Free regimen of Dexamethasone as initial therapy for advanced relapsed/refractory multiple myeloma: an open-label randomized, non-inferiority, controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

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

12 Dec 2024 → ongoing

Decision date (initial)

2024-07-23

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-510981-18-00

ClinicalTrials.gov

NCT06561854

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To determine the overall response rate (ORR) after six cycles of salvage therapy assessed with the International Myeloma Working Group (IMWG) criteria.

Secondary objectives 1

1. • Best ORR, defined as the proportion of subjects who achieve CR or PR according to the IMWG criteria, at any time point following salvage therapy. • Time to progression (TTP) • Progression-free survival (PFS) defined as the duration from the date of randomization to either progressive disease, according to the IMWG criteria, or death, at 2 years after randomization. • OS defined as the duration from the date of randomization to death, at 2 years after randomization. • Incidence of adverse events (AE) within the 2 years after randomization. • Quality of Life (QoL) within the 2 years after randomization.

Conditions and MedDRA coding

Multiple Myeloma Multiple myeloma (MM) is a B cell malignancy and is one of the most frequent primary neoplasms of the bone marrow

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. • Adult patients (≥18 years old) • Documented MM in relapse according to standard criteria. • All patients must have received between 1 to 3 prior therapies for MM (a prior therapy is defined as 2 or more cycles of therapy given as a MM treatment plan • Eligible for one of the following antibody-based approved combinations (see 2.6 for details on EMEA authorization): (1) ICARIA schema: isatuximab, pomalidomide and dexamethasone. (2) IKEMA schema: isatuximab, carfilzomib and dexamethasone • Subject must have achieved a response (PR or better) to the prior regimen. • ECOG Performance Status score of 0, 1, or 2. • For subjects experiencing toxicities resulting from previous therapy (including peripheral neuropathy), the toxicities must have been resolved or stabilized. • Signed informed consent

Exclusion criteria 1

1. • Contraindications to investigational medicinal products or auxiliary medicinal product • Evidence of refractoriness or intolerance to anti-CD38 monoclonal antibodies or if the patient received an anti-CD38 within the last 6 months. • Previous treatment according to the ICARIA schema with pomalidomide orIKEMA schema with carfilzomib • Allogenic hematopoietic cell transplant (HCT, regardless of timing). • Planned to undergo an HCT prior to progression of disease ie, these patients should not be enrolled in order to reduce disease burden prior to transplant. • History of malignancy (other than MM) within 3 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix, or malignancy that in the opinion of the Investigator is considered cured with minimal risk of recurrence within 3 years). • Known MM meningeal Involvement. • Plasma cell leukemia (>2.0 × 109/L circulating plasma cells by standard differential) or Waldenström’s macroglobulinemia or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or amyloidosis. • Any concurrent medical condition or disease (e.g., active systemic infection) that is likely to interfere with study procedures or results, or that, in the opinion, of the Investigator would constitute a hazard by participating in this study. • Uncontrolled chronic obstructive pulmonary disease (COPD) • Clinically significant cardiac disease. • Seropositive for hepatitis B with positive PCR • Seropositive for human immunodeficiency virus (HIV) or hepatitis C. • Creatinine clearance ≤30 mL/min • Pregnancy or absence of effective contraceptive method for women of childbearing potential • Lactation • Participation to another interventional clinical trial except with the agreement of the coordinating investigator.• Inability to give written informed consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. the ORR after six cycles of salvage therapy, defined as the proportion of subjects who achieve complete response (CR) or partial response (PR) according to the IMWG criteria, following salvage therapy.

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Mohty

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Prof Mohamad Mohty

Sponsor responsibilities

Article 77 compliance

Assistance Publique Hopitaux De Paris

Contact point sponsor

Assistance Publique Hopitaux De Paris

Article 77 implementation

Assistance Publique Hopitaux De Paris

Locations

1 EU/EEA country · 46 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 11 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