Annual Meeting Proceedings Part 1 - American Society of Clinical ...

TPS8110 General Poster Session (Board #40C), Mon, 1:15 PM-5:15 PM
Phase III study of investigational MLN8237 (alisertib) versus investigator’s
choice in patients (pts) with relapsed/refractory (rel/ref) peripheral T-cell
lymphoma (PTCL). Presenting Author: Owen O’Connor, Center for Lymphoid
Malignancies, Columbia University Medical Center, New York, NY
Background: PTCL is a rare form of aggressive non-Hodgkin lymphoma
(NHL), accounting for 5–20% of NHL diagnoses. Standard NHL therapies
developed primarily for B-cell lymphomas are not optimal for PTCL and
early relapse is common. Current treatments for rel/ref PTCL include
pralatrexate, romidepsin, and gemcitabine; however, outcomes remain
poor. The oral, investigational drug, MLN8237, is a selective inhibitor of
Aurora A kinase (AAK) – a key mitotic regulator that is overexpressed or
amplified in various human tumors. Emerging clinical data from a phase II
study of single agent MLN8237 in rel/ref aggressive T-cell lymphoma
(Friedberg et al, ASH 2011) support further clinical evaluation in this
indication. Methods: In this open-label, randomized, phase III study, a
maximum of 354 adults with rel/ref PTCL after �1 prior systemic cytotoxic
therapies will be enrolled at approximately 140 centers worldwide. Pts will
be randomized 1:1 to MLN8237 50 mg twice daily as an enteric coated
tablet on days 1–7 of 21-day cycles, or to investigator’s choice of:
pralatrexate 30 mg/m2 IV once weekly for 6 weeks in 7-week cycles;
romidepsin 14 mg/m2 IV on days 1, 8, and 15 of 28-day cycles; or
gemcitabine 1000 mg/m2 IV on days 1, 8, and 15 of 28-day cycles. Pts
with disease response/stabilization will be able to continue treatment
provided that clinical benefit is demonstrated and treatment is tolerable.
The expected study duration is 44 months. Primary endpoints are overall
response rate (complete response [CR] � partial response) and progression
free survival by International Working Group criteria (Cheson et al, 2007).
Secondary endpoints include CR rate, overall survival, time to progression,
time to response, duration of response, safety, and quality of life.
Exploratory endpoints include an evaluation of candidate biomarkers (such
as AAK protein expression levels and gene amplification, and the tumor
proliferative marker Ki-67) in tumor biopsies. This study is registered at
ClinicalTrials.gov: #NCT01482962.
TPS8112 General Poster Session (Board #40E), Mon, 1:15 PM-5:15 PM
ELOQUENT-2: A phase III, randomized, open-label trial of lenalidomide/
dexamethasone (Len/Dex) with or without elotuzumab (Elo) in relapsed or
refractory multiple myeloma (RR MM) (CA204-004). Presenting Author:
Sagar Lonial, Multiple Myeloma Research Consortium, Norwalk, CT/
Winship Cancer Institute of Emory University, Atlanta, GA
Background: MM remains incurable and patients (pts) typically relapse or
become refractory to current treatments. Novel regimens are needed to
improve pt outcomes. Elo is a humanized monoclonal IgG1 antibody
targeting the cell surface glycoprotein CS1, which is highly expressed on
�95% of MM cells. Len/Dex is approved for treatment of relapsed MM and
an objective response rate (ORR) of ~60% was reported in phase III trials of
this combination in RR MM. In a phase II study (N�73) of Elo (10 or 20
mg/kg) in combination with Len/Dex in pts with RR MM, the 10 mg/kg
group (n�36) demonstrated an ORR of 92% and median progression-free
survival (PFS) that was not reached after a median follow-up of 14.1
months. Encouraging activity was seen in patients with high-risk cytogenetics
and/or stage 2-3 disease. Based on these data, a randomized,
open-label phase III trial has been initiated to determine if the addition of
Elo to Len/Dex will improve PFS in patients with RR MM compared with
Len/Dex alone. Methods: Pts (N�640) with RR MM and 1-3 prior therapies
are eligible, including pts with mild or moderate renal impairment. Pts are
randomized in a 1:1 ratio to receive 28-day cycles of Len 25 mg PO (days
1-21) and Dex 40 mg PO (days 1, 8, 15 and 22) with or without Elo. Elo
dose and schedule is 10 mg/kg IV on days 1, 8, 15, 22 in the first 2 cycles
and on days 1 and 15 in subsequent cycles. Dex 8 mg IV � 28 mg PO is
used during the weeks with Elo. Treatment will continue until disease
progression, death, or withdrawal of consent. Patients will be followed for
tumor response every 4 weeks until progressive disease and then survival
every 12 weeks. The primary endpoint is PFS (90% power for a hazard ratio
[experimental to control arm] of 0.74) and the secondary endpoints are
ORR and overall survival. Exploratory endpoints are safety, time to
response, duration of response, time to subsequent therapy, health-related
quality of life, and pharmacokinetics and immunogenicity of Elo. Potential
biomarkers will also be assessed. As of January 10th, 2012, 107 pts were
enrolled and 68 pts were treated. NCT01239797.
