Trial on the Effect of Isatuximab to Lenalidomide/Bortezomib/Dexamethasone (RVd) Induction and Lenalidomide Maintenance in Patients With Newly Diagnosed Myeloma (GMMG HD7)

NCT03617731 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: GMMG HD7
• Study Type: interventional
• Target: 662
• Locations: 1 country
• Sites: 72

Brief Summary

Trial in patients with newly diagnosed myeloma to evaluate the effect of isatuximab in induction therapy with lenalidomide/bortezomib/dexamethasone (RVd) and in lenalidomide maintenance treatment

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• MRD negativity after induction Treatment (comparison of arms IA and IB)

  Detection of minimal residual disease by flow cytometry (sensitivity at least 1e-5)

  18 weeks after start of study treatment

• Progression Free Survival (PFS) after second randomization (arms IIA and IIB)

  Response Evaluation by IMWG criteria

  time from 2. randomization to progression or death from any cause whichever comes first, censored after three years of maintenance therapy

Secondary Outcomes (14)

• to compare the four treatment arms (IA-IIA, IA-IIB, IB-IIA, IB-IIB) regarding Progression free survival (PFS)

  time from 1. randomization (study inclusion) to progression or death whichever comes first (assessed up to 79 months)

• to compare all 4 treatment arms (IA-IIA, IA-IIB, IB-IIA, IB-IIB) regarding overall survival (OS) from time of 1.randomization

  time from randomisation to time of death from any cause (assessed up to 79 months)

• Overall survival from second randomization

  time from 2. randomization to time of death from any cause (assessed up to 75 months)

• Complete Response (CR) rates after induction therapy

  After induction treatment (18 weeks after start of treatment)

• Complete Response (CR) after high dose therapy

  After high dose therapy (9 or 12 months after start of therapy)

Study Arms (4)

IA

ACTIVE COMPARATOR

Patients in arm IA are treated with 3 cycles RVd (lenalidomide 25 mg/d p.o. d1 - 14 and d22 - 35; bortezomib 1.3 mg/m2 s.c. d1, 4, 8, 11, 22, 25, 29, 32; dexamethasone p.o. 20 mg/d d1-2, 4-5, 8-9, 11-12, 15, 22-23, 25-26, 29-30, 32-33).Treatment repeats every 42 days (d43 = cycle 2 d1). Standard intensification: For all patients, stem cells are mobilized by GMMG Standard protocols (CAD: cyclophosphamide, doxorubicin, dexamethasone) and G-CSF. At least 7.5x106 CD34+ cells/kg body weight are harvested. High dose treatment (melphalan 200mg/m², HDT) followed by autologous stem cell transplantation (ASCT) is started 4 - 6 weeks after CAD. For patients not in CR after HDT1, a second HDT is performed within 3 months.

Drug: Lenalidomide; Drug: Bortezomib; Drug: Dexamethasone

IB

EXPERIMENTAL

Patients in arm IB are treated with 3 cycles RVd + Isatuximab (lenalidomide 25 mg/d p.o. d1 - 14 and d22 - 35; bortezomib 1.3 mg/m2 s.c. d1, 4, 8, 11, 22, 25, 29, 32;dexamethasone p.o. 20 mg/d d1-2, 4-5, 8-9, 11-12, 15, 22-23, 25-26, 29-30, 32-33).Isatuximab (10 mg/kg i.v. C1: d 1, 8, 15, 22, 29; C2-3: d 1, 15, 29).Treatment repeats every 42 days (d43 = cycle 2 d1). Standard intensification: For all patients, stem cells are mobilized by GMMG Standard protocols (CAD: cyclophosphamide, doxorubicin, dexamethasone) and G-CSF. At least 7.5x106 CD34+ cells/kg body weight are harvested. High dose treatment (melphalan 200mg/m², HDT) followed by autologous stem cell transplantation (ASCT) is started 4 - 6 weeks after CAD. For patients not in CR after HDT1, a second HDT is performed within 3 months.

Drug: Lenalidomide; Drug: Bortezomib; Drug: Dexamethasone; Drug: Isatuximab

IIA

ACTIVE COMPARATOR

maintenance treatment with Lenalidomide 10mg/d (increased to 15mg/d after 3 months) repeated every 28d. Maintenance treatment is planned for up to 36 months or until progression if progression occurs first.

