The primary objective is:To evaluate the efficacy of pomalidomide (CC-4047) monotherapy in subjects with refractory orrelapsed and refractory multiple myeloma who discontinued treatment after being treated withdexamethasone alone (Treatment Arm B)…
ID
Source
Brief title
Condition
- Skeletal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is overall response rate (ORR) using the new International
Myeloma
Working Group Uniform (IMWG) response criteria. An analysis comparing the
results of
response assessments judged by the EMBT criteria (Blade, 1998) to those of the
IMWG criteria
will also be performed.
Secondary outcome
- Safety (type, frequency, and severity of adverse events [AEs], and
relationship of
AEs to study drug)
- Progression-free survival (PFS)
- Time to progression (TTP)
- Duration of response
- Overall survival (OS)
Background summary
The phase 1 segment of the Celgene sponsored Study CC-4047-MM-002 determined the
maximum tolerated dose (MTD) of pomalidomide in this subject population to be 4
mg/day. In
Study CC-4047-MM-002, responses were seen in both the 2 and 4-mg dose levels;
however, the
best response rate and duration of response was associated with a dose of 4
mg/day of
pomalidomide (the starting dose in the present trial) in a cyclic 21 out of
28-day dosing schedule.
This regimen will allow a one-week rest period per every 28-day cycle for bone
marrow
recovery to minimize the occurrence of neutropenia, which were the
DLTs during the phase 1 segment of the study. The Phase 2 segment of the study
CC-4047-
MM-002 was started in November 2009 and as of September 22, 2010 enrolment has
been
completed and 221 subjects have been enrolled.
The results of a number of investigator-initiated studies conducted thus far
indicate that
pomalidomide produces responses in subjects who are refractory to lenalidomide,
another
IMiDs® compound, aligning with the non-clinical results observed in
lenalidomide-resistant cells
(Adams, 2009). The phase 2 study using pomalidomide plus low-dose dexamethasone
for
relapsed multiple myeloma (Lacy, 2009; 2010) showed a response rate of 40% in
lenalidomiderefractory
patients. These results imply a non-cross resistance for pomalidomide and
suggesting
a special role for this drug in the treatment of refractor/relapsed patients.
Pomalidomide, to date,
has an acceptable safety profile, and the most common hematological toxicity
experienced by
subjects is neutropenia (non-febrile), which can be managed by dose reductions
or interruptions and growth factors.
The most common non-hematological toxicities are fatigue and pneumonia.
Based on these published data, pomalidomide would be expected to provide
clinical benefit to
such subjects with high unmet medical need who have very limited available
treatment options.
This companion study will provide more information about the safety and
efficacy of singleagent
pomalidomide in patients who are refractory or relapse after multiple lines of
therapy
Study objective
The primary objective is:
To evaluate the efficacy of pomalidomide (CC-4047) monotherapy in subjects with
refractory or
relapsed and refractory multiple myeloma who discontinued treatment after being
treated with
dexamethasone alone (Treatment Arm B) in Study CC-4047-MM-003 due to the
development of
documented disease progression during treatment.
The secondary objective is:
To evaluate the safety of pomalidomide monotherapy in subjects with refractory
or relapsed and
refractory multiple myeloma who discontinued treatment after being treated with
dexamethasone
alone (Treatment Arm B) in Study CC-4047-MM-003 due to the development of
documented
disease progression during treatment.
Study design
Study CC-4047-MM003/C is the companion study for clinical trial CC-4047-MM-003.
This is a
multi-center, open-label, single-arm study to evaluate the safety and efficacy
of pomalidomide
monotherapy in subjects with refractory or relapsed and refractory multiple
myeloma. This
companion study will enroll subjects who have discontinued study treatment with
dexamethasone alone (Treatment Arm B) in the CC-4047-MM-003 trial due to disease
progression. Subjects who have discontinued study treatment with pomalidomide
plus
dexamethasone (Treatment Arm A) will not be eligible to participate in the
companion study.
The key inclusion criteria in the CC-4047-MM-003/C trial limits the enrollment
to all evaluable
subjects in the CC-4047-MM-003 study who discontinue therapy after at least
starting the second cycle of
dexamethasone alone (Treatment Arm B) due to development of documented disease
progression according to the IMWG criteria and as decided by an IRAC. Subjects
who
discontinue therapy with dexamethasone alone (Treatment Arm B) due to toxicity
or intolerance
to dexamethasone and not due to development of confirmed progressive disease
will not be
eligible to enroll in the companion trial.
It is estimated that 30% to 60% of subjects in the control arm of Study
CC-4047-MM-003
(dexamethasone alone; n = 142) could be enrolled in the companion study. Thus
the estimated
number of subjects in Study CC-4047-MM-003/C will be in the range of 42-85.
Enrollment of
subjects will be opened to all investigator sites that participated in Study
CC-4047-MM-003 (EU,
Switzerland, Russia, Australia and Canada.
Figure 1 summarizes the flow and the transition between both CC-4047-MM-003 and
CC-4047-
MM-003/C. For subjects with treatment discontinuation visit assessments for
Study CC-4047-MM-003 performed within <= 28 days of screening for Study
CC-4047-MM-003/C, any overlapping assessments do not have to be repeated for
screening in this study if approved by the Study Team. If the assessments were
done > 28 days from screening, these assessments need to be repeated at the
screening phase.
