Compare Lenalidomide and Subcutaneous Daratumumab vs Lenalidomide and Dexamethasone in Frail Subjects With Previously Untreated Multiple Myeloma Who Are Ineligible for High Dose Therapy

Multiple Myeloma Clinical Trial

— IFM2017_03  

Official title:

A Phase III Study Comparing Lenalidomide and Subcutaneous Daratumumab (R-Dara SC) vs Lenalidomide and Dexamethasone (Rd) in Frail Subjects With Previously Untreated Multiple Myeloma Who Are Ineligible for High Dose Therapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03993912
• Other study ID #: 2018_16
• Secondary ID: 2018-003535-30
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 17, 2019
• Est. completion date: October 2027

Study information

• Verified date: March 2024
• Source: University Hospital, Lille
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 3, randomized (study drug assigned by chance), open-label (participants and researchers are aware about the treatment, participants are receiving), active-controlled (study in which the experimental treatment or procedure is compared to a standard treatment or procedure), parallel-group (each group of participants will be treated at the same time), and multicenter (when more than one hospital team work on a medical research study) study in participants with newly diagnosed multiple myeloma (a blood cancer of plasma cells) and who are not candidates for high dose chemotherapy (treatment of disease, usually cancer, by chemical agents) and autologous stem cell transplant (ASCT). The primary hypothesis of this study is that subcutaneous Daratumumab in combination with Lenalidomide will prolong progression-free survival and likely induce less toxicity as compared with Lenalidomide and dexamethasone, in elderly frail subjects with newly diagnosed Multiple myeloma who are ineligible for high dose chemotherapy and ASCT

Description:

The primary hypothesis of this study is that subcutaneous Daratumumab in combination with Lenalidomide will prolong progression-free survival and likely induce less toxicity as compared with Lenalidomide and dexamethasone, in elderly frail subjects with newly diagnosed Multiple myeloma who are ineligible for high dose chemotherapy and ASCT

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 294
• Est. completion date: October 2027
• Est. primary completion date: October 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

1. Subject must be at least 65 years of age.

2. Subject must have documented multiple myeloma satisfying the CRAB criteria and measurable disease.

3. Newly diagnosed and not considered candidate for high-dose chemotherapy with SCT.

4. Subject must have a Frailty Score = 2

5. Subject must have within 5 days prior to first drug intake (C1D1) pretreatment clinical laboratory values meeting the following criteria during the Screening Phase:

• hemoglobin =7.5 g/dL

• absolute neutrophil count =1.0 x 109/L

• platelet count =70 x 109/L

• aspartate aminotransferase (AST) =2.5 x upper limit of normal (ULN)

• alanine aminotransferase (ALT) =2.5 x ULN

• total bilirubin =2.0 x ULN

• creatinine clearance=30mL/min

6. Measurable ISS with ß2-microglobulin and albumin values for randomization

7. A man who is sexually active with a woman of childbearing potential must agree to use a latex or synthetic condom, even if they had a successful vasectomy. All men must also not donate sperm during the study, for 4 weeks after the last dose of lenalidomide, and for 4 months after the last dose of daratumumab. Women participating in this study must be postmenopausal.

8. Each subject must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study. Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol, as referenced in the ICF.

9. Subjects affiliated with an appropriate social security system.

Exclusion Criteria:

1. Subject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma.

2. Subject has a diagnosis of Waldenström's disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.

3. Subject has prior or current systemic therapy or SCT for multiple myeloma

4. Subject has a history of malignancy (other than multiple myeloma) within 5 years before the date of randomization

5. Subject has had radiation therapy within 14 days of randomization.

6. Subject has had plasmapheresis within 28 days of randomization.

7. Subject is exhibiting clinical signs of meningeal involvement of multiple myeloma.

8. Subject has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume [FEV] in 1 second <60% of predicted normal), persistent asthma, or a history of asthma within the last 2 years (intermittent asthma is allowed).

9. Subject is known to be seropositive for history of human immunodeficiency virus (HIV)

10. Seropositive for hepatitis B.

11. (Known to be) seropositive for hepatitis C

12. Subject has any concurrent medical or psychiatric condition or disease that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study.

13. Subject has clinically significant cardiac disease, including:

• myocardial infarction within 1 year before randomization, or an unstable or uncontrolled disease/condition related to or affecting cardiac function

• uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities

• screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >470 msec

14. Subject has known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients

15. Subject has plasma cell leukemia or POEMS syndrome

16. Subject is known or suspected of not being able to comply with the study protocol. Subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject or that could prevent, limit, or confound the protocol-specified assessments.