Lymphoma and Plasma Cell Disorders
537s
TPS8111 General Poster Session (Board #40D), Mon, 1:15 PM-5:15 PM
Pilot study of MAGE-A3 protein vaccination and autologous stem cell
transplantation (autoSCT) as consolidation therapy for multiple myeloma
(MM). Presenting Author: Adam D. Cohen, Fox Chase Cancer Center,
Philadelphia, PA
Background: MAGE-A3 is a cancer-testis antigen (CT Ag) commonly
expressed in MM but not in normal non-gonadal tissues. MAGE-A3
inhibited p53-dependent and independent apoptosis in MM cells (Clin
Cancer Res 2011;17:4309), and spontaneous immunity against CT Ags in
MM patients was associated with favorable clinical outcomes (Blood
2007;109:1103; Blood 2008;112:3362), making it a rational target for
immunotherapy. In this study (NCT01380145), we are examining if a
recombinant (rec) MAGE-A3 protein vaccine � adjuvant combined with
vaccine-primed peripheral blood lymphocytes (PBL) can safely stimulate
antigen-specific immunity in MM patients undergoing autoSCT for consolidation
therapy. Methods: Patients meeting the following criteria are
eligible: within 12 months of diagnosis; MAGE-A� MM cells by immunohistochemistry;
achieving at least a very good partial response with induction
therapy; and meeting institutional criteria for autoSCT. One patient of a
planned cohort of sixteen has been enrolled. Six weeks before SCT,
subjects will receive their first vaccination (300 �g IM) and three weeks
later undergo leukopheresis to collect vaccine-primed PBL. They then
undergo stem cell mobilization followed by a standard melphalanconditioned
autoSCT. On day 3 after stem cell infusion, the unmanipulated,
primed PBL will be re-infused followed by the second recMAGE-A3
vaccination on day 10. An additional six vaccinations will be administered
on days 31, 52, 73, 94, 180, and 270 after autoSCT. The primary
objectives are safety and tolerability. The secondary objectives of cellular
and humoral immune responses and lymphocyte reconstitution will be
assessed by a validated series of quantitative assays using established
response criteria (PNAS 2008;105:1650). Success criteria based on
immune response have not been specified for this pilot study, though
induction of MAGE-A3 immunity in at least 50% of patients would merit
consideration for further evaluation of clinical efficacy.
TPS8113 General Poster Session (Board #40F), Mon, 1:15 PM-5:15 PM
ELOQUENT-1: A phase III, randomized, open-label trial of lenalidomide/
dexamethasone with or without elotuzumab in subjects with previously
untreated multiple myeloma (CA204-006). Presenting Author: Meletios A.
Dimopoulos, Hellenic Cooperative Oncology Group, Athens, Greece
Background: Elotuzumab (Elo) is a humanized monoclonal IgG1 antibody
targeting the cell surface glycoprotein CS1, which is highly expressed on
�95% of MM cells. In a MM xenograft mouse model, the combination of
Elo � lenalidomide (Len) significantly reduced tumor volume in a synergistic
manner compared with either agent alone. In a phase 2 study (N�73) of
Elo (10 or 20 mg/kg) in combination with Len and low-dose-dexamethasone
(Dex) in pts with RR MM, the 10 mg/kg dose group (n�36)
demonstrated objective response rates (ORR) of 92% in all pts, and 100%
in pts who had received only 1 prior therapy (n�16). The higher response
rate in pts with fewer prior lines of therapy provides a rationale for
investigating this combination earlier in the disease course. This randomized,
open-label, phase 3 trial will determine if the addition of Elo to
Len/Dex improves progression-free survival (PFS) in pts with newly diagnosed,
untreated MM. Methods: Pts (N�750) with newly diagnosed
symptomatic MM ineligible for stem cell transplant will be randomized in a
1:1 ratio to receive 28-day cycles of Len 25 mg PO (days1-21) and Dex 40
mg PO (days 1, 8, 15 and 22) with or without Elo. Elo dose and schedule is
10 mg/kg IV on days 1, 8, 15, 22 in the first 2 cycles and on days 1 and 15
of cycles 3-18 followed by 20 mg/kg on day 1 of cycle 19 onward. Dex 8 mg
IV � 28 mg PO is used during the weeks with Elo. Treatment will continue
until disease progression, death, or withdrawal of consent. Pts will be
followed up for response every 4 weeks until progressive disease and for
survival every 16 weeks. The primary endpoint is PFS (90% power for a
hazard ratio [experimental to control arm] of 0.74) and the secondary
endpoints are ORR and overall survival. Exploratory endpoints are safety,
time to response, duration of response, time to subsequent therapy,
health-related quality of life, and pharmacokinetics and immunogenicity of
Elo. Potential biomarkers will also be assessed. As of January 1, 2012, 13
pts were enrolled and 9 pts were treated. NCT01335399.
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