibodies.
- Any serious medical condition that places the subject at an unacceptable risk if he or she participates in this study;
- Subjects with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis and lupus, that likely need additional steroid or immunosuppressive treatments in addition to the study treatment.
- Women who are pregnant or breastfeeding, or who intends to become pregnant during participation in the study, and men and women of reproductive potential who are not using effective contraceptive methods (double barrier method, intrauterine device, oral contraception).
- Patient is simultaneously enrolled in other interventional clinical trial.
Trial locations and contacts
20 sites in 1 country. Contact the study team or a site near you to ask about taking part.
20 sites in 1 country
Spain20 sites
Complejo Hospitalario de Albacete
Albacete, 02006
Hospital General Universitario Dr. Balmis
Alicante
Hospital Universitari Germans Trias i Pujol (ICO Badalona)
Badalona
H. Moises Broggi
Barcelona
Hospital Clínic de Barcelona
Barcelona
Hospital de Cabueñes
Gijón
H. Un. Virgen de las Nieves
Granada
C. H. U. de Gran Canaria Dr. Negrín
Las Palmas de Gran Canaria
Complejo Hospitalario Lucus Augusti
Lugo
Hospital Doce de Octubre
Madrid, 28041
C. H. Gregorio Marañón
Madrid
Complejo Hospital Costa Del Sol (Ivcs)
Málaga
H. Un. Virgen de la Arrixaca
Murcia
Hospital Central de Asturias
Oviedo
Hospital Son Llatzer
Palma de Mallorca
Clínica Universidad de Navarra (CUN)
Pamplona
Hospital Clínico Universitario Salamanca
Salamanca, 37007
H. Universitario Marqués de Valdecilla
Santander
Hospital Universitari i Politecnic la Fe
Valencia
H. U. Txagorritxu
Vitoria-Gasteiz
About this study
Official title: Multicenter, Open Label, Phase II Clinical Trial Evaluating the Combination of Elranatamab With Mezigdomide and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma
The goal of this clinical trial is to learn if the drug combination Elranatamab plus Mezigdomide plus Dexametahsone works to cure patients with relapsed/refractory multiple myeloma.
The main questions it aims to answer are:
Read more
Do participants receiving Elranatamab plus Mezigdomide plus Dexametahsone achieve optimal treatment response by showing negative minimal residual disease at the end of treatment?
By evaluating the incidence of adverse events and severe adverse events, is this drug combination tolerable for participants?
All participants will receive 1 cycle of Elranatamab plus Dexamethasone followed by 5 cycles of Elranatamab plus Mezigdomide plus Dexamethasone, and 6 cycles of Elranatamab plus Mezigdomide. At this timepoint (end of cycle 12), the level of minimal residual disease will be assessed to decide if patients receive Mezigdomide alone as maintenance (for patients with negative minimal residual disease), or continue reciving Elranatamab plus Mezigdomide.
Read the detailed description
This is a open-label, phase II clinical trial in which participants with relapsed or refractory multiple myeloma will receive a drug combination of Elranatamab plus Mezigdomide plus Dexametahsone to evaluate the proportion of patients who achieve negative minimal residual disease (defined by the presence of less than 1 tumoral cell out of 100.000 healthy hematopoietic cells). In additon, the tolerability of this drug combination will be assessed by recording the incidence of adverse and severe adverse events.
All participants will receive 1 cycle of Elranatamab plus Dexamethasone followed by 5 cycles of Elranatamab plus Mezigdomide plus Dexamethasone, and 6 cycles of Elranatamab plus Mezigdomide. At this timepoint (end of cycle 12), the level of minimal residual disease will be assessed to decide if patients receive Mezigdomide alone as maintenance (for patients with negative minimal residual disease) until unacceptable toxicity, disease progression, patient withdrawal, loss of follow-up, end of study, or death, whichever occurs first; or continue reciving Elranatamab plus Mezigdomide (for patients with positive minimal residual disease) until unacceptable toxicity, disease progression, patient withdrawal, loss of follow-up, end of study, or death, whichever occurs first.
In those participants receiving Mezigdomide as maintenance therapy from cycle 13 onwards (good responders) who show biological disease progression (according to the International Myeloma Working Group, IMWG) or positivization of minimal resdual disease, Elranatamab will be introduced to the Mezigdomide maintenance therapy.
- Being tested
- Dexamethasone, Mezigdomide, Elranatamab
- Keywords
- Elranatamab, Mezigdomide, Dexamethasone, minimal residual disease, Refractory Multiple Myeloma, Relapse Multiple Myeloma
- Medical subject headings
- Neoplasm, Residual, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
Oral at a dose of 20 mg/day (≤ 75 years old) or 10 mg/day (>75 years old) weekly from cycle 1 to cycle 6.
MezigdomideDrug
Oral at a dose of 0.6 mg daily on days 1 to 21 of the 28-day cycle from C2 onwards (not in C1).
ElranatamabDrug
Subcutaneous Elranatamab willl be given as follows:
- Cycle 1: day1 (step-up dose 12 mg), day4 (step-up dose 32 mg), day8 (target dose 76 mg), day15 (76 mg), and D22 (76 mg) of a 28-day cycle.
- Cycles 2 and 3: day1 and day15 (76 mg) of each 28-day cycle.
- From C4 onwards: day1 (76 mg) of each 28-day cycle.
- From C13 onwards: those patients who have achieved MRD negativity sustained for at least 3 cycles, will discontinue elranatamab and will continue with mezigdomide alone as maintenance.
In those patients who discontinue elranatamab due to sustained MRD negativity, it will be reintroduced as from the cycle 2 in case of biological progression (IMWG criteria) or positivization of MRD.
| Study group | Role | What they receive |
|---|---|---|
| Negative minimal residual disease at end cycle 12 | Active comparator | All participants will receive Elranatamab, Mezigdominde and Dexametahsone in 28-day cycles as follows:
* Oral Mezigdomide: dose of 0.6 mg daily on days 1 to 21 of each cycle (from cycle 2 onwards).
* Oral Dexamethasone: dose of 20 mg/day (≤ 75 years old) or 10 mg/day (>75 years old) from cycle 1 to 6.
* Subcutaneous Elranatamab:
Cycle 1: day1 (step-up dose 12 mg), day4 (step-up dose 32 mg), day8 (target dose 76 mg), day15 (76 mg), and day22 (76 mg).
Cycles 2 and 3: day1 and day15 (76 mg) of each 28-day cycle. From cycle 4 onwards: day1 (76 mg). From Cycle 13 onwards, participants will discontinue elranatamab and will continue with mezigdomide alone.
In those patients who discontinue elranatamab due to sustained MRD negativity, Elranatamab will be reintroduced as from the cycle 2 in case of biological progression (IMWG criteria) or positivization of MRD. Receives: Drug: Dexamethasone; Drug: Mezigdomide; Drug: Elranatamab |
| Positive minimal residual disease et end cycle 12 | Active comparator | All participants will receive Elranatamab, Mezigdominde and Dexametahsone in 28-day cycles as follows:
* Oral Mezigdomide: dose of 0.6 mg daily on days 1 to 21 of each cycle (from cycle 2 onwards).
* Oral Dexamethasone: dose of 20 mg/day (≤ 75 years old) or 10 mg/day (>75 years old) from cycle 1 to 6.
* Subcutaneous Elranatamab will be given as follows:
* Cycle 1: day1 (step-up dose 12 mg), day4 (step-up dose 32 mg), day8 (target dose 76 mg), day15 (76 mg), and day22 (76 mg).
* Cycles 2 and 3: day1 and day15 (76 mg) of each 28-day cycle.
* From cycle 4 onwards: day1 (76 mg).
* From Cycle 13 onwards, patients with positive minimal residual disease will keep receiving Elranatamab as from cycle 4 plus Mezigdomide with above indicated dose. Receives: Drug: Dexamethasone; Drug: Mezigdomide; Drug: Elranatamab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients achieving minimal residual disease (MRD) negativity.
To evaluate the percentage of participants achieving negative MRD. Negative MRD is defined as the presence of less than 1 tumour cell among 100,000 healthy hematopoietic cells by Next Generation Flow Cytometry in bone marrow, according to the IMWG criteria.
Measured: 5 years
Secondary outcomes (17)
Proportion of participants showing sustained MRD negativity at 24 months
Percentage of participants showing sustained MRD negativity at 24. Negative MRD is defined as the presence of less than 1 tumour cell among 100,000 healthy hematopoietic cells by Next Generation Flow Cytometry in bone marrow, according to the IMWG criteria.
Measured: 5 years
Proportion of participants showing MRD negativity after early rescue intervention with elranatamab in patients on mezigdomide alone after C12.
Those participants showing good initial treatment response (allocated in the MRD negative at end cycle 12 intervention arm and receiving Mezigdomide maintenance therapy) who show MRD positivization during maintenance therapy with Mezigdomide alone, will be evaluated to detect the rate of MRD negativization after early rescue intervention with Elranatamab.
Negative MRD is defined as the presence of less than 1 tumour cell among 100,000 healthy hematopoietic cells by Next Generation Flow Cytometry in bone marrow, according to the IMWG criteria.
Measured: 5 years
To evaluate the Complete Response rate to elranatamab in combination with mezigdomide and dexamethasone, based on confirmed response according to the IMWG criteria.
Defined as the percentage of patients who show the following 4 parameters: i) absence of monoclonal protein in serum, ii) absence of monoclonal protein in urine, iii) disappearance of any previous soft tissue plasmacytomas, iv) less than 5% plasma cells in bone marrow aspirates or biopsy
Measured: 5 years
To evaluate the Very Good Partial Response rate to elranatamab in combination with mezigdomide and dexamethasone, based on confirmed response according to the IMWG criteria.
Defined as having the following conditions: i) >90% reduction of M protein in serum, ii) less than 100 mg of M protein un urine within 24 hours, iiI) no presence of plasmocitomas.
Measured: 5 years
To evaluate the Partial Response rate to elranatamab in combination with mezigdomide and dexamethasone, based on confirmed response according to the IMWG criteria.
Defined as havong the following: i) >50% reduction of serum M protein, ii) <200mg of M-protein in urine in 24-hour.
Measured: 5 years
To evaluate the Minimal Response rate to elranatamab in combination with mezigdomide and dexamethasone, based on confirmed response according to the IMWG criteria.
Defined as showing a 25% to 49% reduction in serum monoclonal M-protein alongside a 50% to 89% reduction in 24-hour urinary M-protein.
Measured: 5 years
To evaluate the Stable Disease rate to elranatamab in combination with mezigdomide and dexamethasone, based on confirmed response according to the IMWG criteria.
Defined as >25% reduction in serum monoclonal M-protein alongside a >50% reduction in 24-hour urine M-protein.
Measured: 5 years
To evaluate the Duration of Response with Elranatamab in combination with mezigdomide and dexamethasone.
Defined as the time from the achievement of at least a Partial Response until the earliest date of documented disease progression by IMWG criteria.
Measured: 5 years
To evaluate the Progression-free Survival with Elranatamab in combination with mezigdomide and dexamethasone.
Defined as the time from the date of Elranatamab treatment initiation until the earliest date of documented disease progression by IMWG criteria or death due to any cause.
Measured: 5 years
To evaluate the Overall Survival with Elranatamab in combination with mezigdomide and dexamethasone.
Defined as the time from the date of Elranatamab treatment initiation until the date of death due to any cause.
Measured: 5 years
Incidence of Adverse Events (AE) related with the treatment with elranatamab in combination with mezigdomide and dexamethasone
Number of adverse events registered within the clinical trial study period related with the treatment with elranatamab in combination with mezigdomide and dexamethasone.
Adverse Events are defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure, and are evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
Measured: 5 years
Discontinuation of therapy due to Adverse Event related with the treatment with elranatamab in combination with mezigdomide and dexamethasone
Defined as the percentage of patients discontinuing therapy due to Adverse Events of treatment with elranatamab in combination with mezigdomide and dexamethasone
Measured: 5 years
Dose modifications due to Adverse Events related with treatment with elranatamab in combination with mezigdomide and dexamethasone
Defined as the percentage of patients requiring dose modifications due to Adverse Events of treatment with elranatamab in combination with mezigdomide and dexamethasone
Measured: 5 years
Incidence of Severe Adverse Events of treatment with elranatamab in combination with mezigdomide and dexamethasone
Number of severe adverse events, defined as:
Any untoward medical occurrence that, at any dose;
- Results in death;
- Is life threatening;
- Requires inpatient hospitalization* or prolongation of existing hospitalization;
- Results in persistent or significant disability/incapacity;
- Is a congenital anomaly/birth defect;
- Is an important medical event;
- Is associated with liver injury and impaired liver function defined as: ALT ≥3 x ULN and total bilirubina ≥2 x ULN (>35% direct), or ALT ≥3 x ULN and INRb >1.5.
- Any suspected transmission of any infectious agent via a product (medically significant)
Measured: 5 years
Changes in laboratory analytes from the hematology and blood chemistry panel related to treatment with elranatamab in combination with mezigdomide and dexamethasone
Defined as the number of the changes in laboratory analytes from the hematology and blood chemistry panel related to treatment with elranatamab in combination with mezigdomide and dexamethasone
Measured: 5 years
Incidence of deaths related with the treatment with elranatamab in combination with mezigdomide and dexamethasone
Defined as the number of deaths related with the treatment with elranatamab in combination with mezigdomide and dexamethasone
Measured: 5 years
Primary cause of death of treatment with elranatamab in combination with mezigdomide and dexamethasone
Defined as the description of the cause of death related with the treatment with elranatamab in combination with mezigdomide and dexamethasone
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2026
- Study start1 Nov 2026 (estimated)
- Primary completionDec 2031 (estimated)
- Study completionDec 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple Myeloma RefractoryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- PETHEMA Foundation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Enrique Ocio, PhD, Principal investigator, Hospital Universitario Marqués de ValdecillaAlbert Oriol, PhD, Principal investigator, Institut Català d'Oncologia - Hospital Germans Trias i Pujol
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07901868
- Sponsor's protocol ID
- GEM-MeziDEL
- Acronym
- GEM-MeziDEL
- Status last verified
- Oct 2026
- First submitted
- 17 Oct 2026
- Last updated
- 28 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter, Open Label, Phase II Clinical Trial Evaluating the Combination of Elranatamab With Mezigdomide and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT07901868
- Acronym / sponsor ID
- GEM-MeziDEL / GEM-MeziDEL
- Keywords
- Elranatamab, Mezigdomide, Dexamethasone, minimal residual disease, Refractory Multiple Myeloma, Relapse Multiple Myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- PETHEMA FoundationUniversity, hospital or other
- Study start
- 1 Nov 2026 (estimated)
- Primary completion
- Dec 2031 (estimated)
- Study completion
- Dec 2032 (estimated)
- First posted
- 28 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to learn if the drug combination Elranatamab plus Mezigdomide plus Dexametahsone works to cure patients with relapsed/refractory multiple myeloma.
The main questions it aims to answer are:
Do participants receiving Elranatamab plus Mezigdomide plus Dexametahsone achieve optimal treatment response by showing negative minimal residual disease at the end of treatment?
By evaluating the incidence of adverse events and severe adverse events, is this drug combination tolerable for participants?
All participants will receive 1 cycle of Elranatamab plus Dexamethasone followed by 5 cycles of Elranatamab plus Mezigdomide plus Dexamethasone, and 6 cycles of Elranatamab plus Mezigdomide. At this timepoint (end of cycle 12), the level of minimal residual disease will be assessed to decide if patients receive Mezigdomide alone as maintenance (for patients with negative minimal residual disease), or continue reciving Elranatamab plus Mezigdomide.
Detailed description
This is a open-label, phase II clinical trial in which participants with relapsed or refractory multiple myeloma will receive a drug combination of Elranatamab plus Mezigdomide plus Dexametahsone to evaluate the proportion of patients who achieve negative minimal residual disease (defined by the presence of less than 1 tumoral cell out of 100.000 healthy hematopoietic cells). In additon, the tolerability of this drug combination will be assessed by recording the incidence of adverse and severe adverse events.
All participants will receive 1 cycle of Elranatamab plus Dexamethasone followed by 5 cycles of Elranatamab plus Mezigdomide plus Dexamethasone, and 6 cycles of Elranatamab plus Mezigdomide. At this timepoint (end of cycle 12), the level of minimal residual disease will be assessed to decide if patients receive Mezigdomide alone as maintenance (for patients with negative minimal residual disease) until unacceptable toxicity, disease progression, patient withdrawal, loss of follow-up, end of study, or death, whichever occurs first; or continue reciving Elranatamab plus Mezigdomide (for patients with positive minimal residual disease) until unacceptable toxicity, disease progression, patient withdrawal, loss of follow-up, end of study, or death, whichever occurs first.
