| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10028228 |
| E.1.2 | Term | Multiple myeloma |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To demonstrate the benefit of Isatuximab (ISA) in combination with CellProtect in the enhancement of overall response rate (ORR) as compared to Isatuximab in patients with newly diagnosed multiple myeloma (NDMM) eligible for transplant as maintenance treatment after high dose treatment (HDT). |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate the time to progression (TTP).
To evaluate PFS.
To evaluate the duration of response (DOR).
To evaluate the overall survival (OS).
To evaluate safety.
Exploratory objectives:
To evaluate comparative serum cytokine and chemokine profiling in both arms
To evaluate comparative detailed phenotypic analyses of BMMC and PBMCs in both arms
To evaluate the CD38 expression of circulating activated NK cells |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Active multiple myeloma, as defined by the IMWG criteria.
2. Evidence of measurable disease:
3. Serum monoclonal (M)-protein ≥1.0 g/dL measured using serum protein immunoelectrophoresis
a. and/or
4. Urine M-protein ≥200 mg/24 hours measured using urine protein immunoelectrophoresis
a. and/or
5. in patients without measurable M protein in serum or urine as per previous criteria, serum immunoglobulin free light chain (sFLC) ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio <0.26 or >1.65.
6. Patients who are newly diagnosed and considered for high-dose chemotherapy
7. Patient has given voluntary written informed consent before performance of any study related procedures not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to his/her medical care.
8. ≥18 years of age (and satisfying the legal age of consent in the jurisdiction in which the study is taking place)
9. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
10. Male or Female
a) Male participants
A male participant must agree to use contraception of this protocol during the intervention period and for at least 5 months after the last dose of study treatment and refrain from donating sperm during this period.
b) Female participants
A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
Not a Females of childbearing potential (FCBP),
OR
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 of starting study medication and must either commit to continue abstinence from heterosexual intercourse or apply a highly effective method of birth control until at least 5 months after last dose of study treatment
|
|
| E.4 | Principal exclusion criteria |
1. Prior or concurrent exposure to NK cells and NK like T cells, or Approved or investigational treatments for MM.
2. Diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma (asymptomatic multiple myeloma with absence of related organ or tissue impairment end organ damage).
3. 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.
4. Prior or current systemic therapy, or SCT for symptomatic multiple myeloma, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for 4 days) of corticosteroids, if completed within 14 days prior to randomization.
5. Concomitant plasma cell leukemia.
6. Any major procedure within 14 days before the initiation of the study treatment: plasmapheresis, major surgery (kyphoplasty is not considered a major procedure), radiotherapy (except if palliative intent).
7. ECOG PS >2.
8. Hemoglobin <8 g/dL.
9. Platelets <70 × 10*9/L if <50% of bone marrow (BM) nucleated cells are plasma cells, and ≤30 × 10*9/L if ≥50% of BM nucleated cells are plasma cells. Platelet transfusion is not allowed within 3 days before the screening haematological test.
10. Total bilirubin >1.5 × upper limit of normal (ULN), except for known Gilbert syndrome.
11. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3 × ULN.
12. Hypersensitivity (or contraindication) to steroids, sucrose histidine (as base and hydrochloride salt), boron, mannitol, and polysorbate 80 or any of the components of study therapy that are not amenable to premedication with steroids, pregelatinized starch, sodium stearyl fumarate, arginine hydrochloride, poloxamer 188, sucrose or any of the other components of study therapy
13. Any of the following within 6 months prior to randomization:
14. Second/third degree heart block
15. Poorly controlled hypertension
16. Myocardial infarction
17. Severe/unstable angina pectoris
18. Coronary/peripheral artery bypass graft
19. New York Heart Association class III or IV congestive heart failure
20. Grade ≥3 arrhythmias
21. Stroke or transient ischemic attack.
22. Left-ventricular ejection fraction <40%.
23. Prior malignancy. Adequately treated basal cell or squamous cell skin, or superficial (pTis, pTa, and pT1) bladder cancer, or low risk prostate cancer, or any in situ malignancy after curative therapy are allowed, as well as any other cancer for which cytotoxic chemotherapy has been completed ≥3 years prior to enrolment and from which the patient has been disease-free for ≥3 years.
24. Known acquired immunodeficiency syndrome (AIDS)-related illness or known HIV disease requiring antiviral treatment or active hepatitis A (defined as positive HA antigen), B (defined as either positive HBs antigen or negative HBs antigen with positive HBc antibody), or C infection (defined as a known positive hepatitis C antibody result and known quantitative hepatitis C (HCV) ribonucleic acid (RNA) results greater than the lower limits of detection of the assay). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
To evaluate in both randomized (ISA and ISA/CellProtect) arms the occurrence after maintenance start of:
Very good partial response (VGPR) or better rate, as defined by the International Myeloma Working Group (IMWG) criteria.
Co-primary objective will be assessment of minimal residual disease (MRD) negativity rate in patients with CR or VGPR and conversion from MRD positive to MRD negative checked after first cycle of Isatuximab and before start of monthly Isatuximab. The aforementioned assessment will also be conducted at 12 and 24 months after start maintenance.
Complete response (CR) rate, as defined by the IMWG criteria. MRD negativity rate for both CR and VGPR patients, defined as the proportion of patients for whom MRD is negative. Bone marrow aspirates will be collected. Threshold for negativity will be at least 10-5.
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Continously from start of study treatment until end of study |
|
| E.5.2 | Secondary end point(s) |
• Progression-free survival on/after study medication, defined as the time from the date of the start of maintenance treatment to the date of
documented progressive disease (PD) or death, whichever comes first.
• Time from the date of randomization to the date of initial documented progression according to the International Myeloma Working Group (IMWG) diagnostic criteria for MM requiring systemic therapy or to the date of death, whichever occurs first.
• TTP, defined as the time from randomization to the date of first documentation of PD (as determined by the IRC using the IMWG criteria).
• DOR, defined as the time from the date of the first IRC determined response to the date of first IRC PD or death, whichever occurs first. Duration
of response will determined only for patients who have achieved CR, VGPR, or PR.
• PFS (defined as the time from the date of randomization to the date of first documentation of PD or the date of death from any cause, whichever
comes first by MRD status.
• OS, defined as the time from the date of randomization to death from any cause.
Safety in terms of treatment-emergent adverse events/serious adverse events (TEAEs/SAEs) (including IARs), laboratory parameters, vital signs, weight, ECOG PS, and findings from physical examination. TEAEs are defined as AEs that develop, worsen (according to the Investigator opinion),
or become serious during the treatment period. The treatment period is defined as the time from first dose of study treatments up to 30 days after last dose of study treatments or initiation of further anti-myeloma therapy, whichever occurs first.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Continously until end of study |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
Print
