A randomized phase III non-inferiority trial assessing lenalidomide, bortezomib and dexame-thasone induction therapy with either intravenous or subcutaneous isatuximab in patients with newly diagnosed multiple myeloma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Heidelberg AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15], Diseases [C] - Neoplasms [C04]

Trial duration

7 Mar 2023 → 30 Jan 2026

Decision date (initial)

2024-11-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516300-41-00

EudraCT number

2022-000996-38

ClinicalTrials.gov

NCT06216158

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

Demonstration of non-inferiority of subcutaneous (SC) isatuximab compared to intravenous (IV) isatuximab, both in combination with RVd, with respect to rates of VGPR or better after induction therapy (according to standard International Myeloma Working Group (IMWG) response criteria).

Secondary objectives 2

1. Comparison of PRO regarding route of administration of isatuximab (SC vs. IV) on induction therapy as assessed by modified CTSQ (modified 9-item questionnaire).
2. Non-inferiority of rates of MRD negativity (assessed by NGS from BMA; sensitivity 10-5) independent of standard IMWG response after induction therapy.

Conditions and MedDRA coding

Multiple Myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Confirmed diagnosis of untreated MM requiring systemic therapy (diagnostic criteria according to IMWG)
2. Patient is eligible for HDM (200 mg/m^2 melphalan) and ASCT
3. Measurable MM disease according to IMWG criteria, defined as any quantifiable monoclonal protein value, defined by at least one of the following three measurements: Serum M-protein ≥ 10 g/L; Urine light-chain (M-protein) of ≥ 200 mg/24 hours; Serum FLC assay: involved FLC level ≥ 10 mg/dL provided sFLC ratio is abnormal
4. Age 18-70 years at trial inclusion
5. WHO performance status 0-2
6. Negative pregnancy test at inclusion in women of childbearing potential
7. For all men and women of childbearing potential: patients must be willing and capable to use adequate contraception during the complete therapy
8. All patients must agree to abstain from donating blood while taking lenalidomide and for 28 days following discontinuation of lenalidomide therapy
9. Ability of patient to understand character and individual consequences of the clinical trial
10. Written informed consent (must be available before enrolment in the trial)

Exclusion criteria 21

1. Patient has known hypersensitivity (or contraindication) to dexamethasone, 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 or H1 blockers that would prohibit further treatment with these agents
2. Systemic AL amyloidosis (except for localized AL amyloidosis limited to the skin or the bone marrow)
3. Plasma cell leukemia (as defined by more than 20% circulating plasma cells and/or an absolute count greater than 2 × 10^9/L plasma cells in the peripheral blood smears
4. Previous chemotherapy or radiotherapy during the past 5 years except local radiotherapy in case of local MM progression. (Note: patients may have received a cumulative dose of up to 160 mg of dexamethasone or equivalent as emergency therapy for MM.)
5. Severe cardiac dysfunction (NYHA classification III-IV)
6. Significant hepatic dysfunction (ASAT and/or ALAT ≥ 3 times normal level and/or serum bilirubin ≥ 1.5 times normal level if not due to hereditary abnormalities as Gilbert’s disease), unless related to MM
7. Patients with active or uncontrolled hepatitis B or C or detectable liver disease due to hepatitis B or C.
8. HIV positivity
9. Patients with active, uncontrolled infections
10. Patients with severe renal insufficiency (Creatinine Clearance < 30 mL/min) or requiring hemodialysis
11. Patients with peripheral neuropathy or neuropathic pain, grade 2 or higher (as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE, version 5.0)
12. Patients with a history of any active malignancy during the past 5 years with the exception of following malignancies after curative therapy: basal cell carcinoma of the skin, squamous cell skin carcinoma, stage 0 cervical carcinoma or any in situ malignancy
13. Patients with acute diffuse infiltrative pulmonary and/or pericardial disease
14. Autoimmune hemolytic anemia with positive indirect Coombs test or immune thrombocytopenia
15. Platelet count < 75 x 10^9/L
16. Haemoglobin ≤ 8.0 g/dL, unless related to MM
17. Absolute neutrophil count (ANC) < 1.0 x 10^9/L (the use of colony stimulating factors within 14 days before the test is not allowed)
18. Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L)
19. Unable or unwilling to undergo thromboprophylaxis
20. Pregnancy and lactation
21. Participation in other interventional clinical trials. This does not include long-term follow-up periods without active drug treatment of previous studies during the last 6 months

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Rates of VGPR or better (according to standard IMWG response criteria), defined as proportion of patients with at least VGPR after induction therapy

Secondary endpoints 2

1. PRO outcomes score assessed by CTSQ (subdomain “satisfaction with therapy”) for SC vs. IV isatuximab application on induction therapy
2. Rates of NGS-MRD negativity (sensitivity 10^-5, from BMA) after induction therapy

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Heidelberg AöR

Sponsor organisation

Universitaetsklinikum Heidelberg AöR

Address

Im Neuenheimer Feld 672, Neuenheim Neuenheim

City

Heidelberg

Postcode

69120

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Heidelberg AöR

Contact name

GMMG Studiensekretariat

Public contact point

Organisation

Universitaetsklinikum Heidelberg AöR

Contact name

GMMG Studiensekretariat

Locations

2 EU/EEA countries · 81 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 23 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications