The study will look at patients with relapsed (returned after prior treatment) and refractory (not responsive to prior treatment) multiple myeloma. The research aims to compare a new drug called elotuzamab combined with standard of care (…
ID
Source
Brief title
Condition
- Plasma cell neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective is to compare "progression free survival" (PFS) between
the control treatment arm and the investigational treatment arm.
Secondary outcome
The secondary objectives are:
1) To compare the "objective response rate" between the control treatment arm
and the investigational treatment arm.
('Objective Response Rate' is the percentage of patients whose cancer shrinks
or disappears after treatment.)
2) To compare "overall survival rate" between the control treatment arm and the
investigational treatment arm.
( 'Overall survival rate' is the percentage of people in a clinical trial who
are still alive for a certain period of time after they were diagnosed with or
started treatment for a disease, such as cancer.)
Background summary
This study is for patients with relapsed (returned after prior treatment) and
refractory (not responsive to prior treatment) multiple myeloma. This clinical
research study is being supported by AbbVie and Celgene and sponsored by
Bristol-Myers Squibb. The name of this investigational new drug is elotuzumab.
Among hematologic malignancies, multiple myeloma is the second most prevalent
blood cancer after non-Hodgkin lymphoma, representing 10% of hematologic
malignancies. The incidence of multiple myeloma in Europe is 4.5 to
6.0/100,000/year and the mortality is 4.1/100,000/year. The incidence of
multiple myeloma increases with advancing age and the median age of diagnosis
in Europe between 65 and 70 years.
Currently approved treatments commonly used for patients with relapsed /
refractory multiple myeloma include proteosome inhibitor based therapies,
immune modulatory drug based therapies (e.g. pomalidomide) and histone
deacetylase inhibitors. There is no cure and current therapies can only slow
disease progression, prolong survival, and minimize symptoms. While recent
advances in the use of high-dose chemotherapy, targeted therapeutics, and stem
cell transplantation have improved overall and event-free survival, the
majority of patients with myeloma will relapse and disease progression is
expected for all but a small percentage. Multiple myeloma is associated with
morbidity and mortality, thus reflecting a significant unmet medical need.
The purpose of this study is to determine if elotuzumab given with pomalidomide
and dexamethasone is more effective in the treatment of relapsed and refractory
multiple myeloma compared with a standard treatment of pomalidomide and
dexamethasone alone.
The study will also determine the safety of elotuzumab when given with
pomalidomide and dexamethasone compared with pomalidomide and dexamethasone
alone and further investigate the pharmacokinetics of elotuzumab.
Elotuzumab is a manufactured protein directed against a target found on
multiple myeloma cells. Elotuzumab was observed to kill myeloma cells in
laboratory studies, and results of earlier clinical studies in patients with
myeloma showed encouraging results when used in combination with other drugs
It is currently unknown whether the combination of elotuzumab with standard
therapy is better than standard therapy alone.
The dose selection of 10 mg/kg and 20mg/kg of elotuzumab for this study is
based on data from the phase 1 and 2 studies that have been conducted assessing
pharmacokinetics (PK), safety, and preliminary efficacy of elotuzumab.
Pomalidomide is a drug that changes the immune system and it may also reduce or
prevent the development of tiny blood vessels that help support tumour growth.
Therefore it may reduce or prevent the growth of cancer cells. Pomalidomide in
combination with dexamethasone is approved by the United States, Canada,
European Union and Japan for the treatment of patients with relapsed and
refractory multiple myeloma who have received at least 2 prior multiple myeloma
therapies.
Dexamethasone is a steroid that is commonly used, either alone or in
combination with other drugs, to treat multiple myeloma.
The combination of pomalidomide and dexamethasone was approved by regulatory
authorities for the treatment of relapsed and refractory myeloma. It is a
commonly used regimen in this setting.
Study objective
The study will look at patients with relapsed (returned after prior treatment)
and refractory (not responsive to prior treatment) multiple myeloma.
The research aims to compare a new drug called elotuzamab combined with
standard of care (dexamethasone plus pomalidomide) VERSUS standard of care
chemotherapy (dexamethasone plus pomalidomide) to see which treatment helps
patients live longer without their cancer
getting worse, which is known as Progression Free Survival (PFS).
The study aims to demonstrate an improvement in median PFS from 4.0 months in
the control arm to a median PFS of 7.0 months in the investigational elotuzamab
arm.
Study design
This is a phase 2 multicenter, open-label, randomized study designed to
evaluate the clinical benefit of the investigational combination therapy of
elotuzumab, pomalidomide, and dexamethasone (E-Pd; the elotuzumab arm) when
compared to pomalidomide and dexamethasone (Pd; the control arm) in subjects
with relapsed and refractory multiple myeloma.
114 subjects will be randomized in a 1:1 ratio to receive either
pomalidomide/dexamethasone (Pd) or elotuzumab/pomalidomide/dexamethasone
(E-Pd).
The randomization will be stratified by:
1) Number of lines of previous therapy (2-3 previous therapies versus 4
previous therapies )
2) ISS stage at study entry (Stage I-II versus Stage III) (Note: ISS =
International Staging System for Multiple Myeloma)
The study design schematic diagram can be viewed in Table 3.1-1 on Page 36 of
the Protocol.
Following treatment, patients will enter the "Follow-up" phase and will be
assessed every 4 weeks for tumour response until PD ("Progressive Disease") is
observed. After PD, patients will then have "survival follow-up" visits by
telephone at a minimum of every 12 weeks.
