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

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ClinicalTrials.gov Identifier: NCT03104842
Recruitment Status : Recruiting
First Posted : April 7, 2017
Last Update Posted : July 12, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital Tuebingen

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

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Isatuximab Drug: Carfilzomib Drug: Lenalidomide Drug: Dexamethasone Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 153 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Clinical Phase II, Multicenter, Open-label Study Evaluating iNduction, Consolidation and Maintenance With Isatuximab (SAR650984), Carfilzomib, LEnalidomide and Dexamethasone (I-KRd) in Primary Diagnosed High-risk Multiple Myeloma paTients
Actual Study Start Date : August 15, 2017
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : July 2024


Arm Intervention/treatment
Experimental: Arm A Transplantation
Patients ≤ 70 years of age and eligible for stem cell transplantation will enter study arm A They will undergo 6 cycles of Condolidation Treatment : Carfilzomin, Lenalidomid, Isatuximab (I-KRd), after intesification 4 cycles of I-KRd will be followed by IKR maintenance util pD or Toxicity
Drug: Isatuximab
Antibody Intravenous

Drug: Carfilzomib
Intravenous

Drug: Lenalidomide
Capsel

Drug: Dexamethasone
Capsel

Experimental: Arm B No-Transplantation
patients > 70 years or ineligible for stem cell transplantation will enter study arm B They will undergo 12 cycles of Condolidation Treatment : Carfilzomin, Lenalidomid, Isatuximab (I-KRd),to be followed by I-KR maintenance util PD or Toxicity
Drug: Isatuximab
Antibody Intravenous

Drug: Carfilzomib
Intravenous

Drug: Lenalidomide
Capsel

Drug: Dexamethasone
Capsel




Primary Outcome Measures :
  1. MRD negativity [ Time Frame: after consolidation , an average of 1 year from first dosis ]
    MRD negativity (8-color flow, Euro-Flow plus Black Swan Panel)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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
    • 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.
  2. Must be ≥ 18 years at the time of signing the informed consent form.
  3. Must be able to adhere to the study visit schedule and other protocol requirements in the investigators opinion.
  4. WHO performance status 0-3 (WHO=3 is allowed only if caused by MM and not by co-morbid conditions)
  5. 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 30 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.
  6. Females must agree to abstain from breastfeeding during study participation and 30 days* after study drug discontinuation.
  7. Males must agree to use a latex condom during any sexual contact with FCBP while participating in the study and for 90 days* following discontinuation from this study, even if he has undergone a successful vasectomy.
  8. Males must also agree to refrain from donating semen or sperm while on treatment with any study drug and for 90 days* after discontinuation from this study treatment.
  9. All subjects must agree to refrain from donating blood while on study drug and for 28 days after discontinuation from this study treatment.
  10. All subjects must agree not to share medication.
  11. All participating subjects have to follow the requirements of the Lenalidomide Pregnancy Prevention Plan

Exclusion Criteria:

  1. 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.
  2. Patients with known systemic amyloidosis (except for AL amyloidosis of the skin or the bone marrow)
  3. 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.
  4. 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)
    • Serum GOT/AST or SGPT/ALT > 3.0 x upper limit of normal (ULN) or serum total bilirubin > 2.0 mg/dL if not due to hereditary abnormalities as Gilbert's disease or hereditary hemolysis (Note: if the mentioned limits for bilirubin or ASAT/ALAT are exceeded, but there is no significant hepatic dysfunction at investigator's discretion, the Tuebingen study office has to be consulted prior to inclusion)
    • Patients with severe renal impairment (eGFR < 30 ml/min/1.73 m², MDRD formula or CDK-EPI or Creatinine Clearance < 30 ml/min)
  5. 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.
  6. 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).
  7. Acute active, uncontrolled infection
  8. Significant neuropathy (Grades 3 to 4, or Grade 2 with pain according CTC V4.03)
  9. Second malignancy within the past 5 years except:

