Isatuximab in combination with Lenalidomide-Dexamethasone compared to Lenalidomide-Dexamethasone in elderly patients (aged ≥70 years) with newly diagnosed myeloma: a randomized phase II study (SGZ-2019-12650)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Arbeitsgemeinschaft Medikamentoese Tumortherapie gGmbH

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

20 Oct 2021 → ongoing

Decision date (initial)

2024-11-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Sanofi-aventis GmbH Austria

External identifiers

EU CT number

2024-515581-13-00

EudraCT number

2020-004972-17

ClinicalTrials.gov

NCT04891809

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To demonstrate the benefit of isatuximab in combination with lenalidomide and low-dose dexamethasone followed by isatuximab and lenalidomide maintenance therapy in increasing the proportion of patients with MRD negativity as compared to lenalidomide and low-dose dexamethasone followed by lenalidomide maintenance treatment in patients with newly diagnosed multiple myeloma (NDMM).

Secondary objectives 9

1. To evaluate the Overall Response Rate (ORR), Partial Response (PR), Very Good Partial Response (VGPR) and Complete Response (CR) as per International Myeloma Working Group (IMWG) criteria in each arm.
2. To compare the Progression-free (PFS) and Overall Survival (OS) between the two arms.
3. To evaluate the proportion of patients with MRD negativity (defined by NGF at 10^-5) after 12 months (13 cycles) of maintenance treatment.
4. To evaluate the Time to Progression (TTP) in each arm.
5. To evaluate the PFS in high risk cytogenetic population defined as patients carrying a) del(17p), t(4;14), t(14;16) in each arm and b) the same aberrations plus amp1q21.
6. To evaluate the Duration of Response in each arm.
7. To evaluate safety in both treatment arms.
8. To assess disease-specific and a generic health-related quality of life (HRQL), disease and treatment-related symptoms, health state utility and health status.
9. To evaluate PFS of potential second line therapy.

Conditions and MedDRA coding

Isatuximab in combination with Lenalidomide-Dexamethasone compared to Lenalidomide-Dexamethasone in elderly patients (aged ≥70 years) with newly diagnosed myeloma: a randomized phase II study (SGZ-2019-12650)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age ≥ 70 years
2. Able to provide written informed consent in accordance with federal, local, and institutional guidelines
3. Patients must have newly diagnosed, symptomatic multiple myeloma with evidence of measurable disease (assessed within 21 days prior to randomization) o Serum M protein ≥0.5 g/dL measured using serum protein immunoelectrophoresis and/or o Urine M protein ≥200 mg/24 hours measured using urine protein immunoelectrophoresis and/or o In subjects without detectable serum or urine M-protein, serum free light chain (SFLC) ≥100 mg/L (involved light chain) and an abnormal FLC ratio
4. No prior treatment for multiple myeloma
5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2
6. Patients at cardiac risk (NYHA >ll) or pre-existing coronary heart disease, or any other clinically relevant cardiac complication) should be scheduled for a baseline ECHO and can only be included if the LVEF is >40%
7. Adequate organ and bone marrow function within the 21 days prior to randomization defined by: o Bilirubin < 2 times the upper limit of normal (ULN), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times the ULN o Absolute neutrophil count (ANC) ≥ 750/mm3 (growth factor support for max 3 days allowed to achieve this value) o Hemoglobin >8.0 g/dL (Use of erythropoietic stimulating factors and red blood cell [RBC] transfusion per institutional guidelines is allowed, however the most recent RBC transfusion may not have been done within 7 days prior to obtaining screening hemoglobin.) o Platelet count >50,000/mm3 o Calculated or measured creatinine clearance (CrCl) of ≥30 mL/min/1.73m2 (Calculation should be based on the MDRD formula (age, gender, black/non- black, weight, height)

