A Trial for Relapsed and Relapsed/Refractory Multiple Myeloma Patients

NCT04124497 | Active Not Recruiting Phase 2

• 1 other identifier: DEDALO
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 15

Brief 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.

Conditions

Multiple Myeloma; Deletion 17P Syndrome

Keywords

Multiple Myeloma; Monoclonal antibody; Immunomodulating agents

Outcome Measures

Primary Outcomes (1)

• Minimal residual disease (MRD)

  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.

  5 years

Secondary Outcomes (8)

• Progression-free survival (PFS)

  5 years

• Overall response rate (ORR)

  5 years

• Progression-free survival 2 (PFS2)

  5 years

• Duration of response (DOR)

  5 years

• Overall survival (OS)

  5 years

Study Arms (1)

Daratumumab Pomalidomide dexamethasone

EXPERIMENTAL

Therapy consists in cycles of the DPd combination as follows: * Pomalidomide 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; * 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: Daratumumab; Drug: Pomalidomide; Drug: Dexamethasone

Interventions

Daratumumab DRUG

* 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.

Also known as: Darzalex

Daratumumab Pomalidomide dexamethasone

Pomalidomide DRUG

4 mg once daily on days 1-21

Also known as: Imnovid

Daratumumab Pomalidomide dexamethasone

Dexamethasone DRUG

Oral or intravenous dexamethasone 40 mg/day (≤ 75 years old) or 20 mg/ day (\>75 years old) on days 1, 8, 15 and 22

Daratumumab Pomalidomide dexamethasone

Eligibility Criteria

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

You may qualify if:

• Patient has given voluntary written informed consent
• Subject must be at least 18 years of age.
• Subject must have documented MM.
• Subject must have del(17p) observed by FISH in at least 10% of bone marrow plasma cells at any time of MM history.
• Subject must have serum monoclonal paraprotein (M-protein) level \>=0.5 g/dL or urine M-protein, level \>=200 mg/24 hours, or light chain MM, or serum immunoglobulin free light chain ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio.
• Subject must have received at least 1 and no more than 3 prior lines of therapy for MM.
• Subject must have received at least 2 consecutive cycles of lenalidomide in a previous line of therapy.
• Subject must have achieved a response (PR or better) to at least one prior regimen.
• Subjects must have either refractory or relapsed and refractory disease defined as documented disease progression during or within 60 days of completing their last myeloma therapy.
• Subject must have an ECOG Performance Status score of 0, 1, or 2.
• Subject must have the following laboratory values:
• Platelet count \>=50 x 109/L (≥30 x 109 /L if myeloma involvement in the bone marrow is \> 50%) within 14 days prior to drug administration).
• Absolute neutrophil count (ANC) \>= 1 x 109/L without the use of growth factors.
• Corrected serum calcium \<=14 mg/dL (3.5 mmol/L)
• Alanine transaminase (ALT): \<= 3 x the upper limit normal (ULN).

You may not qualify if:

• Subject has received daratumumab or other anti-CD38 monoclonal antibody previously.
• Subject's disease shows evidence of refractoriness or intolerance to pomalidomide. If previously treated with a pomalidomide-containing regimen, the subject is excluded if he or she:
• Discontinued due to any adverse event related to prior pomalidomide treatment, or
• If, at any time point, the subject was refractory to any dose of pomalidomide.
• Refractory to pomalidomide is defined either:
• Subjects whose disease progresses within 60 days of pomalidomide; or
• Subjects whose disease is nonresponsive while on lenalidomide. Nonresponsive disease is defined as either failure to achieve at least an MR or development of PD while on pomalidomide.
• Subject has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of randomization.
• Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant less than 12 months prior to initiation of study treatment and who have not discontinued immunosuppressive treatment for at least 16 weeks prior to initiation of study treatment and are currently dependent on such treatment.
• Subjects unable or unwilling to undergo antithrombotic prophylactic treatment.
• Subject has a history of malignancy (other than multiple myeloma) within 3 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, in agreement with the medical monitor, is considered cured with minimal risk of recurrence within 3 years).
• Subject has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume in 1 second (FEV1) \<60% of predicted normal), asthma, or a history of asthma within the last 2 years. Subjects with known or suspected COPD must have a forced expiratory volume (FEV) test during Screening.
• Subject is known to be seropositive for human immunodeficiency virus (HIV) or hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\] or antibodies to hepatitis B surface and core antigens \[anti-HBs and anti-HBc, respectively\]) or hepatitis C (anti-HCV antibody positive or HCV-RNA quantitation positive).
• 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.
• Subject has clinically significant cardiac disease, including:

Sponsors & Collaborators

• Fondazione EMN Italy Onlus: lead

Study Sites (15)

AOU Ospedali Riuniti Umberto I

Ancona, Italy

Location

Policlinico-Università degli Studi

Bari, Italy

Location

Ospedali Riuniti

Bergamo, Italy

Location

Policlinico S. Orsola

Bologna, Italy

Location

A.O. Spedali Civili di Brescia

Brescia, Italy

Location

AOU Policlinico Vittorio Emanuele

Catania, Italy

Location

Ospedale Niguarda Cà Grande

Milan, Italy

Location

Ospedale Maggiore

Novara, Italy

Location

Dipart. Di Medicina Interna e Scienze Biomediche

Parma, Italy

Location

Ospedale Oncologico Regionale

Rionero in Vulture, Italy

Location

Policlinico Umberto I - Università La Sapienza

Roma, Italy

Location

Istituto Clinico Humanitas

Rozzano, Italy

Location

A.O. Santa Maria

Terni, Italy

Location

AOU Città della Salute e della Scienza di Torino - Presidio Molinette

Torino, Italy

Location

Policlinico Universitario di Udine

Udine, Italy

Location

MeSH Terms

Conditions

Multiple Myeloma; Chromosome 17 deletion

Interventions

daratumumab; pomalidomide; 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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Vittorio Montefusco

  Ospedale San Carlo Borromeo - Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2019
• First Posted: October 11, 2019
• Study Start: July 1, 2019
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: August 8, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (15)