Subjects will not be eligible to enroll in the companion study if 120 days or
more have passed
since their discontinuation from CC-4047-MM-003 study. No other anti-myeloma
therapies are
allowed from the time of disease progression on CC-4047-MM-003 to the time of
treatment
initiation in the companion study.
The oral pomalidomide starting dose is 4 mg daily on Days 1-21 every 28 days.
Dosing
interruptions and reductions are permitted throughout the study. All subjects
participating in the
trial will continue treatment until they stop taking the study medication
because of disease progression or another reason. For all subjects who enroll
into this study, study visits and serial measurements of safety and
efficacy will be performed as outlined in Table 1 Table of Events.
Intervention
/
Study burden and risks
The patient needs to visit the hospital as described in E2. The folloWing study
procedures will be done as described in the
schedule on page 31 of the protocol:
- bone marrow biopsy or aspirate
- ECG
- Physical examination
- Pregnancy test
- Blood drawing
- Completion of questionnaires
Risks of the study are described in the appendix of the informed consent.
Morris Avenue 86
Summit NJ 07901
US
Morris Avenue 86
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US
Listed location countries
Age
Inclusion criteria
1. Subjects with refractory or relapsed and refractory multiple myeloma who were enrolled
in Study CC-4047-MM-003 and discontinued study therapy with dexamethasone alone
(Treatment Arm B) after at least starting the second cycle of dexamethasone treatment and due to
development of documented disease progression according to the IMWG criteria and as
decided by an IRAC.
2. Must be >= 18 years at the time of signing the informed consent form.
3. The subject must understand and voluntarily sign an informed consent document prior to
any study related assessments/procedures being conducted. The only exception is if a
skeletal survey was performed within 90 days prior to the start of Cycle 1, then a new
survey will not be required.
4. Must be able to adhere to the study visit schedule and other protocol requirements.
5. Subjects must have documented diagnosis of multiple myeloma and have measurable
disease (serum M-protein >= 0.5 g/dL or urine M-protein >= 200 mg/24 hours).
6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
7. Females of childbearing potential (FCBP*) must agree to utilize two 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 dose interruptions), and for at least 28 days after study treatment discontinuation and must agree to regular pregnancy testing during this timeframe.
8. Females must agree to abstain from breastfeeding during study participation and 28 days
after study discontinuation.
9. 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.
10. Males must also agree to refrain from donating semen or sperm while on pomalidomide
and for 28 days after discontinuation from this study treatment.
11. All subjects must agree to refrain from donating blood while on study drug and for 28
days after discontinuation from this study treatment.
12. All subjects must agree not to share study medication.
Exclusion criteria
1. Subjects with multiple myeloma who were not treated as a part of Study CC-4047-MM-
003 (Arm B).
2. Subjects who received any anti-myeloma or anti-cancer therapies within the last 14 days of wash-out period before initiation of study treatment.
3. Subjects who discontinued CC-4047-MM-003 study >=120 days.
4. Subjects who initiate another anti-myeloma therapy from the time of disease progression
on study CC-4047-MM-003 to the time of treatment initiation in the companion study.
5. Any of the following laboratory abnormalities:
- Absolute neutrophil count (ANC) < 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
- Creatinine Clearance < 45 mL/min according to Cockcroft-Gault formula (If creatinine clearance calculated from the 24-hour urine sample is >=45 ml/min, patient will qualify for the trial)
- Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L)
- Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior RBC transfusion or recombinant human
erythropoietin use is permitted)
- Serum SGOT/AST or SGPT/ALT > 3.0 x 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 hyperbilirubineamia
6. Prior history of malignancies, other than MM, unless the subject has been free of the
disease for >= 5 years. Exceptions include the following:
- Basal or Squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix or breast
- Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)
7. Hypersensitivity to thalidomide or lenalidomide. (This includes >= Grade 3 rash during prior thalidomide or lenalidomide therapy).
8. Peripheral neuropathy >= Grade 2.
9. 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.
10. Subjects who are planning for or who are eligible for stem cell transplant.
11. 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 variant angina
pectoris
12. Subjects who received any of the following within the last 14 days of initiation of study
treatment:
- Plasmapheresis
- Major surgery (kyphoplasty is not considered major surgery)
- Radiation therapy
13. Use of any investigational agents within 28 days or 5 half-lives (whichever is longer) of
treatment.
14. Subjects with chronic conditions such as rheumatoid arthritis, multiple sclerosis and
lupus, which likely need additional steroid or immunosuppressive treatments in addition to the study treatment.
15. Any condition including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study.
16. Incidence of gastrointestinal disease that may significantly alter the absorption of
pomalidomide.
17. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment.
18. Any serious medical condition, laboratory abnormality, or psychiatric illness that would
prevent the subject from signing the informed consent form.
19. Pregnant or breastfeeding females.
20. Known HIV positivity or active infectious hepatitis A, B or C.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-023343-16-NL |
| ClinicalTrials.gov | NCT01324947 |
| CCMO | NL36039.078.11 |