Comparison of Pom and Dex in Subjects With RRMM Previously Treated With Len and a PI Dara/Pom/Dex vs Pom/Dex

NCT03180736 | Completed Phase 3 Results DMC

• 1 other identifier: EMN14/54767414MMY3013
• Study Type: interventional
• Target: 304
• Locations: 10 countries
• Sites: 40

Brief Summary

The purpose of this study is to evaluate the effects of the addition of daratumumab to pomalidomide and dexamethasone in terms of progression-free survival in subjects with relapsed or refractory Multiple Myeloma.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Comparison of Progression Free Survival Between Treatment Arms (Daratumumab /Pomalidomide /Dexamethasone vs Pomalidomide / Dexamethasone)

  Progression Free Survival (PFS) is defined as the time, in months, from randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever comes first. PFS2 is defined as the time, in months, from randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever comes first, after the next line of therapy. PD is assessed by the investigator based on the analysis of serum and urine protein electrophoresis (sPEP and uPEP), serum and urine immunofixation (sIFE and uIFE), serum free light chain protein (sFLC),corrected serum calcium assessment, imaging and bone marrow assessments as per modified IMWG guidelines.

  PFS is assessed monthly from randomization until PD or death, whichever occurs first (approximately up to 3 years). PFS2 is assessed monthly from randomization until PD or death, whichever occurs first (approximately up to 5 years).

Secondary Outcomes (8)

• Overall Response Rate

  Approximately up to 3 years (assessed monthly from randomization until PD).

• Depth of Response

  MRD is assessed at the time of suspected CR/sCR and 6, 12, 18, 24, and every 12 months (yearly assessments ±3 months) post CR/sCR in subjects who maintain CR. or sCR, until PD.

• Duration of Response

  From informed consent until 30 days after last study treatment, assessed up to approximately 3 years.

• Time to Next Therapy

  From randomization until the date to next anti-neoplastic therapy or death from any cause, whichever comes first (approximately up to 3 years)

• Overall Survival

  From randomization until death from any cause (up to 5 years)

Study Arms (2)

Daratumumab+Pomalidomide+Dexamethasone

EXPERIMENTAL

Daratumumab at a dose of 16 mg/kg administered as an IV infusion (Dara IV) or 1800 mg subcutaneously (Dara SC) at weekly intervals (QW) for 8 weeks, then every 2 weeks (Q2W) for an additional 16 weeks, then every 4 weeks (Q4W) thereafter. Pomalidomide 4 mg orally (PO) on Days 1 through 21 of each 28-day cycle Dexamethasone 40 mg (20 mg for patients ≥75 years of age) orally, once daily on Days 1, 8, 15, and 22 of each 28-day treatment cycle

Drug: Daratumumab; Drug: Pomalidomide; Drug: Dexamethasone

Pomalidomide + Dexamethasone

ACTIVE COMPARATOR

Pomalidomide 4 mg orally (PO) on Days 1 through 21 of each 28-day cycle Dexamethasone 40 mg (20 mg for patients ≥75 years of age) orally, once daily on Days 1, 8, 15, and 22 of each 28-day treatment cycle

Drug: Pomalidomide; Drug: Dexamethasone

Interventions

Daratumumab DRUG

Daratumumab will be given at a dose of 16 mg/kg administered as an IV infusion (Dara IV) or 1800 mg subcutaneously (Dara SC) at weekly intervals (QW) for 8 weeks, then every 2 weeks (Q2W) for an additional 16 weeks, then every 4 weeks (Q4W) thereafter. Subjects will receive pre-infusion medications before infusions to mitigate potential IRRs.

Also known as: Dara

Daratumumab+Pomalidomide+Dexamethasone

Pomalidomide DRUG

Pomalidomide will be administered at full dose of 4 mg orally (PO) on Days 1 through 21 of each 28-day cycle.

