Informations générales (source: ClinicalTrials.gov)

NCT03836014 Active, sans recrutement
A Multi-center Phase III Randomized Study Comparing Continuous Versus Fixed Duration Therapy With Daratumumab, Lenalidomide, and Dexamethasone for Relapsed Multiple Myeloma (CONFIRM)
Interventional
  • Myélome multiple
  • Récidive
  • Tumeurs à plasmocytes
Phase 3
Assistance Publique - Hôpitaux de Paris (Voir sur ClinicalTrials)
juillet 2019
juillet 2026
07 décembre 2024
The incorporation of proteasome inhibitors and immunomodulatory drugs into the standard of care has improved the outcome for patients with multiple myeloma (MM) over the past 10 years. However, most patients (>85%) still eventually relapse around 3-4 years after diagnosis, and ultimately die of their disease, despite salvage therapies. Relapse can occur even when complete remission is achieved after first-line therapy. Currently, daratumumab (Dara) is approved by the american FDA and EMA in combination with lenalidomide (Len) and dexamethasone (Dex) or bortezomib and Dex for the treatment of MM patients who have received at least one prior therapy. Therefore, the Dara-Len-Dex combination is likely to become the most widely used standard of care regimen for MM at the time of first relapse. However, although approval of the latter combination is meant for until disease progression (PD) ("continuous therapy") (CT), the actual optimal duration of relapse treatment is still unknown. Of note, many experts advocate that a "fixed duration" of therapy should be favored, especially if one can show that CT does not translate into a significant overall survival (OS) benefit. As a matter of fact, given the extremely high cost of such novel agents (>100 KEuros/year/patient), the pharmacoeconomic consequences of a "continuous" versus "fixed" duration therapy are also of utmost importance. Based on this background, the investigator propose to conduct a non-inferiority phase III randomized, multicenter, open label trial for treatment of MM at first relapse, comparing the Dara-Len-Dex combination administered continuously until PD, versus a fixed duration of 24 months. The choice of this duration is justified by the currently available evidence with respect to achievement of a plateau in terms of deep disease response, patients' compliance, and physicians' preference according to different surveys. The primary objective of this study is to estimate the OS rate at 4 years after diagnosis of relapse and initiation of salvage therapy. The primary endpoint is OS at 4 years after randomization. The analysis will be performed on both per-protocol and intent-to-treat sets of patients.
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Etablissements

Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données
AP-HP - Hôpital Avicenne MOHTY Mohamad Active, sans recrutement 18/04/2025 07:56:10  Contacter
AP-HP - Hôpital Henri Mondor-Albert Chenevier MOHTY Mohamad Active, sans recrutement 18/04/2025 07:56:10  Contacter
AP-HP - Hôpital Lariboisiere-Fernand Widal MOHTY Mohamad Active, sans recrutement 18/04/2025 07:56:10  Contacter
AP-HP - Hôpital Necker-Enfants Malades MOHTY Mohamad Active, sans recrutement 18/04/2025 07:56:10  Contacter
AP-HP - Hôpital Saint Antoine MOHTY Mohamad Active, sans recrutement 18/04/2025 07:56:10  Contacter

Critères

Tous
Inclusion Criteria:

1. Adult patients (≥ 18 years old)

2. Documented MM in relapse according to standard criteria and requiring initiation of
a first line salvage therapy.

3. Subject must have received one prior line of therapy for MM.

4. Subject must have achieved a response (PR or better) to the prior regimen.

5. Subject must have an ECOG Performance Status score of 0, 1, or 2.

6. For subjects experiencing toxicities resulting from previous therapy (including
peripheral neuropathy), the toxicities must have been resolved or stabilized.

7. Signed informed consent

8. Affiliation to a social security system or equivalent (recipient or assign)

9. Effective method of contraception for the duration of treatment and 3 months after
the last dose for women of childbearing age and men with a partner of childbearing
age:

- Progestin-only pill associated with inhibition of ovulation

- Hormonal methods of contraception, including oral contraceptive pills
containing a combination of estrogen + progesterone, vaginal ring, injectables,
implants and intrauterine devices (IUDs)

- non-hormonal IUD

- Bilateral tubal occlusion

- Vasectomized partner with documented azoospermia 90 days after procedure and
who received a medical assessment of surgical success

- Intrauterine hormone release system (IUS)

- Complete Abstinence: Complete abstinence is defined as the complete avoidance
of heterosexual intercourse. Complete abstinence is an acceptable form of
contraception for all study drugs and must be used throughout the duration of
the study and for the duration of time as specified above. It is not necessary
to use any other method of contraception when complete abstinence is elected.
Acceptable alternate methods of highly effective contraception must be
discussed in the event that the subject chooses to forego complete abstinence.


1. Evidence of refractoriness or intolerance to lenalidomide and/or daratumumab (or
another anti CD38 monoclonal antibody). If previously treated with a lenalidomide or
daratumumab-containing regimen, the subject is excluded if he or she:

- Discontinued due to any severe adverse event related to prior lenalidomide
and/or daratumumab (or another anti CD38 monoclonal antibody) treatment, or

- If, at any time point, the subject was refractory to any dose of lenalidomide
and/or daratumumab (or another anti CD38 monoclonal antibody). Refractoriness
to lenalidomide and/or daratumumab (or another anti CD38 monoclonal antibody)
is defined either as:

- Subjects whose disease progressed within 60 days of lenalidomide and/or
daratumumab (or another anti CD38 monoclonal antibody) administration; or

- Subjects whose disease is nonresponsive while on lenalidomide and/or
daratumumab (or another anti CD38 monoclonal antibody). Nonresponsive
disease is defined as either failure to achieve at least a minimal
response or development of progressive disease while on lenalidomide
and/or daratumumab (or another anti CD38 monoclonal antibody).

2. Subject has received an allogenic stem cell transplant (regardless of timing).

3. Subjects planning to undergo a stem cell transplant prior to progression of disease
on this study, ie, these subjects should not be enrolled in order to reduce disease
burden prior to transplant.

4. Subject has a 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).

5. Subject has known MM meningeal involvement.

6. Subject has 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.

7. Subject has any concurrent medical condition or disease (eg, 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 for participating in this
study.

8. Subject has known uncontrolled chronic obstructive pulmonary disease (COPD)

9. Subject has clinically significant cardiac disease.

10. Subject is known to be seropositive for human immunodeficiency virus (HIV),
hepatitis B or hepatitis C.

11. Creatinine clearance ≤30 mL/min (MDRD method) (lenalidomide dose adjustment will be
considered for subjects with creatinine clearance 30-60 mL/min).

12. Hypersensitivity to the active substance or to any of the excipients

13. Pregnancy or lactation women