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
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 and Cohort C
(POM+DARA+LD-dex) must have received 1 or 2 prior treatment lines of anti-myeloma
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 and
Cohort C, 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
and Cohort C 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 and Cohort C 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
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 and Cohort C 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
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 more than 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
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 angina pectoris
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 including for the treatment of multiple myeloma
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 oral
absorption of Pomalidomide.
10. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment
11. Any serious medical condition, laboratory abnormality, or psychiatric illness,
that would preclude participation in the study, or interfere with interpretation
of the study results
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
All subjects will be tested for hepatitis B surface antigen (HBsAg), hepatitis B
surface antibody (antiHBs), and hepatitis B core antibody (antiHBc). Subjects
with the following serological testing are considered not eligible:
- HBsAg positive
- HBsAg negative, anti-HBs positive and/or anti-HBc positive and detectable
- Subjects who are HBsAg negative, anti-HBs positive, and/or anti-HBc
positive, viral DNA negative are eligible. For these subjects, DNA
monitoring and prophylactic medication for HBV reactivation are recommended
per local practice.
- Subjects who are seropositive because of hepatitis B virus vaccination are
eligible (anti-HBs positive, anti-HBc negative, and HBsAg negative).
All subjects will be tested for hepatitis C antibody. Subjects are not eligible
if known seropositive for hepatitis C virus.
• Subjects who are hepatitis C antibody positive but show no detectable viral RNA
for 6 months prior to initiation of study treatment are eligible.
14. For subjects enrolling in Cohort B and Cohort C - 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 products.