Drug: Lenalidomide

IIB

EXPERIMENTAL

maintenance treatment with Lenalidomide 10mg/d (increased to 15mg/d after 3 months) + Isatuximab (10 mg/kg; C1: d1, 8, 15, 22; C2-C3: d1 + 15; C4-39:d1, repeated every 28d). Within the trial, maintenance treatment is planned for up to 36 months or until progression if progression occurs first.

Drug: Lenalidomide; Drug: Isatuximab

Interventions

Bortezomib DRUG

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

Also known as: Velcade

IA; IB

Isatuximab DRUG

10 mg/kg in the vein( i.v) on day 1,8,15, 22, 29 in induction cycle 1 on day 1, 15 and 29 in induction cycle 2 and 3 (Arm IB). 10 mg/kg i.v. on day 1,8, 15 and 22 in maintenance cycle 1, 10 mg/kg i.v. on day 1 and 15 in maintenance cycle 2 and 3, 10 mg/kg i.v. on day 1 in maintenance cycle 4 - 39 (Arm IIB)

IB; IIB

Lenalidomide DRUG

25 mg per os on day 1-14 and d22-35 in induction cycle 1-3 (Arms IA and IB) 10 mg p.o. on day 1-28 in maintenance cycle 1-3, 15 mg p.o. on day 1-28 in maintenance cycle 4-39 (Arms IIA and IIB)

Also known as: Revlimid

IA; IB; IIA; IIB

Dexamethasone DRUG

20 mg per os on day 1,2 and 4,5 and 8,9 and 11,12 and 15 and 22,23 and 25,26 and 29,30 and 32,33 in induction cycles 1-3 (Arms IA and IB). Maintenance cycle 1 on day 1, 8, 15, 22 Dexamethasone 20 mg/d per os (Arm IIA). In Arm IIB Dexamethasone 20 mg i.v. on days of Isatuximab infusion in the first maintenance cycle (d 1, 8, 15, 22), dexamethasone will be administered intravenously as part of the premedication. If an isatuximab dose is skipped or discontinued dexamethasone should be administered orally.

IA; IB

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is eligible for high dose therapy and autologous stem cell transplantation.
• Measurable disease, defined as any quantifiable monoclonal protein value, defined by at least one of the following three measurements:2
• Serum M-protein ≥ 10g/l (for IgA ≥ 5g/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
• Age 18 - 70 years inclusive
• WHO performance status 0-2
• All patients must agree on the requirements regarding the lenalidomide pregnancy prevention plan described in section 6. For all men and females of childbearing potential: patients must be willing and capable to use adequate contraception during the complete therapy.
• All patients must
• agree to abstain from donating blood while taking lenalidomide and for 28 days following discontinuation of lenalidomide therapy
• agree not to share study drug lenalidomide with another person and to return all unused study drug to the investigator or pharmacist
• Ability of patient to understand character and individual consequences of the clinical trial
• Provide written informed consent (must be available before enrolment in the trial)

You may not qualify if:

• 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 H2 blockers that would prohibit further treatment with these agents.
• Systemic AL amyloidosis (except for AL amyloidosis of the skin or the bone marrow)
• Plasma cell leukemia
• Severe cardiac dysfunction (NYHA classification III-IV), ejection fraction \< 40%
• 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 myeloma.
• Patients with active or history of hepatitis B or C
• HIV positivity
• Patients with active, uncontrolled infections
• Patients with severe renal insufficiency (Creatinine Clearance \< 30ml/min)
• Patients with peripheral neuropathy or neuropathic pain, CTC grade 2 or higher (as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0)
• Patients with a history of 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
• Patients with acute diffuse infiltrative pulmonary and/or pericardial disease
• Autoimmune hemolytic anemia with positive Coombs test or immune thrombocytopenia
• Platelet count \< 75 x 109/l
• Haemoglobin \< 8.0 g/dl, unless related to myeloma

Sponsors & Collaborators

• University of Heidelberg Medical Center: lead

Study Sites (72)

Uniklinik RWTH Aachen, Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation

Aachen, 52074, Germany

Location

Helios Klinikum Bad Saarow, Klinik für Hämatologie, Onkologie und Palliativmedizin

Bad Saarow, 15526, Germany

Location

Charité, Campus Benjamin Franklin , III. Medizinische Abteilung (Hämatologie/Onkologie)