At the conclusion of the study, subjects who continue to demonstrate clinical
benefit will be eligible to receive study drug. Study drug will be provided via
an extension of the study, a rollover study requiring approval by responsible
health authority and ethics committee or through another mechanism at the
discretion of BMS.
Intervention
Control Arm:
1) Pomalidomide: 4 mg PO QD Days 1-21 of each cycle
2) Dexamethasone:
* Subjects years old: 40 mg PO Days (1, 8, 15 and 22) of each cycle
* Subjects > 75 years old: 20 mg PO Days (1, 8, 15 and 22) of each cycle
Elotuzumab Arm:
1) Elotuzumab:
* Cycle 1 - 2: 10 mg/kg IV Days 1, 8, 15 and 22 of each cycle
* Cycle 3 and beyond: 20mg/kg IV Day 1 of each cycle
2) Pomalidomide: 4 mg PO QD Days 1-21 of each cycle
3) Dexamethasone: Days 1, 8, 15 and 22 of each cycle
* Subjects * 75 years old: weeks with elotuzumab dosing: 28 mg PO + 8 mg IV and
40 mg PO on non-elotuzumab dosing weeks
* Subjects > 75 years old: weeks with elotuzumab dosing: 8 mg PO + 8 mg IV and
20 mg PO on non-elotuzumab dosing weeks
Study burden and risks
As part of the trial, patients will be expected to attend multiple clinic
visits, where they will undergo physical examinations, vital sign measurements
(including oxygen saturation levels), blood tests for safety assessment,
pregnancy testing (for females of child bearing potential), and monitoring for
adverse events. In addition, patients will undergo radiographic assessment (by
CT or MRI) until disease progression or treatment discontinuation whichever
occurs later. Blood will also be collected at certain visits for research
purposes (PK, immunogenicity and biomarker studies). CT or MRI should be
performed at screening, if clinically indicated or if patient had a previous
extramedullary or bone plasmacytoma. Skeletal survey, by CT or MRI, for
metastatic disease will be performed within 28 days of starting treatment in
all subjects. Skeletal survey will be performed during the study if clinically
indicated
The frequency of visits and number of procedures carried out during this trial
would typically be considered over and above standard of care. These procedures
are conducted by medically trained professionals and every effort will be made
to minimise any risks or discomfort to the patient. Treatment for cancer often
has side effects, including some that are life-threatening.
Park Sanderson Road Uxbridge Business
Uxbridge UB8 1DH
GB
Park Sanderson Road Uxbridge Business
Uxbridge UB8 1DH
GB
Listed location countries
Age
Inclusion criteria
Subjects who are diagnosed with relapsed and refractory multiple myeloma
defined as:
(1) * 2 prior lines of therapy which must have included at least 2 consecutive
cycles of lenalidomide and a proteosome inhibitor alone or in combination.
(2) Documented refractory or relapsed and refractory multiple myeloma
(3) Refractory to proteosome inhibitor and lenalidomide, and to their last
treatment
(4) Relapsed and refractory patients had achieved at least a partial response
to previous treatment with proteosome inhibitor or lenalidomide, or both, but
progressed within 6 months, and were refractory to their last treatment.
(5) Measurable disease at screening
(6) Eastern Cooperative Oncology Group (ECOG) performance status * 2
Exclusion criteria
1) Target Disease Exceptions
a) Subjects with solitary bone or extramedullary plasmacytoma as the only
evidence of plasma cell dyscrasia.
b) Subjects with monoclonal gammopathy of undetermined significance, smoldering
multiple myeloma (SMM), amyloidosis, POEMS, or Waldenstrom*s macroglobulinemia
c) Subjects with active plasma cell leukemia
2) Medical History and Concurrent Diseases
a) Any uncontrolled or severe cardiovascular or pulmonary disease determined by
the investigator
b) Active infection that requires parenteral anti-infective treatment > 14 days
c) Unable to tolerate thromboembolic prophylaxis while on the study
d) Hypersensitivity reaction to prior IMiD (thalidomide or lenalidomide)
e) Grade 2 peripheral neuropathy (per NCI CTCAE v3.0)
f) Known active hepatitis A, B, or C
g) Known HIV infection
h) Gastrointestinal disease that may significantly alter the absorption of
pomalidomide
i) Prior or concurrent malignancy, except for the following:
i) Adequately treated basal cell or squamous cell skin cancer.
ii) Any cancer (other than in-situ) from which the subject has been disease
free for > 3 years prior to study entry.
3) Prior Therapy or Surgery
a) Prior treatment with pomalidomide.
b) Prior participation in an elotuzumab clinical trial
c) Use of any anti-myeloma drug therapy, within 14 days of the initiation of
study drug treatment or use of any experimental drug therapy or plasmapheresis
within 28 days (or 5 half-lives) whichever is longer of the initiation of study
drug treatment (includes dexamethasone).
d) Treatment with melphalan or monoclonal antibodies within 6 weeks of the
first dose of study drug
e) Prior autologous stem cell transplant within 12 weeks of the first dose of
study drug.
f) Prior allogeneic stem cell transplant except subjects who have completed the
stem cell transplant > 12 months prior to first dose of study drug, have no
history of graft versus host disease, and are not on topical or systemic
immunosuppressive therapy
g) Treatment with corticosteroids within 3 weeks of the first dose of study
drug, except for the equivalent of *10 mg prednisone per day or corticosteroids
with minimal to no systemic absorption or for short course (*4 days) of 40 mg
dexamethasone or equivalent for emergency use
h) Major cardiac surgery within 8 weeks prior to the first dose of study drug;
all other major surgery within 4 weeks prior to the first dose of study drug.
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 | EUCTR2014-003282-19-NL |
| CCMO | NL56316.029.16 |