Trial Title:
Multicenter Phase 2 Study of Subcutaneous Isatuximab Plus Bortezomib, Lenalidomide and Dexamethasone in the Treatment of Newly Diagnosed Transplant Ineligible Multiple Myeloma
NCT ID:
NCT05889221
Condition:
Multiple Myeloma
Myeloma Multiple
Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Conditions: Keywords:
ISATUXIMAB
ISASOCUT
Bortezomib
Lenalidomide
Dexamethasone
VGPR
Study type:
Interventional
Study phase:
N/A
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Other
Intervention name:
Drug and medical device
Description:
Isatuximab will be administered in the hospital by an healthcare professional in the
periumbilical region at a single site, using an investigational device injector;
injection site will be rotated from one administration to the other.
Arm group label:
Combination isatuximab SC, lenalidomide, bortezomib and dexamethasone
Summary:
Isatuximab was developed on a sub-cutaneous (SC) administration format. SC administration
is expected to be more convenient for the patient, with a much shorter duration of
administration compared to the currently approved IV route.
The SC Isatuximab RP2D fixed dose was determined at 1400 mg in a phase1b assessing SC
Isatuximab in combination with pomalidomide and dexamethasone in RRMM patients. A similar
activity and a favorable safety administration profile compared to the IV formulation,
was shown in this trial, as expected (Moreau et al, ASH 2021; Quach et al, ASCO 2022).
This data should be confirmed in the ongoing IRAKLIA/EFC15951 phase 3 study, that
compared in the RRMM, isatuximab plus pomalidomide and dexamethasone IV versus SC.
Whether isatuximab SC, fixed 1400 mg dose, will show similar efficacy and safety profile
as to anti-CD38Rd+V remains to be demonstrated. The investigators have planned to study
the combination of SC isatuximab plus VRd (IsVRd) in patients with NDMM NTE in a phase 2
study across IFM (Intergroupe Francophone du Myeloma) centers in France to compare
indirectly this data to the data obtained from studies that have studied this association
in that population with the IV isatuximab formulation.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Must be able to understand and voluntarily sign an informed consent form
2. Must be able to adhere to the study visit schedule and other protocol requirements
3. Patient able to swallow the various oral treatments
4. Life expectancy > 6 months
5. Subject, male or female, must be at least ≥ 65 years of age
6. Must have a Newly diagnosed Multiple Myeloma requiring therapy (SLiM CRAB criteria)
(see appendix 18.2) 6.1. Monoclonal plasma cells in the bone marrow ≥10% or presence
of a biopsy proven plasmacytoma 6.2. Revised International Myeloma Working Group
diagnostic criteria for multiple myeloma
Myeloma defining events:
- Evidence of end organ damage that can be attributed to the underlying plasma
cell proliferative disorder, specifically: • Hypercalcemia: serum calcium >0.25
mmol/L (>1 mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11
mg/dL) • Renal insufficiency: creatinine clearance ≤40 mL per min† or serum
creatinine ≥177 μmol/L (≥2 mg/dL)
†Measured or estimated by validated equations
- Anemia: hemoglobin value of ≥ 20 g/L below the lower limit of normal, or
hemoglobin value ≤100 g/L
- Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or
PET-CT ‡
- If bone marrow has less than 10% clonal plasma cells, more than one bone
lesion is required to distinguish from solitary plasmacytoma with minimal
marrow involvement
- Any one or more of the following biomarkers of malignancy:
- Clonal bone marrow plasma cell percentage* ≥60%
- Involved/uninvolved serum free light chain ratio ≥100
- >1 focal lesion on MRI studies (Each focal lesion must be 5 mm or more in
size.)
7. Must have measurable disease as defined by any of the following:
Serum monoclonal paraprotein (M-protein) level ≥5 g/L or urine M- protein level ≥200
mg/24 hours; or Serum immunoglobulin free light chain ≥100 mg/L and abnormal serum
immunoglobulin kappa lambda free light chain ratio (any method)*
* The same method must be used along the study for a given patient.
8. Must be nontransplant eligible 8.1. Newly diagnosed and not considered candidate for
high- dose chemotherapy with SCT. 8.2. Subject must have Charlson comorbidity index
≤1 8.3. ECOG ≤2
9. Adequate bone marrow function, documented within 72 hours and without transfusion 72
hours prior to the first intake of investigational product (C1J1) with no growth
factor support (one week), defined as:
- Absolute neutrophils ≥ 1 x109/L,
- Untransfused Platelet count ≥ 75 x109/L,
- Hemoglobin ≥8.5 g/dL.
10. Adequate organ function documented within one week prior to the first intake of
investigational product (C1J1) defined as:
- Serum total bilirubin < 2x upper limit of normal (ULN),
- Creatinine clearance ≥ 30ml/min calculated with MDRD formula,
- Serum SGOT/AST or SGPT/ALT < 3x upper limit of normal (ULN).
11. Person affiliated to the French social security system or equivalent
12. A man who is sexually active with a pregnant woman or a woman of childbearing
potential must agree to use a barrier method of birth control e.g., condom with
spermicidal foam/gel/film/cream/suppository during the study and for at least 5
months after the last dose of treatment, even he has had a vasectomy.
