Clinical trial NCT06183489: Use of Elranatamab in Patients With High-risk Smoldering Multiple Myeloma
Official title: A Multi-center, Open-label, Phase 2 Study of Elranatamab in Patients With High-risk Smoldering Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Smoldering Multiple Myeloma
Keywords: high-risk smoldering Multiple Myeloma
Elranatamab
Lead sponsor: European Myeloma Network B.V.
Sponsor class: NETWORK
Collaborators: name: Pfizer
First posted: 2023-12-27
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a multicenter, single arm, open-label, Phase 2 study in high risk smoldering myeloma patients. The primary objective is to determine the efficacy of Elranatamab in patients with previously untreated high-risk SMM. The key-secondary objective is to determine the safety of Elranatamab in patients with previously untreated high-risk SMM.


Eligibility criteria: Inclusion Criteria:

1. \>18 years of age
2. Diagnosis of SMM for ≤5 years with measurable disease, defined as serum M protein:

   ≥1g/dL or urine M protein ≥200 mg/24 hours or involved serum FLC ≥100 mg/Land abnormal serum FLC ratio.
3. BMPCs ≥10% and \<60%
4. Presence of at least 2 high risk factors, including

   1. Serum M protein ≥2 g/dL,
   2. BMPC \>20%
   3. Serum involved/uninvolved FLC ratio \> 20
5. ECOG performance status score of 0 or 1
6. Subjects must meet the following laboratory parameters, per laboratory reference range (performed at most 15 days before cycle 1 day 1)

   1. Absolute neutrophil count ≥1.0 x 109/L (ie, ≥1000/μL)
   2. Platelet count ≥75 x 109/L
   3. Aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN)
   4. Alanine aminotransferase (ALT) ≤2.5 x ULN
   5. Total bilirubin ≤1.5 x ULN, except in subjects with congenital bilirubinemia,such as Gilbert syndrome (in which case direct bilirubin ≤2.0 x ULN is required)
7. Subject must sign an informed consent form (ICF) or their legally acceptable representative must sign indicating that he or she understands the purpose of, and procedures required for the study and is willing to participate in the study.
8. Women of childbearing potential must have a negative serum or urine pregnancy test at screening and before starting study drug. They must commit to continued abstinence from heterosexual intercourse or begin 2 acceptable methods of birth control (One highly effective method and one additional effective method) used at the same time, and continuing for at least 5 months after the last dose of Elranatamab. Women must also agree to notify pregnancy during the study.

Exclusion Criteria:

1. Previous therapy with any systemic therapy for multiple myeloma.
2. Evidence of any of the following calcium, renal failure, anemia, bone lesions (CRAB) criteria or Myeloma Defining Events (SLiM CRAB) detailed below (attributable to the participants SMM involvement):

   1. Increased calcium levels: Corrected serum calcium \>1 mg/dL above the ULN or \>11 mg/dL
   2. Renal insufficiency: Determined by glomerular filtration rate (GFR) \<40 mL/min/1.73 m² (Modification of Diet in Renal Disease \[MDRD\] Formula) or serum creatinine \>2 mg/dL
   3. Anemia (hemoglobin 2 g/dL below lower limit of normal or \<10 g/dL or both) transfusion support or concurrent treatment with erythropoietin stimulating agents is not permitted
   4. ≥ 1 bone lytic lesion
   5. BMPCs ≥60%
   6. Serum involved/uninvolved FLC ratio ≥100 and an involved FLC ≥100mg/L
   7. Whole body magnetic resonance imaging (WB-MRI) or positron emission tomography-computed tomography (PET-CT) with more than 1 bone focal lesion (≥5 mm in diameter)
3. Diagnosis of primary amyloidosis, POEMS syndrome, monoclonal gammopathy of undetermined significance, symptomatic multiple myeloma, or solitary plasmacytoma.
4. Subject has a diagnosis of Waldenström's macroglobulinemia, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.
5. Subject has had plasmapheresis within 14 days of elegibility confirmation.
6. Myocardial infarction within 6 months prior to enrolment according to NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
7. Ongoing Grade 2 or higher peripheral sensory/motor peripheral neuropathy (PN), history of GBS or GBS variants, or history of grade 3 or higher peripheral motor polyneuropathy
8. Subject has had major surgery within 2 weeks before elegibility confirmation or will not have fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study.
9. Clinically relevant active infection or serious co-morbid medical conditions
10. Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical, breast or prostate cancer free of disease since 5 years.
11. Female subject who is pregnant or breast-feeding
12. Serious medical or psychiatric illness likely to interfere with participation in study
13. Uncontrolled diabetes mellitus
14. Known HIV infection; Known active hepatitis B or C viral infection; known active COVID-19/SARS-CoV-2 infection
15. Live attenuated vaccine administered within 4 weeks of the first dose of study intervention
16. Ongoing treatment with corticosteroids : dose \>10mg prednisone etc.
17. Person under guardianship, trusteeship or deprived of freedom by a judicial or administrative decision

