Evaluation iNduction, Consolidation and Maintenance Treatment With Isatuximab , Carfilzomib, LEnalidomide and Dexamethasone

NCT03104842 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: GMMG-CONCEPT
• Study Type: interventional
• Target: 246
• Locations: 1 country
• Sites: 17

Brief Summary

A Clinical Phase II, multicenter, Open-label study evaluating iNduction, consolidation and maintenance treatment with Isatuximab (SAR650984), Carfilzomib, LEnalidomide and Dexamethasone (I-KRd) in Primary diagnosed high-risk multiple myeloma paTients

Conditions

Multiple Myeloma

Keywords

Cytogenetic High-Risk

Outcome Measures

Primary Outcomes (1)

• MRD negativity

  MRD negativity (8-color flow, Euro-Flow plus Black Swan Panel)

  after consolidation , an average of 1 year from first dosis

Study Arms (2)

Arm A Transplantation

EXPERIMENTAL

Patients ≤ 70 years of age and eligible for stem cell transplantation will enter study arm A They will undergo 6 cycles of Induction Treatment : Carfilzomib, Lenalidomid, Isatuximab (I-KRd), after intensification another 4 cycles of I-KRd as consolidation will be followed by IKR maintenance until PD or Toxicity

Drug: Isatuximab; Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone

Arm B No-Transplantation

EXPERIMENTAL

Patients \> 70 years or ineligible for stem cell transplantation will enter study arm B They will undergo 12 cycles of Treatment : Carfilzomib, Lenalidomid, Isatuximab (I-KRd) (6 Cycles Induction, 2 Cycles Intensification, 4 Cycles Consolidation),to be followed by I-KR maintenance util PD or Toxicity

Drug: Isatuximab; Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Isatuximab DRUG

Antibody Intravenous

Arm A Transplantation; Arm B No-Transplantation

Carfilzomib DRUG

Intravenous

Arm A Transplantation; Arm B No-Transplantation

Lenalidomide DRUG

Capsel

Arm A Transplantation; Arm B No-Transplantation

Dexamethasone DRUG

Capsel

Arm A Transplantation; Arm B No-Transplantation

Eligibility Criteria

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

You may qualify if:

• Subjects must have newly diagnosed, untreated, symptomatic (according to the revised CRAB criteria 2014), documented myeloma and have measurable disease (serum M-protein ≥ 1 g/dL (for IgA ≥ 0.5 g/dL) or urine M-protein ≥ 200 mg/24 hours) or in case of oligosecretory myeloma: involved FLC level ≥ 10 mg/dl, provided sFLC ratio is abnormal or in case of asecretory myeloma: \> 1 focal lesions measurable by MRI
• Subjects must have high-risk myeloma defined as followed:
• Presence of one or more of the following cytogenetic abnormalities (determined by FISH):
• Del(17p) in ≥ 10% of purified cells
• t(4;14)
• ≥ 3 copies +1q21
• t(14;16)
• ISS Stage II or III (all patients)
• FISH analysis of external laboratories other than Heidelberg is accepted, a list of laboratories will be filed in the study central.
• Must be ≥ 18 years at the time of signing the informed consent form.
• Must be able to adhere to the study visit schedule and other protocol requirements in the investigators opinion.
• WHO performance status 0-3 (WHO=3 is allowed only if caused by MM and not by co-morbid conditions)
• Females of childbearing potential (FCBP) (1) must agree to refrain from becoming pregnant for 28 days prior to initiation of study drug, while on study drug and for 150 days\* after discontinuation from the study drug by using 2 reliable methods of contraception and must agree to regular pregnancy testing during this timeframe.
• A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., who has had menses at any time in the preceding 24 consecutive months) 3) has achieved menarche at some point.
• Females must agree to abstain from breastfeeding during study participation and 30 days\* after study drug discontinuation.

You may not qualify if:

• Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize Carfilzomib), mannitol, sucrose, histidine (as base and hydrochloride salt) and polysorbate 80 or any of the components of study therapy that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents.
• Patients with known systemic amyloidosis (except for AL amyloidosis of the skin or the bone marrow)
• Administration of systemic chemotherapy, biological, immunotherapy or any investigational agent (therapeutic or diagnostic) for multiple myeloma except bisphosphonate therapy. Emergency treatment with dexamethasone is allowed when the cumulative dexamethasone dose is less or equal 160 mg. It is allowed to include patients in the trial after 1 cycle (4 weeks) of any anti-myeloma first-line treatment.
• Any of the following laboratory abnormalities:
• Absolute neutrophil count (ANC) \< 1,000/μL, unless related to myeloma
• Platelet count \< 30,000/ μL (in case of platelets \< 50.000 /µl and ≥ 30.000 /µl myeloma bone marrow infiltration should be ≥ 50%)
• Corrected serum calcium \> 14 mg/dL (\> 3.5 mmol/L); or free ionized calcium \> 6.5 mg/dL (\> 1.6 mmol/L)
• Patients with severe renal impairment (eGFR \< 30 ml/min/1.73 m², MDRD formula or CDK-EPI or Creatinine Clearance \< 30 ml/min)
• Active congestive heart failure (NYHA Class III to IV), symptomatic cardiac ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within four months prior study entry.
• Known HIV seropositive, hepatitis C infection, and/or hepatitis B (except for patients with hepatitis B sAg and core antibody receiving and responding to antiviral therapy directed at hepatitis B: these patients are allowed).
• Acute active, uncontrolled infection
• Significant neuropathy (Grades 3 to 4, or Grade 2 with pain according CTC V4.03)
• Second malignancy within the past 5 years except:
• adequately treated basal cell or squamous cell skin cancer
• carcinoma in situ of the cervix