In those participants receiving Mezigdomide as maintenance therapy from cycle 13 onwards (good responders) who show biological disease progression (according to the International Myeloma Working Group, IMWG) or positivization of minimal resdual disease, Elranatamab will be introduced to the Mezigdomide maintenance therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Negative minimal residual disease at end cycle 12 | Active comparator | Drug: Dexamethasone, Drug: Mezigdomide, Drug: ElranatamabAll participants will receive Elranatamab, Mezigdominde and Dexametahsone in 28-day cycles as follows: * Oral Mezigdomide: dose of 0.6 mg daily on days 1 to 21 of each cycle (from cycle 2 onwards). * Oral Dexamethasone: dose of 20 mg/day (≤ 75 years old) or 10 mg/day (>75 years old) from cycle 1 to 6. * Subcutaneous Elranatamab: Cycle 1: day1 (step-up dose 12 mg), day4 (step-up dose 32 mg), day8 (target dose 76 mg), day15 (76 mg), and day22 (76 mg). Cycles 2 and 3: day1 and day15 (76 mg) of each 28-day cycle. From cycle 4 onwards: day1 (76 mg). From Cycle 13 onwards, participants will discontinue elranatamab and will continue with mezigdomide alone. In those patients who discontinue elranatamab due to sustained MRD negativity, Elranatamab will be reintroduced as from the cycle 2 in case of biological progression (IMWG criteria) or positivization of MRD. |
| Positive minimal residual disease et end cycle 12 | Active comparator | Drug: Dexamethasone, Drug: Mezigdomide, Drug: ElranatamabAll participants will receive Elranatamab, Mezigdominde and Dexametahsone in 28-day cycles as follows: * Oral Mezigdomide: dose of 0.6 mg daily on days 1 to 21 of each cycle (from cycle 2 onwards). * Oral Dexamethasone: dose of 20 mg/day (≤ 75 years old) or 10 mg/day (>75 years old) from cycle 1 to 6. * Subcutaneous Elranatamab will be given as follows: * Cycle 1: day1 (step-up dose 12 mg), day4 (step-up dose 32 mg), day8 (target dose 76 mg), day15 (76 mg), and day22 (76 mg). * Cycles 2 and 3: day1 and day15 (76 mg) of each 28-day cycle. * From cycle 4 onwards: day1 (76 mg). * From Cycle 13 onwards, patients with positive minimal residual disease will keep receiving Elranatamab as from cycle 4 plus Mezigdomide with above indicated dose. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Patient is, in the investigator's opinion, willing and able to adhere/comply with visit schedule and other protocol requirements.
- Patient must be able to understand the study procedures. c. Patients aged ≥18 years at the time of signing the informed consent form. d. Patients have documented diagnosis of MM according to the IMWG criteria (Lancet Oncol 2014).
- Patients have a relapsed MM who have previously received treatment with at least one line of antimyeloma therapy.
- Patients must have documented disease progression during or after their last antimyeloma regimen.
- Patients must have received prior treatment with a lenalidomide-containing regimen and must be intolerant or refractory to it, defined as occurrence of disease progression on lenalidomide or within 60 days after the last dose of treatment to lenalidomide.
Key exclusion criteria (36 listed)
- Any serious medical condition or psychiatric illness that would interfere in understanding of the informed consent form.
- Other plasma cell disorders/associated syndromes, e.g. plasma cell leukemia, POEMS, amyloidosis
- Prior therapy with mezigdomide or any BCMA bispecific agent. Prior therapy with a BCMA-targeted CAR T-cell therapy or ADC are allowed if >6 months have elapsed from the last dose.
- Patients with non-adequate hematological and/or non-hematological parameters defined as the following laboratory abnormalities:
- Left ventricular ejection fraction (LVEF) <50%.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexamethasoneOral at a dose of 20 mg/day (≤ 75 years old) or 10 mg/day (>75 years old) weekly from cycle 1 to cycle 6. | Drug | Negative minimal residual disease at end cycle 12, Positive minimal residual disease et end cycle 12 |
| MezigdomideOral at a dose of 0.6 mg daily on days 1 to 21 of the 28-day cycle from C2 onwards (not in C1). | Drug | Negative minimal residual disease at end cycle 12, Positive minimal residual disease et end cycle 12 |
| ElranatamabSubcutaneous Elranatamab willl be given as follows: * Cycle 1: day1 (step-up dose 12 mg), day4 (step-up dose 32 mg), day8 (target dose 76 mg), day15 (76 mg), and D22 (76 mg) of a 28-day cycle. * Cycles 2 and 3: day1 and day15 (76 mg) of each 28-day cycle. * From C4 onwards: day1 (76 mg) of each 28-day cycle. * From C13 onwards: those patients who have achieved MRD negativity sustained for at least 3 cycles, will discontinue elranatamab and will continue with mezigdomide alone as maintenance. In those patients who discontinue elranatamab due to sustained MRD negativity, it will be reintroduced as from the cycle 2 in case of biological progression (IMWG criteria) or positivization of MRD. | Drug | Negative minimal residual disease at end cycle 12, Positive minimal residual disease et end cycle 12 |
Primary outcome
Proportion of patients achieving minimal residual disease (MRD) negativity.
Time frame: 5 years
To evaluate the percentage of participants achieving negative MRD. Negative MRD is defined as the presence of less than 1 tumour cell among 100,000 healthy hematopoietic cells by Next Generation Flow Cytometry in bone marrow, according to the IMWG criteria.
17 secondary outcomes
Proportion of participants showing sustained MRD negativity at 24 months
Time frame: 5 years
Proportion of participants showing MRD negativity after early rescue intervention with elranatamab in patients on mezigdomide alone after C12.
Time frame: 5 years
To evaluate the Complete Response rate to elranatamab in combination with mezigdomide and dexamethasone, based on confirmed response according to the IMWG criteria.
Time frame: 5 years
To evaluate the Very Good Partial Response rate to elranatamab in combination with mezigdomide and dexamethasone, based on confirmed response according to the IMWG criteria.
Time frame: 5 years
To evaluate the Partial Response rate to elranatamab in combination with mezigdomide and dexamethasone, based on confirmed response according to the IMWG criteria.
Time frame: 5 years
To evaluate the Minimal Response rate to elranatamab in combination with mezigdomide and dexamethasone, based on confirmed response according to the IMWG criteria.
Time frame: 5 years
To evaluate the Stable Disease rate to elranatamab in combination with mezigdomide and dexamethasone, based on confirmed response according to the IMWG criteria.
Time frame: 5 years
To evaluate the Duration of Response with Elranatamab in combination with mezigdomide and dexamethasone.
Time frame: 5 years
To evaluate the Progression-free Survival with Elranatamab in combination with mezigdomide and dexamethasone.
Time frame: 5 years
To evaluate the Overall Survival with Elranatamab in combination with mezigdomide and dexamethasone.
Time frame: 5 years
Incidence of Adverse Events (AE) related with the treatment with elranatamab in combination with mezigdomide and dexamethasone
Time frame: 5 years
Discontinuation of therapy due to Adverse Event related with the treatment with elranatamab in combination with mezigdomide and dexamethasone
Time frame: 5 years
Dose modifications due to Adverse Events related with treatment with elranatamab in combination with mezigdomide and dexamethasone
Time frame: 5 years
Incidence of Severe Adverse Events of treatment with elranatamab in combination with mezigdomide and dexamethasone
Time frame: 5 years
Changes in laboratory analytes from the hematology and blood chemistry panel related to treatment with elranatamab in combination with mezigdomide and dexamethasone
Time frame: 5 years
Incidence of deaths related with the treatment with elranatamab in combination with mezigdomide and dexamethasone
Time frame: 5 years
Primary cause of death of treatment with elranatamab in combination with mezigdomide and dexamethasone
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Enrique Ocio, PhD principal investigator
Hospital Universitario Marqués de Valdecilla
Albert Oriol, PhD principal investigator
Institut Català d'Oncologia - Hospital Germans Trias i Pujol
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dexamethasone, Mezigdomide and Elranatamab in people with Multiple Myeloma Refractory and Multiple Myeloma in Relapse, run by PETHEMA Foundation at 20 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 17 inclusion and 36 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: opening soon, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 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?
Contact Alfonso Santiago, PhD (+34916266232, gerencia@fundacionpethema.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients achieving minimal residual disease (MRD) negativity. (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Oct 2026.