13. A female participant is eligible to participate if she is not pregnant, not
breastfeeding, and at least one of the following conditions applies:
13.1. Not a female of childbearing potential Or 13.2. A FCBP* who must have a
negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL
within 10 - 14 days prior to and again within 24 hours prior to starting study
medication and before each cycle of study treatment.
A FCBP* must understand and agree to continue abstinence from heterosexual
intercourse or to use 2 reliable effective methods of contraception (a very
effective method and an effective additional method) simultaneously without
interruption:
13.2.1. For at least 28 days before starting experimental treatments, 13.2.2.
Throughout the entire duration of experimental treatments, 13.2.3. During dose
interruptions, 13.2.4. And for at least 5 months after the last dose of experimental
treatments.
14. All patients must understand and accept to comply with the conditions of the
Lenalidomide pregnancy prevention plan
Exclusion Criteria :
1. Subject has a diagnosis of primary systemic amyloidosis, monoclonal gammopathy of
undetermined significance, or smouldering multiple myeloma.
2. Subject has a diagnosis of 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.
3. Subject has prior or current systemic therapy or SCT for multiple myeloma, with the
exception of an emergency use of a short course (equivalent of dexamethasone 40
mg/day for a maximum 4 days) of corticosteroids before treatment.
4. Subject has a history of ongoing malignancy (other than multiple myeloma) within 3
years (date of diagnosis of the malignancy) before inclusion in the study treatment
(exceptions are malignancies considered cured with minimal risk of recurrence within
3 years, even though the patient receives treatment).
5. Subject has had radiation therapy within 7 days study treatment*
* unless done for antalgic reason or in case of functional risk for the patient.
6. Subject has had plasmapheresis within 7 days study treatment *
* unless patient disease is still measurable (inclusion criteria n°6) after the
plasmapheresis.
7. Subject is exhibiting clinical signs of meningeal involvement of multiple myeloma.
8. Known to be seropositive for history of human immunodeficiency virus (HIV).
9. Known to have hepatitis B active or uncontrolled infection (positive HBsAg and/or
HBV DNA)
10. Known to have hepatitis C active infection (positive HCV RNA and negative anti-HCV)
11. Subject has any clinically significant medical or psychiatric condition or disease
(e.g., uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) in the
investigator's opinion, would expose the patient to excessive risk or may interfere
with compliance or interpretation of the study results.
12. Subject has active systemic infection and severe infections requiring treatment with
a parenteral administration of antibiotics.
13. Subject has clinically significant cardiac disease, including:
- myocardial infarction within 6 months before study treatment, or an unstable or
uncontrolled disease/condition related to or affecting cardiac function (e.g.,
unstable angina, congestive heart failure, New York Heart Association Class
III-IV)
- uncontrolled cardiac arrhythmia (National Cancer Institute Common Terminology
Criteria for Adverse Events [NCI CTCAE] Version 5 Grade ≥2) or clinically
significant ECG abnormalities or LVEF < 40 % 14. Subject has known allergies,
hypersensitivity, or intolerance to steroids, mannitol, pregelatinized starch,
sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine
hydrochloride, poloxamer 188, sucrose or any of the other components of study
intervention that are not amenable to premedication with steroids and H2
blockers or would prohibit further treatment with these agents, monoclonal
antibodies or human proteins, or their excipients (refer to respective package
inserts or Investigator's Brochure).
15. Known hypersensitivity, allergy to one of the study product (isatuximab,
lenalidomide, bortezomib), dexamethasone, boron or to one of the
excipients. Allergy to bandages or adhesives (acrylic).
16. Acute diffuse infiltrative pneumopathy, pericardial disease 17. Subject
has plasma cell leukemia (according to World Health Organization [WHO]
criterion: ≥20% of cells in the peripheral blood with an absolute plasma
cell count of more than 2 × 109/L) or POEMS syndrome (polyneuropathy,
organomegaly, endocrinopathy, monoclonal protein, and skin changes).
18. Subject is known or suspected of not being able to comply with the study
protocol (e.g., because of alcoholism, drug dependency, or psychological
disorder). Subject has any condition for which, in the opinion of the
investigator, participation would not be in the best interest of the
subject (e.g., compromise the well-being) or that could prevent, limit, or
confound the protocol- specified assessments. Subject is taking any
prohibited medications.
19. Subject has had major surgery within 2 weeks before study treatment or has
not fully recovered from surgery, excluding surgery related to myeloma.
20. Subject has received an investigational drug (including investigational
vaccines) within 14 days or 5 half-lives of the investigational drug prior
to initiation of study intervention, whichever is longer, or used an
invasive investigational medical device within 4 weeks before study
treatment or is currently enrolled in an interventional investigational
study.
21. Persons referred to in Articles L1121-5 to L1121-8 of the CSP 22. Subject
has contraindications to required prophylaxis for deep vein thrombosis and
pulmonary embolism.
23. Incidence of gastrointestinal disease that may significantly alter the
absorption of oral drugs.
Gender:
All
Minimum age:
65 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
CHU Poitiers
Address:
City:
Poitiers
Zip:
86000
Country:
France
Start date:
October 23, 2023
Completion date:
July 1, 2028
Lead sponsor:
Agency:
Poitiers University Hospital
Agency class:
Other
Collaborator:
Agency:
Sanofi
Agency class:
Industry
Collaborator:
Agency:
Intergroupe Francophone du Myelome
Agency class:
Other
Source:
Poitiers University Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05889221