Sponsors & Collaborators

• Universitätsklinikum Hamburg-Eppendorf: lead

Study Sites (17)

Vivantes Am Urban

Berlin, 10967, Germany

Location

Campus Benjamin Franklin Charite Berlin

Berlin, Germany

Location

Vivantes Klinikum Neukölln

Berlin, Germany

Location

Städt. Kliniken Bielefeld Klinikum Mitte

Bielefeld, Germany

Location

Johanniter-Krankenhaus Bonn

Bonn, 53113, Germany

Location

Uniklinikum Chemnitz

Chemnitz, Germany

Location

Uniklinik Köln

Cologne, Germany

Location

St. Antonius Hospital

Eschweiler, Germany

Location

Universitätsklinikum Essen

Essen, Germany

Location

Asklepios Altona

Hamburg, Germany

Location

University Hospital Hamburg Eppendorf

Hamburg, Germany

Location

University Hospital Heidelberg

Heidelberg, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, D-55131, Germany

Location

Philipps-Universität Marburg

Marburg, 35032, Germany

Location

Kliniken Maria Hilf GmbH, Klinik für Hämatologie, Onkologie und Gastroenterologie

Mönchengladbach, 41063, Germany

Location

Klinikum Osnabrück

Osnabrück, Germany

Location

Universitätsklinikum Tuebingen

Tübingen, Germany

Location

Related Publications (5)

• Leypoldt LB, Besemer B, Asemissen AM, Hanel M, Blau IW, Gorner M, Ko YD, Reinhardt HC, Staib P, Mann C, Lutz R, Munder M, Graeven U, Peceny R, Salwender H, Jauch A, Zago M, Benner A, Tichy D, Bokemeyer C, Goldschmidt H, Weisel KC. Isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in front-line treatment of high-risk multiple myeloma: interim analysis of the GMMG-CONCEPT trial. Leukemia. 2022 Mar;36(3):885-888. doi: 10.1038/s41375-021-01431-x. Epub 2021 Nov 3. No abstract available.

  PMID: 34732857 RESULT

• Leypoldt LB, Tichy D, Besemer B, Hanel M, Raab MS, Mann C, Munder M, Reinhardt HC, Nogai A, Gorner M, Ko YD, de Wit M, Salwender H, Scheid C, Graeven U, Peceny R, Staib P, Dieing A, Einsele H, Jauch A, Hundemer M, Zago M, Pozek E, Benner A, Bokemeyer C, Goldschmidt H, Weisel KC. Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone for the Treatment of High-Risk Newly Diagnosed Multiple Myeloma. J Clin Oncol. 2024 Jan 1;42(1):26-37. doi: 10.1200/JCO.23.01696. Epub 2023 Sep 27.

  PMID: 37753960 RESULT

• Leypoldt LB, Tichy D, Besemer B, Hanel M, Raab MS, Mann C, Munder M, Reinhardt HC, Nogai A, Gorner M, Ko YD, de Wit M, Salwender H, Scheid C, Graeven U, Peceny R, Staib P, Dieing A, Einsele H, Jauch A, Hundemer M, Zago M, Pozek E, Benner A, Bokemeyer C, Goldschmidt H, Weisel KC. Plain language summary of isatuximab plus carfilzomib, lenalidomide, and dexamethasone for the treatment of people with high-risk newly diagnosed multiple myeloma. Future Oncol. 2024 Dec;20(39):3193-3207. doi: 10.1080/14796694.2024.2402639. Epub 2024 Sep 30.

  PMID: 39345094 DERIVED

• Oliva S, Kaiser MF. Is it time to tailor treatment on the basis of minimal residual disease in multiple myeloma? Lancet Haematol. 2021 Dec;8(12):e876-e877. doi: 10.1016/S2352-3026(21)00341-0. No abstract available.

  PMID: 34826409 DERIVED

• Pawlyn C. High-risk myeloma: a challenge to define and to determine the optimal treatment. Lancet Haematol. 2021 Jan;8(1):e4-e6. doi: 10.1016/S2352-3026(20)30361-6. Epub 2020 Dec 22. No abstract available.

  PMID: 33357481 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

isatuximab; carfilzomib; Lenalidomide; Dexamethasone

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; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Katja Weisel, Prof

  Universitätsklinikum Hamburg-Eppendorf

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2017
• First Posted: April 7, 2017
• Study Start: August 15, 2017
• Primary Completion: May 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: May 15, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (17)