Multiple MyelomaPhase 3FREEDOMNCT06561854
Study Comparing Therapy for Advanced Relapsed/Refractory Multiple Myeloma With and Without Dexamethasone
A Phase 3 study testing Dexamethasone in people with Multiple Myeloma and Relapse Multiple Myeloma, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma, Relapse Multiple Myeloma
- What is being tested?
- Dexamethasone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 318 participants
- Where
- 1 siteFrance
- Study dates
- 12 Dec 2024to Dec 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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).
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- 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
- Inability to give written informed consent
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Service d'hématologie clinique et thérapie cellulaire, Saint-Antoine Hospital
Paris, 75012
Florent MALARD, PU-PH, 01 49 28 34 39, florent.malard@aphp.fr
Mohamad MOHTY, PU-PH, 01 49 28 26 20, mohamad.mohty@inserm.fr
About this study
Official title: Free Regimen of Dexamethasone as Initial Therapy for Advanced Relapsed/Refractory Multiple Myeloma: an Open-label Randomized, Non-inferiority, Controlled Trial
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.
Read the detailed description
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 are as follow, but 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.
- ICARIA schema:
- dexamethasone: 40mg (20mg for ≥75yr) on day 1, 8, 15, 22 of each cycle plus
- isatuximab: 10mg/kg on day 1, 8, 15, 22 in C1 subsequently on day 1, 15; plus
- pomalidomide: 4mg on days 1-21 of 28-day cycle.
- IKEMA schema:
- dexamethasone: 20 mg on day 1-2, day 8-9, day 15-16 and day 22-23 of each cycle;
- isatuximab: 10 mg/kg on day 1, 8, 15, 22 in C1, then Q2W;
- carfilzomib: 20 mg/m² on day 1-2; 56 mg/m² day 8-9, day, 15-16 in C1; 56 mg/m² on day 1-2, day 8-9, day 15-16 all subsequent cycles.
In the dexamethasone arm (standard of care):
Dexamethasone: will be given on each cycle
In the dexamethasone-free arm (experimental arm):
Dexamethasone: will be only given on cycle 1 and cycle 2 Supportive care: will be administered according to each participating center's usual practice, in both arms The aim of the current protocol is to investigate whether administration of dexamethasone for a very limited period (2 cycles) combined with standard treatment for relapsed/refractory MM is not inferior to the continuous administration of the combination until disease progression. In this study some patients may have a similar OS while receiving a shorter duration of dexamethasone treatment. This study may allow delivery of a shorter duration of dexamethasone for the treatment of relapsed MM.
The foreseeable risks are those of an earlier relapse in patients receiving a short duration of dexamethasone (8 weeks) compared to the situation where they would have received the dexamethasone until disease progression.
- Conditions
- Multiple Myeloma, Relapse Multiple Myeloma
- Being tested
- Dexamethasone
- Keywords
- Multiple myeloma, Relapse, Dexamethasone, Isatuximab, Pomalidomide, Carfilzomib
- Medical subject headings
- Multiple Myeloma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
Also called Neofordex
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)
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
overall response rate (ORR).
Response rate will be evaluated according to the IMWG criteria, after six 28 days cycles of salvage therapy.
Measured: At the end of Cycle 6 of salvage therapy (each cycle is 28 days)
Secondary outcomes (5)
best overall response rate (ORR)
Response rate will be evaluated according to the IMWG criteria, during or after the study treatment at the time of data cutoff. Patients will be followed every 4 weeks (with either a medical visit or only an outpatient blood test) until disease progression and then every 12 weeks until final 2 years.
Measured: 2 years
Time To Progress (TTP)
Time To Progress defined as the duration from the date of randomization to progressive disease, according to the IMWG criteria
Measured: 2 years
Progression free survival (PFS)
Progression free survival is defined as the duration from the date of randomization to either progressive disease, according to the IMWG critera or death, at 2 years after randomization.