Also known as: Pom

Daratumumab+Pomalidomide+Dexamethasone; Pomalidomide + Dexamethasone

Dexamethasone DRUG

Dexamethasone will be administered at a dose of 40 mg (20 mg for patients ≥75 years of age) orally, once daily on Days 1, 8, 15, and 22 of each 28-day treatment cycle.

Also known as: Dex

Daratumumab+Pomalidomide+Dexamethasone; Pomalidomide + Dexamethasone

Eligibility Criteria

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

You may qualify if:

• Males and females at least 18 years of age.
• Voluntary written informed consent before performance of any study-related procedure.
• Subject must have measurable disease of MM as defined by the criteria below:
• IgG multiple myeloma: Serum M protein level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours, or
• IgA, IgD, IgE, IgM multiple myeloma: Serum M-protein level ≥0.5 g/dL or urine M-protein level ≥200 mg/24 hours; or
• Light chain multiple myeloma, for subjects without measurable disease in the serum or urine: Serum immunoglobulin free light chain (FLC) ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio.
• Subjects must have received prior antimyeloma treatment. The prior treatment must have included both a PI- and lenalidomide-containing regimens. The subject must have had a response (ie, PR or better based on the investigator's determination of response as defined by the modified IMWG criteria) to prior therapy.
• Subjects must have documented evidence of PD based on the investigator's determination of response as defined by the modified IMWG criteria on or after the last regimen.
• Subjects who received only 1 line of prior treatment must have demonstrated PD on or within 60 days of completion of the lenalidomide containing regimen (ie, lenalidomide refractory).
• Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2.
• Willingness and ability to participate in study procedures.
• For subjects experiencing toxicities resulting from previous therapy, the toxicities must be resolved or stabilized to ≤Grade 1.
• Any of the following laboratory test results during Screening:
• Absolute neutrophil count ≥1.0 × 109/L;
• Hemoglobin level ≥7.5 g/dL (≥4.65 mmol/L); (transfusions are not permitted to reach this level);

You may not qualify if:

• Previous therapy with any anti-CD38 monoclonal antibody.
• Previous exposure to pomalidomide.
• Subject has received antimyeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of randomization. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum of 4 days) for palliative treatment before Cycle 1, Day 1 (C1D1).
• Previous allogenic stem cell transplant; or autologous stem cell transplantation (ASCT) within 12 weeks before C1D1.
• 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 breast, or other non-invasive lesion that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years).
• Clinical signs of meningeal involvement of MM.
• Chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) \<50% of predicted normal. Note that FEV1 testing is required for subjects suspected of having COPD and subjects must be excluded if FEV1 \<50% of predicted normal.
• Clinically significant cardiac disease, including:
• Myocardial infarction within 6 months, before C1D1 or unstable or uncontrolled condition (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV).
• Cardiac arrhythmia (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade 3 or higher) or clinically significant electrocardiogram (ECG) abnormalities.
• Electrocardiogram showing a baseline QT interval as corrected QTc \>470 msec.
• Known active hepatitis A, B, or C.
• Known HIV infection.
• Gastrointestinal disease that may significantly alter the absorption of pomalidomide.
• 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.

Sponsors & Collaborators

• Janssen Research & Development, LLC: collaborator
• Stichting European Myeloma Network: lead

Study Sites (40)

Antwerpen

Antwerp, Belgium

Location

Brussel

Brussels, Belgium

Location

UZ Gent

Ghent, Belgium

Location

Yvoir

Yvoir, Belgium

Location

Brno

Brno, Czechia

Location

Ostrava

Ostrava, Czechia

Location

Praha 2

Prague, Czechia

Location

Odense

Odense, Denmark

Location

Vejle

Vejle, Denmark

Location

Freiburg

Freiburg im Breisgau, Germany

Location

Hamburg

Hamburg, Germany

Location

Heidelberg

Heidelberg, Germany

Location

Kiel

Kiel, Germany

Location

Schwerin

Schwerin, Germany

Location

Tübingen

Tübingen, Germany

Location

Würzburg

Würzburg, Germany

Location

General Hospital of Athens "Evangelismos"

