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

Primary Purpose

Multiple Myeloma

Status
Recruiting
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
Isatuximab
Isatuximab
Lenalidomide
Bortezomib
Dexamethasone
Sponsored by
University of Heidelberg Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Neoplasms, Paraproteinemias, Lymphoproliferative Disorders, Immunoproliferative Disorders, Lenalidomide, Bortezomib, Dexamethasone, Isatuximab, Monoclonal antibodies

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Uniklinik RWTH Aachen, Klinik für Hämatologie, Onkologie, Hämostaseologie und StammzelltransplantationRecruiting
  • Klinikum Augsburg, II. Medizinische Klinik Hämatologie/Onkologie
  • Helios Klinikum Bad Saarow, Klinik für Hämatologie, Onkologie und Palliativmedizin
  • Charité, III. Medizinische Abteilung (Hämatologie/Onkologie)
  • Vivantes Klinikum Neukölln, Klinik für Hämatologie und Onkologie
  • Universitätsklinikum Bonn, Medizinische Klinik III
  • Klinikum Chemnitz gGmbH
  • Carl-Thiem-Klinikum Cottbus gGmbH, 2. Medizinische KlinikRecruiting
  • Klinikum Darmstadt, Medizinische Klinik V Hämatologie/Onkologie
  • Universitätsklinikum Carl Gustav Carus an der TU Dresden, Medizinische Klinik und Poliklinik I
  • Helios St. Johannes Klinik Duisburg, Medizinische Klinik 2
  • Universitätsklinikum Düsseldorf, Klinik für Hämatologie, Onkologie und Klinische Immunologie
  • Marien Hospital Düsseldorf GmbH, Klinik für Onkologie, Hämatalogie und PalliativmedizinRecruiting
  • St. Antonius-Hospital Eschweiler, Klinik für Hämatologie / OnkologieRecruiting
  • KEM I Evang. Kliniken Essen-Mitte gGmbH, Evangelisches Krankenhaus Essen-Werden gGmbH, Klinik für Hämatologie, Onkologie und Stammzelltransplantation
  • Universitätsklinikum Frankfurt, Medizinische Klinik 2, Hämatologie/Onkologie
  • Universitätsklinikum Hamburg-Eppendorf, Zentrum für Onkologie
  • Onkologische Schwerpunktpraxis Heidelberg
  • Universitätsklinikum Heidelberg, Medizinische Klinik VRecruiting
  • SLK Kliniken Heilbronn, Medizinische Klinik IIIRecruiting
  • Universitätsklinikum des Saarlandes, Klinik für Innere Medizin 1
  • Klinikum der Friedrich-Schiller-Universität Jena, Klinik für Innere Medizin II, Abteilung Hämatologie und internistische OnkologieRecruiting
  • Mannheimer Onkologie Praxis
  • Kliniken Maria Hilf GmbH, Medizinische Klinik IRecruiting
  • Krankenhaus Barmherzige Brüder Regensburg, Klinik für Onkologie und Hämatologie
  • Diakonie-Klinikum Schwäbisch Hall gGmbH, Innere Medizin III (Tumorerkrankungen, Palliativmedizin)Recruiting
  • ZAHO-Zentrum für ambulante Hämatologie und Onkologie
  • Onkologische Schwerpunktpraxis SpeyerRecruiting
  • Universität Tübingen, Medizinische Universitätsklinik, Innere Medizin II: Onkologie, Hämatologie, Klinische Immunologie und RheumatologieRecruiting
  • University of Würzburg, Med. Klinik und Poliklinik IIRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm A - Intravenous isatuximab

Arm B - Subcutaneous isatuximab

Arm Description

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

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

Outcomes

Primary Outcome Measures

Demonstration of non-inferiority of subcutaneous (SC) isatuximab compared to intravenous (IV) isatuximab, both in combination with RVd.
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

Quality of life compared between Arm A and B.
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)
Non-inferiority of rates of MRD negativity in Arm B compared to Arm A
Rates of NGS-MRD negativity (sensitivity 10^-5, from bone marrow aspirate) after induction therapy
Rates of MRD negativity by NGS and NGF (sensitivity 10^-5, from BMA) independent of standard IMWG response after first HDM/ASCT
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)
Rates of best overall response to treatment (BOR)
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)
Progression-free survival (PFS)
Time from randomization (at study inclusion) to progression or death from any cause whichever occurs first

Full Information

First Posted
March 21, 2023
Last Updated
June 26, 2023
Sponsor
University of Heidelberg Medical Center
Collaborators
Deutsche Studiengruppe Multiples Myelom (DSMM), KKS Netzwerk, Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT05804032
Brief Title
Lenalidomide, Bortezomib and Dexamethasone Induction Therapy With Either Intravenous or Subcutaneous Isatuximab in Patients With Newly Diagnosed Multiple Myeloma
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.
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 14, 2023 (Actual)
Primary Completion Date
July 24, 2025 (Anticipated)
Study Completion Date
July 24, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Heidelberg Medical Center
Collaborators
Deutsche Studiengruppe Multiples Myelom (DSMM), KKS Netzwerk, Sanofi

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.
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: 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). 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Neoplasms, Paraproteinemias, Lymphoproliferative Disorders, Immunoproliferative Disorders, Lenalidomide, Bortezomib, Dexamethasone, Isatuximab, Monoclonal antibodies

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
514 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A - Intravenous isatuximab
Arm Type
Active Comparator
Arm Description
Patients in arm A are treated with 3 cycles RVd + i.v. isatuximab, followed by a standard intensification and autologous stem cell transplantation.
Arm Title
Arm B - Subcutaneous isatuximab
Arm Type
Experimental
Arm Description
Patients in arm B are treated with 3 cycles RVd + s.c. isatuximab, followed by a standard intensification and autologous stem cell transplantation.
Intervention Type
Drug
Intervention Name(s)
Isatuximab
Other Intervention Name(s)
Sarclisa
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Isatuximab
Other Intervention Name(s)
Sarclisa
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Intervention Description
Both arms: 25 mg per os on day 1-14 and d22-35 in induction cycle 1-3
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Other Intervention Name(s)
Velcade
Intervention Description
Both arms: 1.3 mg/m^2 subcutaneous on day 1, 4, 8, 11, 22, 25, 29 32 in 3 induction cycles
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
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.
Primary Outcome Measure Information:
Title
Demonstration of non-inferiority of subcutaneous (SC) isatuximab compared to intravenous (IV) isatuximab, both in combination with RVd.
Description
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).
Time Frame
18 weeks after start of study treatment
Secondary Outcome Measure Information:
Title
Quality of life compared between Arm A and B.
Description
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)
Time Frame
18 weeks after start of study treatment
Title
Non-inferiority of rates of MRD negativity in Arm B compared to Arm A
Description
Rates of NGS-MRD negativity (sensitivity 10^-5, from bone marrow aspirate) after induction therapy
Time Frame
18 weeks after start of study treatment
Title
Rates of MRD negativity by NGS and NGF (sensitivity 10^-5, from BMA) independent of standard IMWG response after first HDM/ASCT
Description
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)
Time Frame
18 weeks (timepoint "after induction") or 35 weeks (timepoint "after first HDM/ASCT") after start of study treatment
Title
Rates of best overall response to treatment (BOR)
Description
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)
Time Frame
Depending on the timepoint of best response out of all response assessments, up to 10 months from randomization
Title
Progression-free survival (PFS)
Description
Time from randomization (at study inclusion) to progression or death from any cause whichever occurs first
Time Frame
Until EOS (28 months after start of study)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hartmut Goldschmidt, Prof.
Phone
+49 6221 568198
Email
s.gmmg@med.uni-heidelberg.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hartmut Goldschmidt, Prof.
Organizational Affiliation
GMMG study group
Official's Role
Principal Investigator
Facility Information:
Facility Name
Uniklinik RWTH Aachen, Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation
City
Aachen
ZIP/Postal Code
52074
Country
Germany
Individual Site Status
Recruiting
Facility Name
Klinikum Augsburg, II. Medizinische Klinik Hämatologie/Onkologie
City
Augsburg
ZIP/Postal Code
86156