Measured: 2 years
Overall survival OS
which is defined as the time between randomization and death due to any cause. Patients, who die, regardless of the cause of death, will be considered to have had an event even if they were lost to follow-up for an extended time
Measured: 2 years
Quality of Life (QoL)
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2024
- Study start12 Dec 2024
- Primary completionDec 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 318 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mohamad MOHTY, PU-PH, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06561854
- Sponsor's protocol ID
- APHP231089
- Other IDs
- 2024-510981-18-00
- Acronym
- FREEDOM
- Status last verified
- Dec 2024
- First submitted
- 7 Aug 2024
- Last updated
- 18 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Free Regimen of Dexamethasone as Initial Therapy for Advanced Relapsed/Refractory Multiple Myeloma: an Open-label Randomized, Non-inferiority, Controlled Trial
- ClinicalTrials.gov ID
- NCT06561854
- Acronym / sponsor ID
- FREEDOM / APHP231089
- Conditions
- Multiple Myeloma, Relapse Multiple Myeloma
- Keywords
- Multiple myeloma, Relapse, Dexamethasone, Isatuximab, Pomalidomide, Carfilzomib
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 318 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 12 Dec 2024 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 20 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 are as follow, but 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.
- ICARIA schema:
- dexamethasone: 40mg (20mg for ≥75yr) on day 1, 8, 15, 22 of each cycle plus
- isatuximab: 10mg/kg on day 1, 8, 15, 22 in C1 subsequently on day 1, 15; plus
- pomalidomide: 4mg on days 1-21 of 28-day cycle.
- IKEMA schema:
- dexamethasone: 20 mg on day 1-2, day 8-9, day 15-16 and day 22-23 of each cycle;
- isatuximab: 10 mg/kg on day 1, 8, 15, 22 in C1, then Q2W;
- carfilzomib: 20 mg/m² on day 1-2; 56 mg/m² day 8-9, day, 15-16 in C1; 56 mg/m² on day 1-2, day 8-9, day 15-16 all subsequent cycles.
In the dexamethasone arm (standard of care):
Dexamethasone: will be given on each cycle
In the dexamethasone-free arm (experimental arm):
Dexamethasone: will be only given on cycle 1 and cycle 2 Supportive care: will be administered according to each participating center's usual practice, in both arms The aim of the current protocol is to investigate whether administration of dexamethasone for a very limited period (2 cycles) combined with standard treatment for relapsed/refractory MM is not inferior to the continuous administration of the combination until disease progression. In this study some patients may have a similar OS while receiving a shorter duration of dexamethasone treatment. This study may allow delivery of a shorter duration of dexamethasone for the treatment of relapsed MM.
The foreseeable risks are those of an earlier relapse in patients receiving a short duration of dexamethasone (8 weeks) compared to the situation where they would have received the dexamethasone until disease progression.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dexamethasone-free | Experimental | Drug: DexamethasoneDexamethasone will be stopped after the first 2 cycles (in both ICARIA and IKEMA schemas). ICARIA shemas : dexamethasone isatuximab pomalidomide IKEMA shemas : dexamethasone isatuximab carfilzomib |
| Dexamethasone | No intervention | –Dexamethasone will not be discontinued (in both ICARIA and IKEMA shemas). ICARIA schema : dexamethasone isatuximab pomalidomide IKEMA schema : dexamethasone isatuximab carfilzomib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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)
- Subject must have achieved a response (PR or better) to the prior regimen.
- ECOG Performance Status score of 0, 1, or 2.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexamethasoneAlso: NeofordexICARIA 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) | Drug | Dexamethasone-free |
Primary outcome
overall response rate (ORR).
Time frame: At the end of Cycle 6 of salvage therapy (each cycle is 28 days)
Response rate will be evaluated according to the IMWG criteria, after six 28 days cycles of salvage therapy.
5 secondary outcomes
best overall response rate (ORR)
Time frame: 2 years
Time To Progress (TTP)
Time frame: 2 years
Progression free survival (PFS)
Time frame: 2 years
Overall survival OS
Time frame: 2 years
Quality of Life (QoL)
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mohamad MOHTY, PU-PH principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dexamethasone in people with Multiple Myeloma and Relapse Multiple Myeloma, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mohamad MOHTY, PU-PH (+ 33 1 49 28 26 20, mohamad.mohty@inserm.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
overall response rate (ORR). (time frame: At the end of Cycle 6 of salvage therapy (each cycle is 28 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2024.