17. Subject has had major surgery within 2 weeks before randomization or has not fully recovered from surgery.

18. Subject has received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 4 weeks before randomization or is currently enrolled in an interventional investigational study.

19. Refusal to consent or protected by legal regime ( guardianship, trusteeship)

20. Subject has contraindications to required prophylaxis for deep vein thrombosis and pulmonary embolism

21. Incidence of gastrointestinal disease that may significantly alter the absorption of oral drugs.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Daratumumab SC in combination with Lenalidomide
Daratumumab SC 1800 mg once every week for 8 weeks then once every other week for 16 weeks thereafter once every 4 weeks, until progression
• Lenalidomide PO (25mg)
Lenalidomide PO (25mg): days 1 through 21 of each 28-day cycle, until progression
• Dexamethasone PO (20mg): days 1, 8, 15, 22 of each 28-day cycle, until progression
Dexamethasone PO (20mg): days 1, 8, 15, 22 of each 28-day cycle, until progression

Locations

Country	Name	City	State
France	Chru Jean Minjoz	Besançon
France	Ch Blois Simone Veil	Blois
France	Ch Fleyriat	Bourg-en-Bresse
France	Chru Brest Site Hopital Morvan	Brest
France	Chu de Caen Normandie	Caen
France	Hopital Prive Sevigne - Cesson	Cesson-Sévigné
France	Chu Dijon Bourgogne	Dijon
France	Chu de Grenoble	Grenoble
France	Gpe Hospitalier La Rochelle-Re-Aunis	La Rochelle
France	Ch Chartres Louis Pasteur-Le Coudray	Le Coudray
France	Hôpital Claude Huriez, CHU	Lille
France	Institut Paoli Calmettes	Marseille
France	Chi Mont de Marsan Et Pays Des Sources	Mont-de-Marsan
France	Chu Montpellier	Montpellier
France	Chu de Nantes Site Hotel Dieu Hme	Nantes
France	Chu de Nice Hopital de L'Archet	Nice
France	Centre Hospitalier de Perigueux	Périgueux
France	Hopital Haut-Leveque - Chu	Pessac
France	Chru Rennes Site Pontchaillou	Rennes
France	Centre Hospitalier Saint-Malo	Saint-Malo
France	Centre Hospitalier de Saint Quentin	Saint-Quentin
France	Oncopole Chu Toulouse	Toulouse
France	Chu de Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Lille

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of the efficacy of Daratumumab SC injection when combined with Lenalidomide (R-Dara SC) vs Lenalidomide and Dexamethasone (Rd): PFS	The primary objective is to compare the efficacy of Daratumumab SC injection when combined with Lenalidomide (R-Dara SC) to that of Lenalidomide and Dexamethasone (Rd), in terms of PFS in frail subjects with newly diagnosed myeloma who are not candidates for high dose chemotherapy and autologous stem cell transplant.	From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
Secondary	Time-to-treatment failure		From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
Secondary	Time-to-next treatment		From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
Secondary	PFS2 time		From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
Secondary	Overall survival (OS) time	Overall survival (OS) time,	From date of randomization until the date of death from any cause, whichever came first, assessed up to 84months
Secondary	Complete remission (CR)	Percentage of participants with CR, as defined by the IMWG criteria, will be reported.	From date of randomization until the date of first documented progression whichever came first, assessed up to 84months
Secondary	Very good partial response (VGPR) or better.	VGPR or better, defined as VGPR or CR according to the IMWG criteria during or after the study treatment at the time of data cutoff.	From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
Secondary	Overall response (CR + VGPR + partial response [PR]).	Overall response, defined as CR or VGPR or PR, according to the IMWG criteria	From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
Secondary	Occurrence of grade 3 or more side effects.	Collecting all AE (grade 3 or more)	From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
Secondary	Safety and tolerability of Daratumumab SC when administered in combination with Revlimid: NCI-CTCAE V5.0.	Evaluation of safety data by type, frequency, severity, relation to study drug, according to NCI-CTCAE V5.0.	From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
Secondary	Evaluation of quality of life based on MY20 questionnaires	Treatment effects on patient reported outcomes and heath economic/resource utilization.	From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
Secondary	Evaluation of quality of life based on EORTC C30 questionnaires	Treatment effects on patient reported outcomes and heath economic/resource utilization.	From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
Secondary	Evaluation of quality of life based on EQ-5D questionnaires	Treatment effects on patient reported outcomes and heath economic/resource utilization.	From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
Secondary	Minimal residual disease (MRD) negative rate at 12 months.	Proportion of participants assessed as MRD negative	after 12 months of treatment
Secondary	Event Free Survival		From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months