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

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ClinicalTrials.gov Identifier: NCT05804032
Recruitment Status : Recruiting
First Posted : April 7, 2023
Last Update Posted : January 10, 2024
Sponsor:
Collaborators:
Deutsche Studiengruppe Multiples Myelom (DSMM)
KKS Netzwerk
Sanofi
Information provided by (Responsible Party):
Prof. Dr. Hartmut Goldschmidt, University of Heidelberg Medical Center

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

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Isatuximab Drug: Lenalidomide Drug: Bortezomib Drug: Dexamethasone Phase 3

Detailed Description:

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. 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).

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 514 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase III Non-inferiority Trial Assessing Lenalidomide, Bortezomib and Dexamethasone Induction Therapy With Either Intravenous or Subcutaneous Isatuximab in Transplant-eligible Patients With Newly Diagnosed Multiple Myeloma.
Actual Study Start Date : April 14, 2023
Estimated Primary Completion Date : July 24, 2025
Estimated Study Completion Date : July 24, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arms and Interventions
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Arm Intervention/treatment
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.
 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.
Other Name: Sarclisa

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
Other Name: Velcade

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.
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.
 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
Other Name: Sarclisa

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
Other Name: Velcade

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.


Outcome Measures
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Primary Outcome Measures :
  1. Demonstration of non-inferiority of subcutaneous (SC) isatuximab compared to intravenous (IV) isatuximab, both in combination with RVd. [ Time Frame: 18 weeks after start of study treatment ]
    Rates of VGPR or better (according to standard IMWG response criteria), defined as proportion of patients with at least VGPR after induction therapy (according to standard International Myeloma Working Group (IMWG) response criteria).


Secondary Outcome Measures :
  1. Quality of life compared between Arm A and B. [ Time Frame: 18 weeks after start of study treatment ]
    Comparison of PRO (patient-reported outcome) 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 in Arm B compared to Arm A [ Time Frame: 18 weeks after start of study treatment ]
    Rates of NGS-MRD negativity (sensitivity 10^-5, from bone marrow aspirate) after induction therapy

  3. Rates of MRD negativity by NGS and NGF (sensitivity 10^-5, from BMA) independent of standard IMWG response after first HDM/ASCT [ Time Frame: 18 weeks (timepoint "after induction") or 35 weeks (timepoint "after first HDM/ASCT") after start of study treatment ]
    defined as proportion of negative patients with the corresponding MRD method (NGS or NGF) at the defined timepoint (after induction therapy or first HDM/ASCT)

  4. Rates of best overall response to treatment (BOR) [ Time Frame: Depending on the timepoint of best response out of all response assessments, up to 10 months from randomization ]
    proportion of patients with BOR (at least PR or better) to treatment until end of study (based on timepoints post induction cycle 2 and 3, prior to HDM/ASCT and post first HDM/ASCT)

  5. Progression-free survival (PFS) [ Time Frame: Until EOS (28 months after start of study) ]
    Time from randomization (at study inclusion) to progression or death from any cause whichever occurs first


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05804032


Contacts
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Contact: Hartmut Goldschmidt, Prof. +49 6221 568198 s.gmmg@med.uni-heidelberg.de

Locations
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Sponsors and Collaborators
University of Heidelberg Medical Center
Deutsche Studiengruppe Multiples Myelom (DSMM)
KKS Netzwerk
Sanofi
Investigators
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Principal Investigator: Hartmut Goldschmidt, Prof. GMMG study group
More Information
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Responsible Party: Prof. Dr. Hartmut Goldschmidt, Principal Investigator, University of Heidelberg Medical Center
ClinicalTrials.gov Identifier: NCT05804032    
Other Study ID Numbers: GMMG-HD8/DSMM XIX
First Posted: April 7, 2023    Key Record Dates
Last Update Posted: January 10, 2024
Last Verified: January 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Prof. Dr. Hartmut Goldschmidt, University of Heidelberg Medical Center:
Neoplasms
Paraproteinemias
Lymphoproliferative Disorders
Immunoproliferative Disorders
Lenalidomide
 Bortezomib
Dexamethasone
Isatuximab
Monoclonal antibodies
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
 Lenalidomide
Bortezomib
Antibodies, Monoclonal
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunologic Factors