A Trial for Relapsed and Relapsed/Refractory Multiple Myeloma Patients (DPd)
|ClinicalTrials.gov Identifier: NCT04124497|
Recruitment Status : Active, not recruiting
First Posted : October 11, 2019
Last Update Posted : October 11, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma Deletion 17P Syndrome||Drug: Daratumumab Drug: Pomalidomide Drug: Dexamethasone||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||45 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Daratumumab, Pomalidomide and Dexamethasone for Del(17p) Positive Relapsed and Relapsed/Refractory Multiple Myeloma Patients [DEDALO]|
|Actual Study Start Date :||July 1, 2019|
|Estimated Primary Completion Date :||July 1, 2024|
|Estimated Study Completion Date :||July 1, 2024|
Therapy consists in cycles of the DPd combination as follows:
4 mg once daily on days 1-21
Oral or intravenous dexamethasone 40 mg/day (≤ 75 years old) or 20 mg/ day (>75 years old) on days 1, 8, 15 and 22
- Minimal residual disease (MRD) [ Time Frame: 5 years ]Molecular minimal residual disease (MRD) 10-5 negativity rate assessed by means of next-generation sequencing (ClonoSEQ assay) in patients attaining a complete remission in the first year of treatment.
- Progression-free survival (PFS) [ Time Frame: 5 years ]Number of months from the date of randomization to the date of first observation of PD, or death from any cause as an event.
- Overall response rate (ORR) [ Time Frame: 5 years ]Overall response rate will include complete response (CR), very good partial response (VGPR) and partial response (PR) using the International Response Criteria. Responders are defined as subjects with at least a PR.
- Progression-free survival 2 (PFS2) [ Time Frame: 5 years ]Time from randomization to objective tumor progression on next-line treatment or death from any cause.
- Duration of response (DOR) [ Time Frame: 5 years ]Time between first documentation of response and PD. Responders without disease progression will be censored either at the time of lost to FU, at the time of death due to other cause than PD, or at the end of the study.
- Overall survival (OS) [ Time Frame: 5 years ]Time between randomization and death. Subjects who die will be censored at time of death as an event, regardless cause of death.
- Safety as incidence of toxicities [ Time Frame: 5 years ]Severity of the toxicities will be graded according to the NCI CTC v.5 whenever possible. Laboratory data will be graded according to NCI CTC v.5 severity grade.
- Time to next therapy (TNT) [ Time Frame: 5 years ]Time to next therapy will be measured from the date of randomization to the date of next anti-myeloma therapy. Death due to any cause before starting therapy will be considered an event.
- Percentage of patients with negative MRD and survival indices [ Time Frame: 5 years ]MRD negativity rate and survival might significantly change in particular subgroups of patients, that are defined on prognostic factors [ISS stage, additional cytogenetic abnormalities, previous treatment, presence of del(17p)]. Hence, subgroup analyses will be conducted.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04124497
|Torino, Italy, 10125|