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. The APOLLO Study
- Conditions
- Kahler's diseaseplasma cell myeloma10035227
- Registration Number
- NL-OMON52783
- Lead Sponsor
- European Myeloma Network (EMN)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 20
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
FLC >=10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio.
4. Subjects must have received prior anti-myeloma 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. All of the following laboratory test results during Screening:
a) Absolute neutrophil count >=1.0 × 109/L;
b) Hemoglobin level >=7.5 g/dL (>=4.65 mmol/L) (transfusions are not permitted to
reach this level);
c) 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 (transfusions are not permitted
to reach this level);
d) Alanine aminotransferase (ALT) level <=2.5 times the upper limit of normal
(ULN);
e) Aspartate aminotransferase (AST) level <=2.5 x ULN;
f) Total bilirubin level <=1.5 x ULN, (except for Gilbert Syndrome: direct
bilirubin <=1.5 × ULN);
g) Creatinine clearance >=30 mL/min (Appendix 6);
h) 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. Criterion (letter *g*) modified per Amendment 2:
11.1 Reproductive Status
a) 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 within 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.
b) Women must not be breastfeeding.
c) 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.
d) Males who are sexually active must al
1. Previous therapy with any anti-CD38 monoclonal antibody.
2. Previous exposure to pomalidomide.
3. Subject has received anti-myeloma 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. (Appendix 4).
8. Clinically significant cardiac disease, including:
a) 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).
b) Cardiac arrhythmia (Common Terminology Criteria for Adverse Events [CTCAE]
Grade 3 or higher) or clinically significant
electrocardiogram (ECG) abnormalities.
c) Electrocardiogram showing a baseline QT interval as corrected QTc >470 msec.
9. Criterion modified per Amendment 2:
9.1 Known:
a) Active hepatitis A
b) To be seropositive for hepatitis B (defined by a positive test for
hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (ie,
subjects who are positive
for antibodies to hepatitis B core antigen [antiHBc] and/or antibodies
to hepatitis B surface antigen [antiHBs]) must be screened using real-time
polymerase chain
reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those
who are PCR positive will be excluded. EXCEPTION: Subjects with serologic
findings
suggestive of HBV vaccination (antiHBs positivity as the only serologic
marker) AND a known history of prior HBV vaccination, do not need to be tested
for HBV
DNA by PCR.
c) To be seropositive for hepatitis C (except in the setting of a sustained
virologic response, defined as aviremia at least 12 weeks after completion of
antiviral therapy).10. Criterion Revised per Amendment 2
10.1 Known to be seropositive for human immunodeficiency virus.
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoint<br /><br>- * Progression-free survival</p><br>
- Secondary Outcome Measures
Name Time Method