Lenalidomide, Bortezomib and Dexamethasone Induction Therapy With Either Intravenous or Subcutaneous Isatuximab in Patients With Newly Diagnosed Multiple Myeloma

Study Purpose

The trial aims to demonstrate the non-inferiority of subcutaneos to intravenous isatuximab administration in transplant-eligible patients with newly diagnosed multple myeloma.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years - 70 Years
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- Confirmed diagnosis of untreated MM requiring systemic therapy (diagnostic criteria according to IMWG) - Patient is eligible for high-dose melphalan (200 mg/m^2 melphalan) and autologous stem cell transplantation.

- 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; involved FLC level ≥ 10 mg/dL provided sFLC ratio is abnormal.

- Age 18-70 years at trial inclusion.

Exclusion Criteria:

- Patient has known hypersensitivity (or contraindication) to any of the components of study therapy.

- Systemic amyloid light-chain amyloidosis (except for localized AL amyloidosis limited to the skin or the bone marrow) - Plasma cell leukemia.

- Previous chemotherapy or radiotherapy during the past 5 years except local radiotherapy in case of local MM progression.

- Severe cardiac dysfunction (NYHA classification III-IV) - Patients with active or uncontrolled hepatitis B or C or detectable liver disease due to hepatitis B or C.

- HIV positivity.

- Patients with active, uncontrolled infections.

- Patients with severe renal insufficiency or requiring hemodialysis.

- Patients with peripheral neuropathy or neuropathic pain, grade 2 or higher (as defined by the NCI Common Terminology Criteria for Adverse Events) - 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.

- Platelet count < 75 x 10^9/L.

- Haemoglobin ≤ 8.0 g/dL, unless related to MM.

- 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) - Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L) - Pregnancy and lactation.

For further details on inclusion/exclusion criteria please refer to the study protocol.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05804032
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	University of Heidelberg Medical Center
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Hartmut Goldschmidt, Prof.
Principal Investigator Affiliation	GMMG study group
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other, Industry
Overall Status	Recruiting
Countries	Austria, Germany
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Multiple Myeloma

Additional Details

Prospective, multicentre, randomised, parallel group, open, phase III clinical trial, for patients with confirmed diagnosis of untreated multiple myeloma requiring systemic therapy. Investigational Medicinal Product: Isatuximab, subcutaneous administration via a wearable injector system. Randomization: Patients are randomized in one of 2 study arms (A or B) before induction therapy. Patients randomized in arm A will receive 3 cycles of the monoclonal antibody isatuximab intravenously, combined with RVd regimen (Lenalidomide, Bortezomib, Dexamethasone). Each cycle will last for 42 days. Patients in arm B will receive 3 cycles RVd plus isatuximab subcutaneously. After induction therapy, patients will receive standard intensification (usually cyclophosphamide-based mobilization therapy, stem cell collection and high-dose melphalan followed by autologous stem cell transplantation (HDM/ASCT)). End of study will be after the first HDM/ASCT. There is one primary objective: 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). Key secondary objectives are: 1. Comparison of patient-reported outcomes (PRO) regarding route of administration of isatuximab (SC vs.#46; 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. The duration of the trial for each patients is expected to be approximately 10 months (induction and intensification treatment).

Arms & Interventions

Arms

Active Comparator: Arm A - Intravenous isatuximab

Patients in arm A are treated with 3 cycles RVd + i.v. isatuximab, followed by a standard intensification and autologous stem cell transplantation.

Experimental: Arm B - Subcutaneous isatuximab

Patients in arm B are treated with 3 cycles RVd + s.c. isatuximab, followed by a standard intensification and autologous stem cell transplantation.

Interventions

Drug: - Isatuximab

IV isatuximab will be administered weekly in the first cycle (Cycle 1) on days 1, 8, 15, 22, 29, and biweekly on the 2 subsequent cycles at days 1, 15 and 29, at the dose of 10 mg/kg.

Drug: - Isatuximab

SC isatuximab will be administered on days 1, 8, 15, 22, 29 of cycle 1, and on days 1, 15 and 29 of cycles 2-3, at the dose of 1400 mg

Drug: - Lenalidomide

Both arms: 25 mg per os on day 1-14 and d22-35 in induction cycle 1-3

Drug: - Bortezomib

Both arms: 1.3 mg/m^2 subcutaneous on day 1, 4, 8, 11, 22, 25, 29 32 in 3 induction cycles

Drug: - Dexamethasone

20 mg per os on day 1-2, 4-5, 8-9, 11-12, 15; and 22-23, 25-26, 29-30, 32-33 in induction cycles 1-3.

Contact a Trial Team

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International Sites

Salzburg, Austria

Status

Recruiting

Address

Universitätsklinikum der Paracelsus, 3. Med. Abteilung/Onkologie Ambulanz

Salzburg, , 5020

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