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 GMMG-CONCEPT

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Medical Center Hamburg-Eppendorf

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

15 Aug 2017 → ongoing

Decision date (initial)

2024-09-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Amgen Limited · Sanofi-Aventis Recherche & Development · Celgene International II Sárl

External identifiers

EU CT number

2024-511791-32-00

EudraCT number

2016-000432-17

ClinicalTrials.gov

NCT03104842

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To evaluate MRD negativity (8 color flow) after consolidation (10 I-KRd cycles including intensification in transplant-eligible and 12 I-KRd cycles in transplant-ineligible patients) with a sensitivity of 10-5.

Secondary objectives 2

1. To evaluate progression-free survival (PFS)
2. • To evaluate Overall Response Rate (ORR) • To assess duration of minimal residual disease state • To evaluate overall survival • To assess time to subsequent therapy• To evaluate progression-free survival on next line therapy (PFS2) • To assess time to myeloma response • Quality of life assessment of patients at baseline, during induction treatment, consolidation and maintenance treatment

Conditions and MedDRA coding

Multiple Myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 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) 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 investigator’s 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. (1) 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

1. 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: o Absolute neutrophil count (ANC) < 1,000/μL, unless related to myeloma o Platelet count < 30,000/ μL (in case of platelets < 50.000 /µL and ≥ 30.000 /µL myeloma bone marrow infiltration should be ≥ 50%) o Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L); or free ionized calcium > 6.5 mg/dL (> 1.6 mmol/L) o 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) o 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). Patients with a history of hepatitis B infection have to be monitored repetitively during treatment. In case of signs of hepatitis B reactivation, antiviral treatment has to be initiated and patients have to be referred to a specialist for treatment and monitoring of hepatitis infection. 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. MRD negativity (sensitivity 10^-5, NGF) after consolidaton

Secondary endpoints 1

1. Progression free survival

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Medical Center Hamburg-Eppendorf

Sponsor organisation

University Medical Center Hamburg-Eppendorf

Address

Martinistrasse 52, Eppendorf Eppendorf

City

Hamburg

Postcode

20251

Country

Germany

Scientific contact point

Organisation

University Medical Center Hamburg-Eppendorf

Contact name

Prof. Dr. med. Katja Weisel

Public contact point

Organisation

University Medical Center Hamburg-Eppendorf

Contact name

Prof. Dr. med. Katja Weisel

Locations

1 EU/EEA country · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications