A phase 2, multicenter, multi-cohort, open-label study of pomalidomide in combination with
low-dose dexamethasone or pomalidomide in combination with low-dose dexamethasone and
daratumumab in subjects with relapsed or refractory multiple myeloma following lenalidomide
based therapy in the first or second line setting.
This trial will assess, Overall Response Rate (ORR), Overall Survival (OS), Progression-Free
Survival (PFS), Duration of Response (DoR), Time to Response (TTR), Time to Progression(TTP)
- Subjects must satisfy the following criteria to be enrolled in the study:
1. Adults (age ≥ 18 years at the time of signing the ICD) with documented diagnosis of
MM and measurable disease (serum M-protein ≥ 0.5 g/dL or urine M-protein ≥ 200 mg/24
2. Subjects enrolling in Cohort A (Pom+LD-dex) must have received 2 prior treatment
lines of anti-myeloma therapy. Subjects enrolling in Cohort B (Pom+Dara+LD-dex) must
have received 1 or 2 prior treatment lines of anti-myeloma therapy.
3. All subjects must have received prior treatment with LEN or a LEN-containing regimen
for at least 2 consecutive cycles as the most recent treatment regimen.
4. All subjects must have documented disease progression during or after their last
5. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status
score of 0, 1, or 2.
6. Subjects must understand and voluntarily sign an ICD prior to any study related
assessments/procedures being conducted.
7. Subjects must be able to adhere to the study visit schedule and other protocol
8. All subjects must provide an adequate bone marrow sample at screening that
definitively evaluates the presence or absence of myelodysplastic changes.
9. Females with child-bearing potential (FCBP†) must agree to use 2 reliable forms of
contraception* simultaneously or practice complete abstinence from heterosexual
contact for at least 28 days before starting study drug, while participating in the
study (including during dose interruptions), and for at least 28 days after study
treatment discontinuation and must agree to regular pregnancy testing during this
timeframe. For subjects enrolled in Cohort B, pregnancy prevention and testing will
continue until 3 months after last dose of daratumumab.
10. Females must agree to abstain from breastfeeding during study participation and 28
days after study drug discontinuation. Female subjects enrolled in Cohort B must
agree to abstain from breastfeeding and donating eggs during study participation and
until 3 months after last dose of daratumumab.
11. Males must agree to use a latex condom during any sexual contact with FCBP while
participating in the study and for 28 days following discontinuation from this study,
even if he has undergone a successful vasectomy. Male subjects enrolled in Cohort B
must agree to use a latex condom during any sexual contact with FCBP while
participating in the study and until 3 months after last dose of daratumumab.
12. Males must also agree to refrain from donating semen or sperm during the treatment
phase and for 28 days after discontinuation from this study treatment. Male subjects
enrolled in Cohort B must also agree to refrain from donating semen or sperm during
the treatment phase and until 3 months after last dose of daratumumab.
13. All subjects must agree to refrain from donating blood while on study therapy and for
28 days after discontinuation from this study treatment.
14. All subjects must agree not to share medication.
The presence of any of the following will exclude a subject from study enrollment:
1. Any of the following laboratory abnormalities:
- Absolute neutrophil count < 1,000/μL
- Platelet count < 75,000/μL for subjects in whom < 50% of bone marrow nucleated
cells are plasma cells; or a platelet count < 30,000/μL for subjects in whom ≥
50% of bone marrow nucleated cells are plasma cells.
- Severe renal impairment (Creatinine Clearance [CrCl] < 30 mL/min) requiring
- Corrected serum calcium > 11.5 mg/dL (> 2.8 mmol/L)
- Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior red blood cell transfusion or
recombinant human erythropoietin use is permitted)
- Serum SGOT/AST or SGPT/ALT > 3.0 x the upper limit of normal (ULN)
- Serum total bilirubin > 2.0 mg/dL (34.2 μmol/L); or > 3.0 x ULN for subjects
with hereditary benign hyperbilirubinemia
2. Prior history of malignancies, other than MM, unless the subject has been free of the
disease for ≥ 5 years. Allowed exceptions include the following:
- Basal or squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix or breast
- Incidental histological finding of prostate cancer (TNM [tumor, nodes,
metastasis] stage of T1a or T1b)
3. Previous therapy with pomalidomide or daratumumab
4. Hypersensitivity to thalidomide, LEN, or dex (this includes ≥ Grade 3 rash during
prior thalidomide or LEN therapy)
5. 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 4 weeks prior to
initiation of study treatment and are currently dependent on such treatment.
6. Subjects with any one of the following:
- Congestive heart failure (NY Heart Association Class III or IV)
- Myocardial infarction within 12 months prior to starting study treatment
- Unstable or poorly controlled angina pectoris, including Prinzmetal's variant
7. Subjects who received any of the following within 14 days of initiation of study
- Major surgery (kyphoplasty is not considered major surgery)
- Use of any anti-myeloma drug therapy
8. Use of any investigational agents within 28 days or 5 half-lives (whichever is
longer) of treatment, unless approved by the sponsor.
9. Incidence of gastrointestinal disease that may significantly alter the absorption of
10. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment
11. Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the ICD
12. Pregnant or breastfeeding females
13. Known human immunodeficiency virus (HIV) positivity; active infectious hepatitis A,
B, or C; or chronic hepatitis B or C
14. For subjects enrolling in Cohort B - Subject has known allergies, hypersensitivity to
mannitol, corticosteroids, monoclonal antibodies or human proteins, or their
excipients (refer to the Daratumumab IB), or known sensitivity to mammalian-derived