Berlin, 12200, Germany

Location

Vivantes Klinikum Neukölln, Klinik für Hämatologie und Onkologie

Berlin, 12351, Germany

Location

HELIOS Klinikum, Klinik für Hämatologie, Onkologie und Immunologie

Berlin, 13125, Germany

Location

Studiengesellschaft Onkologie Bielefeld GbR

Bielefeld, 33604, Germany

Location

Klinikum Bielefeld, Klinik für Hämatologie, Onkologie und Palliativmedizin

Bielefeld, D-33604, Germany

Location

Medizinische Universitätsklinik, Knappschaftskrankenhaus

Bochum, D-44892, Germany

Location

Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik III, Schwerpunkt Onkologie, Hämatologie und Rheumatologie

Bonn, 53105, Germany

Location

Johanniter Krankenhaus Bonn

Bonn, 53113, Germany

Location

Zentrum für ambulante Hämatologie und Onkologie (ZAHO)

Bonn, 53113, Germany

Location

Städtisches Klinikum Braunschweig, Med. Klinik III, Hämatologie und Onkologie

Braunschweig, 38114, Germany

Location

Klinikum Chemnitz GmbH, Innere Medizin III

Chemnitz, D-09116, Germany

Location

Uniklinik Köln, Klinik I für Innere Medizin

Cologne, 50937, Germany

Location

Carl-Thiem-Klinikum Cottbus gGmbH, II. Medizinische Klinik

Cottbus, 03048, Germany

Location

Onkologisches Studienzentrum Darmstadt

Darmstadt, 64283, Germany

Location

Klinikum Darmstadt, Med. Klinik V, Hämatologie/Onkologie

Darmstadt, D-64283, Germany

Location

Universitätsklinikum Carl Gustav Carus Dresden, an der Technischen Universität Dresden, Medizinische Klinik und Poliklinik I

Dresden, 01307, Germany

Location

HELIOS St. Johannes Klinik, Akademisches Krankenhaus der Heinrich-Heine-Universität Düsseldorf

Duisburg, 47166, Germany

Location

Marien Hospital Düsseldorf GmbH, Klinik für Onkologie, Hämatologie und Palliativmedizin

Düsseldorf, 40479, Germany

Location

Universitätsklinikum Düsseldorf, Klinik für Hämatologie,Onkologie und Klin. Immunologie

Düsseldorf, D-40225, Germany

Location

Universitätsklinik Erlangen

Erlangen, 91054, Germany

Location

St. Antonius-Hospital Eschweiler, Klinik für Hämatologie / Onkologie

Eschweiler, 52249, Germany

Location

Universitätsklinikum Essen, Klinik für Hämatologie

Essen, D-45147, Germany

Location

Ev. Krankenhaus Essen-Werden gGmbH, Zentrum für Innere Medizin, Klinik für Hämatologie, Onkologie und Stammzelltransplantation

Essen, D-45239, Germany

Location

Gemeinschaftspraxis Prof. Dr. Michael Kiehl und Dipl. Med. Wolfgang Stein

Frankfurt (Oder), 15236, Germany

Location

Klinikum Frankfurt (Oder) GmbH

Frankfurt (Oder), 15236, Germany

Location

Centrum für Hämatologie und Onkologie Bethanien

Frankfurt am Main, 60389, Germany

Location

Agaplesion Markus Krankenhaus, Med. Klinik I

Frankfurt am Main, 60431, Germany

Location

Krankenhaus Nordwest, Institut für Klinisch-Onkologische Forschung

Frankfurt am Main, 60488, Germany

Location

Universitätsklinikum Frankfurt, Goethe-Universität Medizinische Klinik II

Frankfurt am Main, 60590, Germany

Location

Klinikum Fulda, Klinisches Studienzentrum GmbH

Fulda, 36043, Germany

Location

Universitätsklinik der Justus-Liebig-Universität, Medizinische Klinik IV

Giessen, 35385, Germany

Location

Katholisches Karl-Leisner-Klinikum gGmbH, Wilhelm-Anton-Hospital Goch, Klinik für Hämatologie - Onkologie

Goch, 47574, Germany

Location

Kath. Krankenhaus Hagen gGmbH, Abt. Hämatologie/Onkologie

Hagen, D-58095, Germany

Location

Asklepios Klinik Hamburg St. Georg

Hamburg, 20099, Germany

Location

Universitätsklinikum Hamburg Eppendorf, Zentrum für Onkologie, Studienzentrale der II. Medizinischen Klinik

