Clinical Trials /

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

NCT03104842

Description:

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

Related Conditions:
  • Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Evaluation iNduction, Consolidation and Maintenance Treatment With Isatuximab , Carfilzomib, LEnalidomide and Dexamethasone
  • 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

Clinical Trial IDs

  • ORG STUDY ID: GMMG-CONCEPT
  • NCT ID: NCT03104842

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
IsatuximabArm A Transplantation
CarfilzomibArm A Transplantation
LenalidomideArm A Transplantation
DexamethasoneArm A Transplantation

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Arm A TransplantationExperimentalPatients ≤ 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
  • Isatuximab
  • Carfilzomib
  • Lenalidomide
  • Dexamethasone
Arm B No-TransplantationExperimentalpatients > 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
  • Isatuximab
  • Carfilzomib
  • Lenalidomide
  • Dexamethasone

Eligibility 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))
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:MRD negativity
Time Frame:after consolidation , an average of 1 year from first dosis
Safety Issue:
Description:MRD negativity (8-color flow, Euro-Flow plus Black Swan Panel)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University Hospital Tuebingen

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