Comparison of Pomalidomide and Dexamethasone With or Without Daratumumab in Subjects With Relapsed or Refractory Multiple Myeloma Previously Treated With Lenalidomide and a Proteasome InhibitorDaratumumab/Pomalidomide/Dexamethasone vs Pomalidomide/Dexamethasone

• Register: ClinicalTrials.gov
• Last refreshed on: 1 March 2021
• Main ID: NCT03180736
• Date of registration: 30/05/2017
• Prospective Registration: Yes
• Primary sponsor: European Myeloma Network
• Public title: Comparison of Pomalidomide and Dexamethasone With or Without Daratumumab in Subjects With Relapsed or Refractory Multiple Myeloma Previously Treated With Lenalidomide and a Proteasome InhibitorDaratumumab/Pomalidomide/Dexamethasone vs Pomalidomide/Dexamethasone EMN14
• Scientific title: A Phase 3 Study Comparing Pomalidomide and Dexamethasone With or Without Daratumumab in Subjects With Relapsed or Refractory Multiple Myeloma Who Have Received at Least One Prior Line of Therapy With Both Lenalidomide and a Proteasome Inhibitor.
• Date of first enrolment: June 12, 2017
• Target sample size: 304
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT03180736
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Single (Participant).
• Phase: Phase 3

Countries of recruitment

Belgium, Czechia, Denmark, Germany, Greece, Italy, Netherlands, Romania, Serbia, Spain, Turkey

Contacts

• Name: Evangelos Terpos, Prof
• Affiliation: Department of Clinical Therapeutics, University of Athens, School of Medicine, Athens, Greece

Key inclusion & exclusion 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 based on the investigator's determination of response as
defined by the modified IMWG criteria) to prior therapy.

5. 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.

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 (=4.65 mmol/L); (transfusions are not permitted to
reach this level);

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.

Because of the embryo-fetal risk of pomalidomide, all subjects must adhere to the
pomalidomide pregnancy prevention program applicable in their region. Investigators should
comply with the local label for pomalidomide for specific details of the program.

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, before C1D1 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


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Multiple Myeloma

Intervention(s)

Drug: Daratumumab

Drug: Dexamethasone

Drug: Pomalidomide

Primary Outcome(s)

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)]]

Secondary Outcome(s)

Daratumumab pharmacokinetic concentrations (Daratumumab IV and Dararatumumab SC) [Time Frame: IV: Day 1 of cycles 1,3,7 predose and at the end of Infusion and at 4 and 8 weeks after the last dose. SC: Days 1,4 of cycles 1,3, Day 1 of cycles 5,7,12 and at 4 and 8 weeks after the last dose]

MRD negativity rate [Time Frame: Frame: From Randomization until PD (approximately up to 3 years). Assessed at suspected CR and, 6, 12, 18, 24 months post CR/sCR and every 12 months thereafter in subjects with CR until PD]

Time to response [Time Frame: Assessed monthly from randomization up to first documented CR or PR (approximately up to 3 years)]

CR or better rate [Time Frame: Assessed monthly from Randomization until PD, (approximately up to 3 years)]]

Duration of response [Time Frame: Assessed monthly from Randomization until PD, (approximately up to 3 years)]

Overall survival [Time Frame: From randomization until death from any cause (up to 5 years)]

VGPR or better rate [Time Frame: Assessed monthly from Randomization until PD, (approximately up to 3 years)]]

• Scale and domain scores of the EORTC QLQ-C30 and EORTC QLQ-MY20 [Time Frame: Day 1 of each treatment cycle, at end of treatment, and every 4 weeks post treatment until PD (approximately up to 3 years)]

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

Daratumumab immunogenicity, rHuPH20 immunogenicity in subjects who receive Daratumumab SC [Time Frame: IV: Day 1 of first cycle predose, Day 1 of cycle 7 predose and at 4 and 8 weeks after the last dose (approx up to 3 years), SC and rHuPH20: Day 1 of cycle 1, 5, 7, 12 predose and at 4 and 8 weeks after the last dose]

EQ-5D-5L health utility values [Time Frame: Day 1 of each treatment cycle, at end of treatment, and every 4 weeks post treatment until PD (approximately up to 3 years)]

Immunomodulatory effects of daratumumab on T cells [Time Frame: Day 1 of cycles 1 , 3, 6, 12 predose and at suspected CR and at PD (approximately up to 3 years)]

Overall response rate [Time Frame: Assessed monthly from Randomization until PD, (approximately up to 3 years)]]

Safety (adverse events) [Time Frame: Continuously throughout the study, starting from informed consent until 30 days after last study treatment (approximately up to 3 years)]

Secondary ID(s)

EMN14/54767414MMY3013

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Janssen Research & Development, LLC