NCT04124497

A Trial for Relapsed and Relapsed/Refractory Multiple Myeloma Patients

Daratumumab, Pomalidomide and Dexamethasone for Del(17p) Positive Relapsed and Relapsed/Refractory Multiple Myeloma Patients [DEDALO]

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Sponsor: Fondazione EMN Italy Onlus · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Multiple myeloma (MM) with chromosome 17 deletion (del(17p) represents one of the most dangerous genetic variant of this disease, since it is associated with a high level of genomic instability. Del(17p) is present in approximately 10% of patients at diagnosis, and its frequency increases with disease evolution. The adverse prognosis of del(17p) has been observed in patients treated with conventional chemotherapy and new drugs. Only very few studies have suggested an advantage in treating del(17p) MM patients with specific therapies. In particular, several recent trials combining lenalidomide plus dexamethasone with a new agent, suggested that high risk cytogenetics patients may benefit from newest generation drugs. Yet, in all studies, outcome of patients with high risk genetic features have been derived from subgroup analyses, with all the limitations of this approach. To date no trial has been designed with the specific aim to test genotype-adapted therapies. The objective of the present study is to evaluate the combination of daratumumab-pomalidomide-dexamethasone (DPd) in relapsed or relapsed/refractory MM patients harboring del(17p). Treatment of relapsed or relapsed/refractory MM patients harbouring del(17p) is a relevant unmet medical need. A clinical trial designed to test a tailored treatment for this patient population would be a major improvement. In this perspective the combination DPd seems attractive since: * both daratumumab and pomalidomide are therapies not interfering with DNA replication, thus not increasing the intrinsic genomic instability of del(17p) plasma cells. * the POLLUX study has shown that daratumumab in combination with lenalidomide is highly effective in relapsed and relapsed/refractory MM patients.10 * the IFM 2010-02 trial has suggested that pomalidomide may be effective in del(17p) patients. * the DPd combination has been successfully tested in MM patients with advanced disease.

Detailed description

Patients will undergo screening for protocol eligibility within 28 days (4 weeks) of enrolment. After providing written informed consent to participate in the study, patients will be evaluated for study eligibility. It is to note that patients can be enrolled based on the presence of del(17p), as per center evaluation. However, the presence of del(17p) should be confirmed by the central laboratory (University of Torino laboratory), which will perform the test in 5 working days. After registration, subjects who meet all the inclusion criteria will be treated according to the protocol, only after the presence of del(17p) has been confirmed by the central laboratory. Treatment period includes administration of 28-day cycles of treatment with DPd until any sign of progression or intolerance. The response will be assessed after each cycle. The LTFU period will start after development of confirmed progressive disease (PD) or treatment interruption due to toxicity. All patients are to be followed for survival during the LTFU period every 3 months via telephone or office visit.

Conditions

• Multiple Myeloma
• Deletion 17P Syndrome

Interventions

Type	Name	Description
DRUG	Daratumumab	* Daratumumab 16 mg/kg intravenously at following schedule: * cycle 1 and 2: days 1, 8, 15, and 22 * cycle 3 through 6: days 1, and 15 * from cycle 7 until disease progression: day 1.
DRUG	Pomalidomide	4 mg once daily on days 1-21
DRUG	Dexamethasone	Oral or intravenous dexamethasone 40 mg/day (≤ 75 years old) or 20 mg/ day (\>75 years old) on days 1, 8, 15 and 22

Timeline

• Start date: 2019-07-01
• Primary completion: 2027-07-01
• Completion: 2027-07-01
• First posted: 2019-10-11
• Last updated: 2025-08-08

Locations

15 sites across 1 country: Italy