Exclusion criteria 20

1. ECOG status >2
2. Patients unlikely to tolerate Rd
3. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
4. Plasma cell leukemia (> 2.0 x 10^9/L circulating plasma cells by standard differential)
5. Myelodysplastic syndrome
6. Smoldering Myeloma and MGUS
7. Second malignancy within the past 5 years except: o Adequately treated basal cell or squamous cell skin cancer o Carcinoma in situ of the cervix o Prostate cancer ≤ Gleason score 6 with stable prostate-specific antigen (PSA over 12 months) o Ductal breast carcinoma in situ with full surgical resection (i.e., negative margins) o Treated medullary or papillary thyroid cancer o Other tumors with low risk of recurrence/metastases and/or early stage R0 surgery
8. History of or current amyloidosis
9. Glucocorticoid therapy within the 14 days prior to randomization that exceeds an accumulated dose of 160 mg dexamethasone or 1000 mg prednisone
10. Extended field radio therapy (more than 3 fields) within the 21 days prior to randomization
11. Contraindication to isatuximab, dexamethasone, lenalidomide or any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs
12. Active congestive heart failure (New York Heart Association [NYHA] Class III or IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, acute diffuse infiltrative pulmonary disease, pericardial disease, or myocardial infarction within 4 months prior to enrolment
13. Active infection within the 14 days prior to randomization requiring systemic antibiotics and/or antiviral therapy
14. Uncontrolled hypertension or uncontrolled diabetes despite medication
15. Significant neuropathy (Grade 2 with pain or Grade 3 or higher) within the 14 days prior to randomization
16. Known cirrhosis
17. Known human immunodeficiency virus (HIV) seropositivity or active hepatitis C or hepatitis B infection (subjects with past hepatitis B virus [HBV] infection or resolved HBV infection defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti HBc] antibody test are eligible; subjects positive for hepatitis C virus [HCV] antibody are eligible only if polymerase chain reaction [PCR] is negative for HCV RNA.)
18. Participation in another interventional study within the 28 days prior to randomization
19. Major surgery (except kyphoplasty) within the 28 days prior to randomization
20. Any other clinically significant medical disease or social condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent, be compliant with study procedures, or provide accurate information.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To evaluate the proportion of patients with MRD negativity (defined by NGF (next generation flow) at 10^-5) after end of induction treatment in the two arms.

Secondary endpoints 9

1. To evaluate the Overall Response Rate (ORR), Partial Response (PR), Very Good Partial Response (VGPR) and Complete Response (CR) as per International Myeloma Working Group (IMWG) criteria in each arm.
2. To compare the Progression-free (PFS) and Overall Survival (OS) between the two arms.
3. To evaluate the proportion of patients with MRD negativity (defined by NGF at 10^-5) after 12 months (13 cycles) of maintenance treatment.
4. To evaluate the Time to Progression (TTP) in each arm.
5. To evaluate the PFS in high risk cytogenetic population defined as patients carrying a) del(17p), t(4;14), t(14;16) in each arm and b) the same aberrations plus amp1q21.
6. To evaluate the Duration of Response in each arm.
7. To evaluate safety in both treatment arms.
8. To assess disease-specific and a generic health-related quality of life (HRQL), disease and treatment-related symptoms, health state utility and health status.
9. To evaluate PFS of potential second line therapy.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Arbeitsgemeinschaft Medikamentoese Tumortherapie gGmbH

Sponsor organisation

Arbeitsgemeinschaft Medikamentoese Tumortherapie gGmbH

Address

Gentzgasse 60/21, Waehring Waehring

City

Vienna

Postcode

1180

Country

Austria

Scientific contact point

Organisation

Arbeitsgemeinschaft Medikamentoese Tumortherapie gGmbH

Contact name

Clinical Trials Lead Manager

Public contact point

Organisation

Arbeitsgemeinschaft Medikamentoese Tumortherapie gGmbH

Contact name

Clinical Trials Lead Manager

Third parties 4

Locations

2 EU/EEA countries · 12 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 22 files

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

Application history

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