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History of Changes for Study: NCT03180736
Compare Progression Free Survival Btw Daratumumab/Pomalidomide/Dexamethasone vs Pomalidomide/Dexamethasone (EMN14)
Latest version (submitted February 22, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 June 7, 2017 None (earliest Version on record)
2 June 28, 2017 Recruitment Status, Study Status, Contacts/Locations and Oversight
3 December 6, 2017 Study Status, Arms and Interventions, Study Identification, Eligibility, Outcome Measures and Study Description
4 January 8, 2018 Study Status and Contacts/Locations
5 April 12, 2018 Contacts/Locations and Study Status
6 July 16, 2019 Recruitment Status, Contacts/Locations, Study Status and Study Design
7 July 21, 2020 Study Status
8 February 19, 2021 Study Status
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Results Submission Events
9 February 22, 2022 Study Status, Outcome Measures, Document Section and Results
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Study NCT03180736
Submitted Date:  June 7, 2017 (v1)

Open or close this module Study Identification
Unique Protocol ID: EMN14/54767414MMY3013
Brief Title: Compare Progression Free Survival Btw Daratumumab/Pomalidomide/Dexamethasone vs Pomalidomide/Dexamethasone (EMN14)
Official Title: Phase 3 Study Comparing Pomalidomide and Dexamethasone w/Without Daratumumab in Subjects With Relapsed or Refractory MM Who Received at Least One Prior Line of Therapy With Both Lenalidomide and a Proteasome Inhibitor.
Secondary IDs:
Open or close this module Study Status
Record Verification: June 2017
Overall Status: Not yet recruiting
Study Start: June 9, 2017
Primary Completion: June 1, 2021 [Anticipated]
Study Completion: July 1, 2023 [Anticipated]
First Submitted: May 30, 2017
First Submitted that
Met QC Criteria:
June 7, 2017
First Posted: June 8, 2017 [Actual]
Last Update Submitted that
Met QC Criteria:
June 7, 2017
Last Update Posted: June 8, 2017 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: European Myeloma Network
Responsible Party: Sponsor
Collaborators: Janssen Research & Development, LLC
Open or close this module Oversight
U.S. FDA-regulated Drug: No
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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.
Detailed Description: This is a multicenter, Phase 3, randomized, open-label study comparing daratumumab, pomalidomide and low-dose dexamethasone (DaraPomDex) with pomalidomide and low-dose dexamethasone (PomDex) in subjects with relapsed or refractory Multiple Myeloma who have received at least 1 prior treatment regimen with both lenalidomide and a proteasome inhibitor and have demonstrated disease progression. Subjects will be randomized in a 1:1 ratio to receive either DaraPomDex or PomDex. Subjects will receive treatment until disease progression or unacceptable toxicity. Drug administration and follow-up visits will occur more frequently for early cycles (e.g., weekly or bi-weekly). Disease evaluations will occur every cycle and consist mainly of measurements of myeloma proteins. Subject safety will be assessed throughout the study. The primary endpoint will be progression-free survival (PFS). Study end is anticipated at approximately 5 years after the last subject is randomized.
Open or close this module Conditions
Conditions: Multiple Myeloma
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Number of Arms: 2
Masking: Single (Participant)
Allocation: Randomized
Enrollment: 302 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Daratumumab+Pomalidomide+Dexamethasone
Daratumumab at a dose of 16 mg/kg administered as an IV infusion 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
Daratumumab at a dose of 16 mg/kg administered as an IV infusion at weekly intervals (QW) for 8 weeks, then every 2 weeks (Q2W) for an additional 16 weeks, then every 4 weeks (Q4W) thereafter
Drug: Pomalidomide
Pomalidomide will be administered at full dose of 4 mg orally (PO) on Days 1 through 21 of each 28-day cycle.
Drug: Dexamethasone
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.
Active Comparator: Pomalidomide + Dexamethasone
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
Pomalidomide will be administered at full dose of 4 mg orally (PO) on Days 1 through 21 of each 28-day cycle.
Drug: Dexamethasone
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.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Comparison of Progression Free Survival between treatment arms
[ Time Frame: Assessed monthly from randomization until disease progression (PD) or death whichever occurs first (approximately up to 3 years)] ]

Comparison of Progression Free Survival between treatment arms (Daratumumab /Pomalidomide /Dexamethasone vs Pomalidomide / Dexamethasone)[ Time Frame: Assessed monthly from randomization until disease progression (PD) or death whichever occurs first (approximately up to 3 years)] Progression free survival is defined as the time, in months, from randomization to the date of the first documented PD or death due to any cause, whichever comes first. PD will be 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.
Secondary Outcome Measures:
1. Overall response rate
[ Time Frame: Assessed monthly from Randomization until PD, (approximately up to 3 years)] ]

Overall response rate is defined as the proportion of randomized subjects who achieve a best response of PR or better using modified IMWG criteria as their best overall response.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  1. Males and females at least 18 years of age.
  2. Voluntary written informed consent before performance of any study-related procedure.
  3. 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.
  4. 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) to prior therapy.
  5. Subjects must have documented evidence of PD as defined by the modified IMWG criteria on or after the last regimen.
  6. 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).
  7. Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2.
  8. Willingness and ability to participate in study procedures.
  9. For subjects experiencing toxicities resulting from previous therapy, the toxicities must be resolved or stabilized to ≤Grade 1.
  10. Any of the following laboratory test results during Screening:
    1. Absolute neutrophil count ≥1.0 × 109/L;
    2. Hemoglobin level ≥7.5 g/dL (≥5 mmol/L);
    3. Platelet count ≥75 × 109/L in subjects in whom <50% of bone marrow nucleated cells are plasma cells and platelet count ≥50 x 109/L in subjects in whom ≥50% of bone marrow nucleated cells are plasma cells;
    4. Alanine aminotransferase (ALT) level ≤2.5 times the upper limit of normal (ULN);
    5. Aspartate aminotransferase (AST) level ≤2.5 x ULN;
    6. Total bilirubin level ≤1.5 x ULN, (except for Gilbert Syndrome: direct bilirubin ≤1.5 × ULN);
    7. Creatinine clearance ≥30 mL/min
    8. Serum calcium corrected for albumin ≤14.0 mg/dL (≤3.5 mmol/L), or free ionized calcium ≤ 6.5 mg/dL (≤1.6 mmol/L).
  11. Reproductive Status
    1. Women of childbearing potential (WOCBP) must have 2 negative serum or urine pregnancy tests, one 10-14 days prior to start of study treatment and one 24 hours prior to the start of study treatment. Females are not of reproductive potential if they have been in natural menopause for at least 24 consecutive months, or have had a hysterectomy and/or bilateral oophorectomy.
    2. Women must not be breastfeeding.
    3. WOCBP must agree to follow instructions for methods of contraception for 4 weeks before the start of study treatment, for the duration of study treatment, and for 3 months after cessation of daratumumab or 4 weeks after cessation of pomalidomide, whichever is longer.
    4. Males who are sexually active must always use a latex or synthetic condom during any sexual contact with females of reproductive potential, even if they have undergone a successful vasectomy. They must also agree to follow instructions for methods of contraception for 4 weeks before the start of study treatment, for the duration of study treatment, and for a total of 3 months post-treatment completion.
    5. Male subjects must not donate sperm for up to 90 days post-treatment completion.
    6. Female subject must not donate eggs for up to 90 days post-treatment completion.
    7. Azoospermic males and WOCBP who are not heterosexually active are exempt from contraceptive requirements. However, WOCBP will still undergo pregnancy testing as described in this section.

Highly effective methods of contraception have a failure rate of < 1% when used consistently and correctly. Subjects must agree to the use of 2 methods of contraception, with 1 method being highly effective and the other method being additionally effective.

Exclusion Criteria:

  1. Previous therapy with any anti-CD38 monoclonal antibody.
  2. Previous exposure to pomalidomide.
  3. 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).
  4. Previous allogenic stem cell transplant; or autologous stem cell transplantation (ASCT) within 12 weeks before C1D1.
  5. 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).
  6. Clinical signs of meningeal involvement of MM.
  7. 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.
  8. Clinically significant cardiac disease, including:
    1. Myocardial infarction within 6 months, or unstable or uncontrolled condition (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV).
    2. Cardiac arrhythmia (Common Terminology Criteria for Adverse Events [CTCAE] Grade 3 or higher) or clinically significant electrocardiogram (ECG) abnormalities.
    3. Electrocardiogram showing a baseline QT interval as corrected QTc >470 msec.
  9. Known active hepatitis A, B, or C.
  10. Known HIV infection.
  11. Gastrointestinal disease that may significantly alter the absorption of pomalidomide.
  12. 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.
  13. Any concurrent medical or psychiatric condition or disease (eg, active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with the study procedures or results or that, in the opinion of the investigator, would constitute a hazard for participating in this study.
  14. Ongoing ≥ Grade 2 peripheral neuropathy.
  15. Subject had ≥Grade 3 rash during prior therapy.
  16. Subject has had major surgery within 2 weeks before randomization, or has not fully recovered from an earlier surgery, or has surgery planned during the time the subject is expected to participate in the study or within 2 weeks after the last dose of study drug administration. Note: subjects with planned surgical procedures to be conducted under local anesthesia may participate. Kyphoplasty or vertebroplasty are not considered major surgery.
  17. Pregnant or nursing women.
Open or close this module Contacts/Locations
Central Contact Person: Pieter Sonneveld, Prof
Telephone: +31.10.7033123
Email: p.sonneveld@erasmusmc.nl
Central Contact Backup: Sarah Lonergan
Telephone: 31 107034546
Email: S.lonergan@erasmusmc.nl
Study Officials: Evangelos Terpos, Prof
Principal Investigator
Department of Clinical Therapeutics, University of Athens, School of Medicine, Athens, Greece
Locations:
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Links:
Available IPD/Information:

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