    • adequately treated basal cell or squamous cell skin cancer
    • carcinoma in situ of the cervix
    • prostate cancer Gleason Score ≤ 6 with stable PSA over the past 12 months
    • breast carcinoma in situ with full surgical resection
    • treated medullary or papillary thyroid cancer
  10. Patients with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to study entry.
  11. Major surgery within 4 weeks prior to cycle 1 day 1 (kyphoplasty is not considered major surgery); subjects should have been fully recovered from any surgical related toxicities.
  12. Female patients who are pregnant or lactating
  13. Any other clinically significant medical disease or psychiatric condition that, in the Investigator's opinion, may interfere with protocol adherence or a patient's ability to give informed consent.
  14. Participation in any other clinical trial (with the exclusion of observational, non-interventional studies))

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): NCT03104842


Contacts
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Contact: Katja Weisel, Prof 0049 40 741058787 k.weisel@uke.de

Locations
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Germany
Vivantes Am Urban Recruiting
Berlin, Germany, 10967
Contact: Annette Dieing, MD         
Campus Benjamin Franklin Charite Berlin Recruiting
Berlin, Germany
Contact: Igor Blau, MD         
Vivantes Klinikum Neukölln Recruiting
Berlin, Germany
Contact: Maike deWit, Prof         
Städt. Kliniken Bielefeld Klinikum Mitte Recruiting
Bielefeld, Germany
Contact: Martin Görner, MD         
University Hospital Bochum Recruiting
Bochum, Germany
Contact: Ronald Schroers         
Principal Investigator: Ronald Schroers         
Johanniter-Krankenhaus Bonn Recruiting
Bonn, Germany, 53113
Contact: Yon-Dschun Ko         
Uniklinikum Chemnitz Recruiting
Chemnitz, Germany
Contact: Mathias Haenel         
Principal Investigator: Mathias Haenel, Dr.         
St. Antonius Hospital Recruiting
Eschweiler, Germany
Contact: Hildegard Neuelen       Hildegard.Neulen@sah-eschweiler.de   
Principal Investigator: Staib, Dr         
Universitätsklinikum Essen Recruiting
Essen, Germany
Contact: Jan Dürig, MD         
Asklepios Altona Recruiting
Hamburg, Germany
Contact: Buß       d.buss@asklepios.de   
Principal Investigator: Salwender, Dr.         
University Hospital Hamburg Eppendorf Recruiting
Hamburg, Germany
Contact: Jannina Schlüter       Ja.Schlueter@uke.de   
Principal Investigator: Katja Weisel, Prof         
University Hospital Heidelberg Recruiting
Heidelberg, Germany
Contact: Hartmut Goldschmidt, Prof         
Uniklinik Köln Recruiting
Koln, Germany
Contact: Christoph Scheid, MD         
Universitätsmedizin der Johannes Gutenberg-Universität Mainz Recruiting
Mainz, Germany, D-55131
Contact: Markus M Munder, MD         
Philipps-Universität Marburg Recruiting
Marburg, Germany, 35032
Contact: Andreas Neubauer, MD         
Klinik für Hämatologie, Onkologie und GastroenterologieKliniken Maria Hilf GmbH Recruiting
Mönchengladbach, Germany, 41063
Contact: Ullrich Graeven         
University Hospital Münster Not yet recruiting
Münster, Germany
Contact: Julia Reusch         
Principal Investigator: Julia Reusch, DR         
Zentrum für Tumordiagnostik und -therapieHämatologie/Int. Onkologie Recruiting
Osnabruck, Germany
Contact: Rudolf Peceny, MD         
Universitätsklinikum Tuebingen Recruiting
Tuebingen, Germany
Contact: Loreen Degen         
Principal Investigator: Britta Besemer, DR         
Sponsors and Collaborators
University Hospital Tuebingen
Investigators
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Principal Investigator: Katja Weisel, Prof Universitätsklinikum Hamburg-Eppendorf

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Responsible Party: University Hospital Tuebingen
ClinicalTrials.gov Identifier: NCT03104842     History of Changes
Other Study ID Numbers: GMMG-CONCEPT
First Posted: April 7, 2017    Key Record Dates
Last Update Posted: July 12, 2019
Last Verified: July 2018
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
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
Dexamethasone acetate
Lenalidomide
BB 1101
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
Protease Inhibitors