Hamburg, 20246, Germany

Location

Asklepios Klinik Hamburg Altona, II. Med. Klinik

Hamburg, D-22763, Germany

Location

Immunologisch-onkologisches MVZ am Siloah Krankenhaus

Hanover, 30449, Germany

Location

KRH Klinikum Siloah, Klinik für Hämatologie und Onkologie

Hanover, 30459, Germany

Location

Onkologische Schwerpunktpraxis Heidelberg

Heidelberg, 69115, Germany

Location

Krankenhaus St. Vincentius der evangelischen Stadtmission Heidelberg, Abt. Hämatologie, Onkologie, Rheumatologie

Heidelberg, 69117, Germany

Location

University Hospital Heidelberg, Med. Klinik V

Heidelberg, D-69120, Germany

Location

SLK Kliniken Heilbronn, Med. Klinik III

Heilbronn, D-74078, Germany

Location

Marien Hospital Herne

Herne, 44625, Germany

Location

Universitätsklinikum des Saarlandes, Innere Medizin I

Homburg (Saar), 66421, Germany

Location

Westpfalz-Klinikum GmbH, Klinik für Innere Medizin I

Kaiserslautern, 67655, Germany

Location

Städtisches Klinikum Karlsruhe

Karlsruhe, 76133, Germany

Location

Praxisklinik für Hämatologie und Onkologie

Koblenz, D-56068, Germany

Location

Gemeinschaftspraxis für Hämatologie und Onkologie am Caritas Krankenhaus

Lebach, 66822, Germany

Location

Universitätsklinikum Leipzig AöR, Medizinische Klinik und Poliklinik I-Hämatologie und Zelltherapie, Internistische Onkologie, Hämostaseologie

Leipzig, 04103, Germany

Location

Med. Klinik A, Klinikum der Stadt Ludwigshafen am Rhein gGmbH

Ludwigshafen am Rhein, 67063, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, III. Med. Klinik

Mainz, D-55131, Germany

Location

III. Medizinische Klinik Hämatologie und Internistische Onkologie

Mannheim, 68167, Germany

Location

Mannheimer Onkologie Praxis

Mannheim, D-68161, Germany

Location

Philipps-Universität Marburg, Hämatologie/Onkologie/Immunologie

Marburg, 35032, Germany

Location

Mühlenkreiskliniken (AöR) Johannes Wesling Klinikum Minden, Hämatologie/Onkologie, Hämostaseologie und Palliativmedizin

Minden, 32429, Germany

Location

Krankenhaus Maria Hilf GmbH, Franziskuskrankenhaus, Med. Klinik I

Mönchengladbach, D-41063, Germany

Location

Universitätsklinikum Münster, Med. Klinik A

Münster, 48149, Germany

Location

Klinikum Osnabrück GmbH

Osnabrück, 49076, Germany

Location

Brüderkrankenhaus St. Josef Paderborn, Klinik für Hämatologie und Onkologie

Paderborn, 33098, Germany

Location

Krankenhaus Barmherzige Brüder, Klinik für Onkologie und Hämatologie

Regensburg, 93049, Germany

Location

Gemeinschaftspraxis für Hämatologie und Onkologie, Onkologisches Zentrum

Saarlouis, 66740, Germany

Location

Diakonie-Klinikum Schwäbisch Hall gGmbH, Innere Medizin III

Schwäbisch Hall, 74523, Germany

Location

ZAHO-Zentrum für ambulante Hämatologie und Onkologie, Standort Siegburg

Siegburg, D-53721, Germany

Location

Onkologische Schwerpunktpraxis Speyer

Speyer, D-67346, Germany

Location

Klinikum Stuttgart, Stuttgart Cancer Center, Tumorzentrum Eva Mayr-Stihl

Stuttgart, 70174, Germany

Location

Klinikum Mutterhaus der Borromäerinnen gGmbH

Trier, 54290, Germany

Location

University Hospital Tübingen, Med. Klinik und Poliklinik, Abt. II

Tübingen, D-72076, Germany

Location

Bundeswehrkrankenhaus Ulm, Abteilung Innere Medizin - Hämatologie und internistische Onkologie

Ulm, 89081, Germany

Location

Schwarzwald-Baar Klinikum, Innere Medizin II

Villingen-Schwenningen, 78052, Germany

Location

Rems-Murr-Kliniken gGmbH

Winnenden, 71364, Germany

Location

Related Publications (4)

• Mai EK, Bertsch U, Pozek E, Fenk R, Besemer B, Hanoun C, Schroers R, von Metzler I, Hanel M, Mann C, Leypoldt LB, Heilmeier B, Huhn S, Vogel SK, Hundemer M, Scheid C, Blau IW, Luntz S, Weinhold N, Tichy D, Holderried TAW, Trautmann-Grill K, Gezer D, Klaiber-Hakimi M, Muller M, Shumilov E, Knauf W, Michel CS, Geer T, Riesenberg H, Lutz C, Raab MS, Benner A, Hoffmann M, Weisel KC, Salwender HJ, Goldschmidt H; German-Speaking Myeloma Multicenter Group (GMMG) HD7 Investigators; German-speaking Myeloma Multicenter Group (GMMG) HD7. Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone Induction Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma: Final Part 1 Analysis of the GMMG-HD7 Trial. J Clin Oncol. 2025 Apr 10;43(11):1279-1288. doi: 10.1200/JCO-24-02266. Epub 2024 Dec 9.

  PMID: 39652594 DERIVED

• Mai EK, Hielscher T, Bertsch U, Salwender HJ, Zweegman S, Raab MS, Munder M, Pantani L, Mancuso K, Brossart P, Beksac M, Blau IW, Durig J, Besemer B, Fenk R, Reimer P, van der Holt B, Hanel M, von Metzler I, Graeven U, Muller-Tidow C, Boccadoro M, Scheid C, Dimopoulos MA, Hillengass J, Weisel KC, Cavo M, Sonneveld P, Goldschmidt H. Predictors of early morbidity and mortality in newly diagnosed multiple myeloma: data from five randomized, controlled, phase III trials in 3700 patients. Leukemia. 2024 Mar;38(3):640-647. doi: 10.1038/s41375-023-02105-6. Epub 2023 Dec 7.

  PMID: 38062124 DERIVED

• Kauer J, Freundt EP, Schmitt A, Weinhold N, Mai EK, Muller-Tidow C, Goldschmidt H, Raab MS, Kriegsmann K, Sauer S. Stem cell collection after lenalidomide, bortezomib and dexamethasone plus elotuzumab or isatuximab in newly diagnosed multiple myeloma patients: a single centre experience from the GMMG-HD6 and -HD7 trials. BMC Cancer. 2023 Nov 21;23(1):1132. doi: 10.1186/s12885-023-11507-9.

  PMID: 37990162 DERIVED

• Goldschmidt H, Mai EK, Bertsch U, Fenk R, Nievergall E, Tichy D, Besemer B, Durig J, Schroers R, von Metzler I, Hanel M, Mann C, Asemissen AM, Heilmeier B, Weinhold N, Huhn S, Kriegsmann K, Luntz SP, Holderried TAW, Trautmann-Grill K, Gezer D, Klaiber-Hakimi M, Muller M, Khandanpour C, Knauf W, Scheid C, Munder M, Geer T, Riesenberg H, Thomalla J, Hoffmann M, Raab MS, Salwender HJ, Weisel KC; German-Speaking Myeloma Multicenter Group (GMMG) HD7 investigators. Addition of isatuximab to lenalidomide, bortezomib, and dexamethasone as induction therapy for newly diagnosed, transplantation-eligible patients with multiple myeloma (GMMG-HD7): part 1 of an open-label, multicentre, randomised, active-controlled, phase 3 trial. Lancet Haematol. 2022 Nov;9(11):e810-e821. doi: 10.1016/S2352-3026(22)00263-0.

  PMID: 36328040 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Lenalidomide; Bortezomib; Dexamethasone; isatuximab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Hartmut Goldschmidt, Prof. Dr.

  Med. Klinik V, University Hospital Heidelberg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Division of Multiple Myeloma

Model Details: 2 x 2 arms, 1. randomization before induction therapy (arm IA and IB), 2. randomization before maintenance therapy (arm IIA and IIB)

Study Record Dates

• First Submitted: July 24, 2018
• First Posted: August 6, 2018
• Study Start: October 18, 2018
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: February 3, 2026

Record last verified: 2026-01

Locations

DE (72)