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
Helios Klinikum Bad Saarow, Klinik für Hämatologie, Onkologie und Palliativmedizin
City
Bad Saarow
ZIP/Postal Code
15526
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
Charité, III. Medizinische Abteilung (Hämatologie/Onkologie)
City
Berlin
ZIP/Postal Code
12200
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
Vivantes Klinikum Neukölln, Klinik für Hämatologie und Onkologie
City
Berlin
ZIP/Postal Code
12351
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
Universitätsklinikum Bonn, Medizinische Klinik III
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
Klinikum Chemnitz gGmbH
City
Chemnitz
ZIP/Postal Code
09116
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
Carl-Thiem-Klinikum Cottbus gGmbH, 2. Medizinische Klinik
City
Cottbus
ZIP/Postal Code
03048
Country
Germany
Individual Site Status
Recruiting
Facility Name
Klinikum Darmstadt, Medizinische Klinik V Hämatologie/Onkologie
City
Darmstadt
ZIP/Postal Code
64283
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
Universitätsklinikum Carl Gustav Carus an der TU Dresden, Medizinische Klinik und Poliklinik I
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
Helios St. Johannes Klinik Duisburg, Medizinische Klinik 2
City
Duisburg
ZIP/Postal Code
47166
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
Universitätsklinikum Düsseldorf, Klinik für Hämatologie, Onkologie und Klinische Immunologie
City
Düsseldorf
ZIP/Postal Code
40225
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
Marien Hospital Düsseldorf GmbH, Klinik für Onkologie, Hämatalogie und Palliativmedizin
City
Düsseldorf
ZIP/Postal Code
40479
Country
Germany
Individual Site Status
Recruiting
Facility Name
St. Antonius-Hospital Eschweiler, Klinik für Hämatologie / Onkologie
City
Eschweiler
ZIP/Postal Code
52249
Country
Germany
Individual Site Status
Recruiting
Facility Name
KEM I Evang. Kliniken Essen-Mitte gGmbH, Evangelisches Krankenhaus Essen-Werden gGmbH, Klinik für Hämatologie, Onkologie und Stammzelltransplantation
City
Essen
ZIP/Postal Code
45239
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
Universitätsklinikum Frankfurt, Medizinische Klinik 2, Hämatologie/Onkologie
City
Frankfurt am Main
ZIP/Postal Code
60590
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
Universitätsklinikum Hamburg-Eppendorf, Zentrum für Onkologie
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
Onkologische Schwerpunktpraxis Heidelberg
City
Heidelberg
ZIP/Postal Code
69115
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
Universitätsklinikum Heidelberg, Medizinische Klinik V
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Individual Site Status
Recruiting
Facility Name
SLK Kliniken Heilbronn, Medizinische Klinik III
City
Heilbronn
ZIP/Postal Code
74078
Country
Germany
Individual Site Status
Recruiting
Facility Name
Universitätsklinikum des Saarlandes, Klinik für Innere Medizin 1
City
Homburg
ZIP/Postal Code
66421
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
Klinikum der Friedrich-Schiller-Universität Jena, Klinik für Innere Medizin II, Abteilung Hämatologie und internistische Onkologie
City
Jena
ZIP/Postal Code
07740
Country
Germany
Individual Site Status
Recruiting
Facility Name
Mannheimer Onkologie Praxis
City
Mannheim
ZIP/Postal Code
68161
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
Kliniken Maria Hilf GmbH, Medizinische Klinik I
City
Mönchengladbach
ZIP/Postal Code
41063
Country
Germany
Individual Site Status
Recruiting
Facility Name
Krankenhaus Barmherzige Brüder Regensburg, Klinik für Onkologie und Hämatologie
City
Regensburg
ZIP/Postal Code
93049
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
Diakonie-Klinikum Schwäbisch Hall gGmbH, Innere Medizin III (Tumorerkrankungen, Palliativmedizin)
City
Schwäbisch Hall
ZIP/Postal Code
74523
Country
Germany
Individual Site Status
Recruiting
Facility Name
ZAHO-Zentrum für ambulante Hämatologie und Onkologie
City
Siegburg
ZIP/Postal Code
53721
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
Onkologische Schwerpunktpraxis Speyer
City
Speyer
ZIP/Postal Code
67346
Country
Germany
Individual Site Status
Recruiting
Facility Name
Universität Tübingen, Medizinische Universitätsklinik, Innere Medizin II: Onkologie, Hämatologie, Klinische Immunologie und Rheumatologie
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Individual Site Status
Recruiting
Facility Name
University of Würzburg, Med. Klinik und Poliklinik II
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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