Primary outcomes:
measure: Complete Remission (CR) rate
timeFrame: average 24 weeks
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: average 24 weeks
measure: MRD-negative CR (MRD_CR)
timeFrame: average 24 weeks
measure: Progression-free survival (PFS)
timeFrame: time from the date of 1st dose to to the date of disease progression or death, assed up to 4 years after last dose
measure: Time to progression (TTP)
timeFrame: time from the date of 1st dose to progression or death, assed up to 4 years after last dose
measure: Progression free survival 2 (PFS2)
timeFrame: time from the date of 1st dose to progression on the next line of treatment or death,assed up to 4 years after last dose
measure: Overall survival (OS)
timeFrame: time from the date of 1st dose to date of death, assed up to 4 years after last dose
measure: Time to response (TTR)
timeFrame: time frrom the date of 1st dose to the first documented response
measure: Change in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core module (EORTC QLQ-C30)
timeFrame: from screening, cycle 1 and every 3 cycles there after up to end of treatment and 28 days after last treatment
measure: Change in EORTC QLQ- 20-item Multiple Myeloma module (MY-20) score
timeFrame: from screening, cycle 1 and every 3 cycles there after up to end of treatment and 28 days after last treatment
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: La Roche-sur-Yon
country: France
facility: CHD Vendée
city: Lille
country: France
facility: CHRU de Lille - Hopital Claude Huriez
city: Montpellier
country: France
facility: CHU Saint Eloi Département d'Hématologie Clinique
city: Nantes
country: France
facility: CHU Hôtel-Dieu, 1, place Alexis Ricordeau, 44093 NANTES Cedex 1, FRANCE
city: Nice
country: France
facility: CHU NICE - Hôpital Archet
city: Poitiers
country: France
facility: CHU Poitiers - Pôle régional de Cancérologie
city: Tours
country: France
facility: CHRU Hôpital Bretonneau
city: Athens
country: Greece
facility: Alexandra General Hospital -Department of Clinical Therapeutics N.K. Univ. of Athens
city: Bari
country: Italy
facility: AOU Consorziale Policlinico di Bari
city: Bergamo
country: Italy
facility: A.O. Papa Giovanni XXIII
city: Firenze
country: Italy
facility: A.O.U. Careggi
city: Genova
country: Italy
facility: A.O.U. Policlinico S. Martino - Ematologia
city: Meldola
country: Italy
facility: Meldola-Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.)
city: Messina
country: Italy
facility: Ospedale Papardo
city: Novara
country: Italy
facility: A.O.U. Maggiore della Carità Novara
city: Padova
country: Italy
facility: A.O. di Padova
city: Parma
country: Italy
facility: A.O.U. di Parma - U.O Ematologia e CTMO
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico S. Matteo
city: Roma
country: Italy
facility: Ospedale Santo Spirito Ospedale -Azienda Sanitaria Locale Di Pescara
city: Udine
country: Italy
facility: Clinica Ematologica Azienda Sanitaria Universitaria Friuli Centrale
city: Maastricht
country: Netherlands
facility: Maastricht UMC
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Oslo
country: Norway
facility: Oslo Myeloma Center
Study officials:
References: