Study Comparing Therapy for Advanced Relapsed/Refractory Multiple Myeloma With and Without Dexamethasone

NCT06561854 | Recruiting Phase 3

• 2 other identifiers: APHP2310892024-510981-18-00
• Study Type: interventional
• Target: 318
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with relapsed/refractory symptomatic multiple myeloma who meet all inclusion criteria, will be randomized 1:1 to receive either standard of care chemotherapy (IKEMA or ICARIA) and dexamethasone until disease progression ("dexamethasone arm", arm A) or standard of care chemotherapy (IKEMA or ICARIA) and dexamethasone with dexamethasone discontinuation from the 3rd cycle of treatment (after 8 weeks) ("dexamethasone-free arm", arm B). In most centers, IKEMA and ICARIA schema can be adapted according to the standard of care in each center Choice between the ICARIA and IKEMA schema is at the discretion of the investigator, in compliance with each drug's SmPC, but must be performed before randomisation for the purpose of stratification.

Conditions

Multiple Myeloma; Relapse Multiple Myeloma

Keywords

Multiple myeloma; Relapse; Dexamethasone; Isatuximab; Pomalidomide; Carfilzomib

Outcome Measures

Primary Outcomes (1)

• overall response rate (ORR).

  Response rate will be evaluated according to the IMWG criteria, after six 28 days cycles of salvage therapy.

  At the end of Cycle 6 of salvage therapy (each cycle is 28 days)

Secondary Outcomes (5)

• best overall response rate (ORR)

  2 years

• Time To Progress (TTP)

  2 years

• Progression free survival (PFS)

  2 years

• Overall survival OS

  2 years

• Quality of Life (QoL)

  2 years

Study Arms (2)

Dexamethasone-free

EXPERIMENTAL

Dexamethasone will be stopped after the first 2 cycles (in both ICARIA and IKEMA schemas). ICARIA shemas : dexamethasone isatuximab pomalidomide IKEMA shemas : dexamethasone isatuximab carfilzomib

Drug: Dexamethasone

Dexamethasone

NO INTERVENTION

Dexamethasone will not be discontinued (in both ICARIA and IKEMA shemas). ICARIA schema : dexamethasone isatuximab pomalidomide IKEMA schema : dexamethasone isatuximab carfilzomib

Interventions

Dexamethasone DRUG

ICARIA schema : 40mg (20mg for ≥75yr) on day 1, 8, 15, 22 of each cycle plus IKEMA schema : 20 mg on day 1-2, day 8-9, day 15-16 and day 22-23 of each cycle For subjects older than 75 years or underweight (BMI \<18.5), the dexamethasone dose may be administered at a total dose of 20 mg weekly. In both schema (ICARIA or IKEMA), dexamethasone will be administrated up to 2 cycle (Arm 1) or until disease progression (Arm2)

Also known as: Neofordex

Dexamethasone-free

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• ICARIA schema: isatuximab, pomalidomide and dexamethasone.
• 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

You may not qualify if:

• Contraindications to investigational medicinal products or auxiliary medicinal product
• Evidence of refractoriness or intolerance to anti-CD38 monoclonal antibodies.
• Previous treatment according to the ICARIA schema with pomalidomide or IKEMA schema with carfilzomib
• Allogenic hematopoietic cell transplant (HCT, regardless of timing).
• Planned to undergo an hematopoietic cell transplant 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
• Lactation
• Participation to another interventional clinical trial

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Service d'hématologie clinique et thérapie cellulaire, Saint-Antoine Hospital

Paris, 75012, France

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Mohamad MOHTY, PU-PH

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mohamad MOHTY, PU-PH

CONTACT

+ 33 1 49 28 26 20; mohamad.mohty@inserm.fr

Florent MALARD, PU-PH

CONTACT

01 49 28 34 39; malardf@yahoo.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2024
• First Posted: August 20, 2024
• Study Start: December 12, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: December 18, 2024

Record last verified: 2024-12

Locations

FR (1)