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

Multiple Myeloma Clinical Trial

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03104842
• Other study ID #: GMMG-CONCEPT
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 15, 2017
• Est. completion date: September 2026

Study information

• Verified date: May 2024
• Source: Universitätsklinikum Hamburg-Eppendorf
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 246
• Est. completion date: September 2026
• Est. primary completion date: May 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

• 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.

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 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.

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 150 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 150 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 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))

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Isatuximab
Antibody Intravenous
• Carfilzomib
Intravenous
• Lenalidomide
Capsel
• Dexamethasone
Capsel

Locations

Country	Name	City	State
Germany	Campus Benjamin Franklin Charite Berlin	Berlin
Germany	Vivantes Am Urban	Berlin
Germany	Vivantes Klinikum Neukölln	Berlin
Germany	Städt. Kliniken Bielefeld Klinikum Mitte	Bielefeld
Germany	Johanniter-Krankenhaus Bonn	Bonn
Germany	Uniklinikum Chemnitz	Chemnitz
Germany	St. Antonius Hospital	Eschweiler
Germany	Universitätsklinikum Essen	Essen
Germany	Asklepios Altona	Hamburg
Germany	University Hospital Hamburg Eppendorf	Hamburg
Germany	University Hospital Heidelberg	Heidelberg
Germany	Uniklinik Köln	Koln
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz
Germany	Philipps-Universität Marburg	Marburg
Germany	Kliniken Maria Hilf GmbH, Klinik für Hämatologie, Onkologie und Gastroenterologie	Mönchengladbach
Germany	Klinikum Osnabrück	Osnabrück
Germany	Universitätsklinikum Tuebingen	Tuebingen

Sponsors (1)

Lead Sponsor	Collaborator
Universitätsklinikum Hamburg-Eppendorf

Country where clinical trial is conducted

Germany, 

References & Publications (2)

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, — View Citation

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, G — View Citation

Outcome

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