Athens, Greece

Location

University of Athens School of Medicine

Athens, Greece

Location

General University Hospital of Patras

Pátrai, Greece

Location

Anticancer Hospital of Thessaloniki "Theageneio"

Thessaloniki, Greece

Location

Ancona

Ancona, Italy

Location

Bologna

Bologna, Italy

Location

Brescia

Brescia, Italy

Location

Milano

Milan, Italy

Location

Roma

Roma, Italy

Location

Torino

Torino, Italy

Location

VU MC

Amsterdam, Netherlands

Location

Erasmus MC

Rotterdam, Netherlands

Location

Belgrade

Belgrade, Serbia

Location

Badalona

Badalona, Spain

Location

Barcelona

Barcelona, Spain

Location

Hospital Quirón Salud Madrid

Madrid, Spain

Location

Hospital Universitario de la Princesa

Madrid, Spain

Location

Salamanca University Hospital

Salamanca, Spain

Location

Doctor Peset University Hospital Medical Centre

Valencia, Spain

Location

Cebeci

Cebeli, Turkey (Türkiye)

Location

Capa

Çapa, Turkey (Türkiye)

Location

Gaziantep

Gaziantep, Turkey (Türkiye)

Location

Izmir

Izmir, Turkey (Türkiye)

Location

Kayseri

Kayseri, Turkey (Türkiye)

Location

Related Publications (3)

• Dimopoulos MA, Terpos E, Boccadoro M, Delimpasi S, Beksac M, Katodritou E, Moreau P, Baldini L, Symeonidis A, Bila J, Oriol A, Mateos MV, Einsele H, Orfanidis I, Kampfenkel T, Liu W, Wang J, Kosh M, Tran N, Carson R, Sonneveld P. Subcutaneous daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma (APOLLO): extended follow up of an open-label, randomised, multicentre, phase 3 trial. Lancet Haematol. 2023 Oct;10(10):e813-e824. doi: 10.1016/S2352-3026(23)00218-1.

  PMID: 37793772 DERIVED

• He J, Berringer H, Heeg B, Ruan H, Kampfenkel T, Dwarakanathan HR, Johnston S, Mendes J, Lam A, Bathija S, Mackay EK. Indirect Treatment Comparison of Daratumumab, Pomalidomide, and Dexamethasone Versus Standard of Care in Patients with Difficult-to-Treat Relapsed/Refractory Multiple Myeloma. Adv Ther. 2022 Sep;39(9):4230-4249. doi: 10.1007/s12325-022-02226-x. Epub 2022 Jul 22.

  PMID: 35876974 DERIVED

• Dimopoulos MA, Terpos E, Boccadoro M, Delimpasi S, Beksac M, Katodritou E, Moreau P, Baldini L, Symeonidis A, Bila J, Oriol A, Mateos MV, Einsele H, Orfanidis I, Ahmadi T, Ukropec J, Kampfenkel T, Schecter JM, Qiu Y, Amin H, Vermeulen J, Carson R, Sonneveld P; APOLLO Trial Investigators. Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Jun;22(6):801-812. doi: 10.1016/S1470-2045(21)00128-5.

  PMID: 34087126 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; darlin protein, Dictyostelium; 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

Results Point of Contact

• Title: Sarah Lonergan, Trial lead
• Organization: EMN

sarah.lonergan@emn.life

+44 7767565020

Study Officials

• Evangelos Terpos, Prof

  Department of Clinical Therapeutics, University of Athens, School of Medicine, Athens, Greece

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Masking: Open Label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment

Study Record Dates

• First Submitted: May 30, 2017
• First Posted: June 8, 2017
• Study Start: June 14, 2017
• Primary Completion: July 21, 2020
• Study Completion: November 30, 2024
• Last Updated: December 19, 2025
• Results First Posted: May 11, 2022

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

ES (6); IT (6); NL (2); GR (4); BE (4); CZ (3); DK (2); SE (1); TU (5); DE (7)