CLINICAL NEWS
Trial Roundup
ASH Clinical News’ Associate Editors select
clinical trials to keep an eye on.
LEUKEMIA
David Steensma, MD
Dana-Farber Cancer Institute
Phase 1b Acute Myelogenous Leukemia
(AML) Study with ABT-199 + Decitabine or
Azacitidine (Chemo Combo) (NCT02203773)
study design:
Phase Ib, non-randomized, open-label
safety/efficacy study
study start date: November 2014
estimated study completion date: May 2017
study status: Currently recruiting participants
estimated enrollment: 100
sponsor: AbbVie
This study is evaluating the safety of orally administered
ABT-199 (venetoclax) in combination with decitabine or
azacitidine and the preliminary efficacy of one of these
combinations in patients 65 years old or older with AML.
DNA hypomethylating agents such as decitabine and
azacitidine are commonly used to treat older, frailer
patients who decline intensive chemotherapy. ABT-199, a
potent and selective BCL-2 inhibitor, lowers the apoptosis threshold of neoplastic cells and sensitizes cells to
cytotoxic agents. It has striking activity as a single agent
in lymphoproliferative disorders, but the activity as a
monotherapy for AML is limited. However, combining
ABT-199 with chemotherapy may be synergistic in AML
and may be enough to give low-intensity therapy such
as decitabine or azacitidine in combination with ABT-199
in order to “push cells over the edge” and into apoptosis,
which would augment response rate without requiring
intensive chemotherapy.
Safety Study of Chimeric Antigen Receptor
Modified T-cells Targeting NKG2D-Ligands
(NCT02203825)
study design: Phase I, open-label, single-group safety study
study start date:
March 2015
estimated study completion date:
March 2019
Currently recruiting participants
estimated enrollment: 24
sponsor: Celdara Medical, LLC
study status:
This trial is evaluating chimeric-antigen receptor (CAR)
T cells (CM-CS1 T cells) and the safety and feasibility
of administering a single intravenous dose of CM-CS1
CAR T cells to patients with AML, myelodysplastic
syndrome (MDS)–refractory anemia with excess blasts,
and multiple myeloma (MM). Bioengineered CAR T
cells have shown striking activity in CD19+ lymphoid
neoplasms, but it has proven difficult to define a suitable target for CAR T cells in myeloid neoplasms that
do not result in profound, durable neutropenia. NKG2D
ligands are expressed by tumor cells in some patients
with AML and other hematologic neoplasms and may
be a potential target for cell-based immunotherapy.
In this study, patients with AML or MDS with excess
blasts for whom no standard therapy exists are being
administered autologous CAR T cells engineered to
recognize NKG2D ligands. Patients with relapsed and/
or refractory MM are also eligible.
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ASH Clinical News
SGI-110 in Adults with Untreated Acute
Myeloid Leukemia (AML), Not Considered
Candidates for Intensive Remission
Induction (NCT02348489)
The Designer D-Dimer Deep Vein
Thrombosis Diagnosis (4D) Study
study design:
study start date:
Phase III, randomized, open-label, parallelassignment safety/efficacy study
study start date: March 2015
estimated study completion date: December 2017
study status: Currently recruiting participants
estimated enrollment: 800
sponsor: Astex Pharmaceuticals
This study is comparing the efficacy and safety between
SGI-110 (guadecitabine) and treatment choice in adults
with previously untreated AML who are not considered
candidates for intensive remission induction chemotherapy.
SGI-110 is a hypomethylating agent that is a dinucleotide
combination of decitabine and deoxyguanosine; it appears
to have improved pharmacokinetic and pharmacodynamic
behavior compared with decitabine. In this study, 800
patients (age 75 years old or older) with newly diagnosed
AML or those with organ dysfunction or poor performance
status, will be randomized to receive SGI-110, decitabine, or
azacitidine. The primary endpoint is survival.
BLEEDING DISORDERS
(NCT02038530)
study design: Phase III, prospective, observational, cohort study
February 2014
December 2016
study status: Currently recruiting participants
estimated enrollment: 1,500
sponsor: Eastern McMaster University
estimated study completion date:
This study will assess a new diagnostic management
strategy for suspected deep-vein thrombosis (DVT) in
outpatients. The strategy is designed to reduce the use
of ultrasound testing on the day of presentation and
reduce repeat ultrasound testing a week after an initial
normal test. Less ultrasound testing will be performed
because more patients will have DVT excluded by
combinations of Clinical Pretest Probability and D-dimer
results on the day of presentation. In those who still
need an ultrasound, a repeat ultrasound conducted a
week after a normal result will only be performed if the
D-dimer result is markedly abnormal at initial presentation. The safety of this management strategy will
be determined by a very low rate of proximal DVT or
pulmonary embolism (PE) during 90 days of follow-up
in patients who had anticoagulant therapy withheld in
response to negative diagnostic testing.
Alice Ma, MD
University of North Carolina School of Medicine
A Study to Evaluate the Efficacy and Safety
of Rivaroxaban Venous Thromboembolism
(VTE) Prophylaxis in Ambulatory Cancer
Participants (NCT02555878)
study design:
Phase III, randomized, double-blind, parallelassignment safety/efficacy study
study start date: September 2015
estimated study completion date: June 2017
study status: Currently recruiting participants
estimated enrollment: 700
sponsor: Janssen Research & Development, LLC
This superiority study is comparing the efficacy and
safety of rivaroxaban with placebo for primary prophylaxis
of venous thromboembolism (VTE) in ambulatory adult
participants with various cancer types who are scheduled
to initiate systemic cancer therapy. The study consists of
three phases: 1) screening phase (14 days); 2) double-blind
treatment phase (180 days); and 3) follow-up phase (30
days). The duration of participation in the study for each
participant is approximately 32 weeks.
The pu rpose of this study is to demonstrate that rivaroxaban is superior to placebo for reducing the risk of the
primary composite outcome (symptomatic lower-extremity proximal DVT, asymptomatic lower-extremity proximal
DVT, symptomatic upper-extremity DVT, symptomatic
non-fatal PE, incidental PE, and VTE-related death) in
adults who are at high risk for developing a VTE.
The primary endpoint is time from randomization
to first occurrence of the composite outcome. The
primary safety objective is to assess the major bleeding events as defined by the International Society on
Thrombosis and Hemostasis.
Apixaban for the Prevention of Venous
Thromboembolism in Cancer Patients
(AVERT) (NCT02048865)
study design:
Phase II, randomized, double-blind parallelassignment safety/efficacy study
study start date: January 2014
estimated study completion date: January 2017
study status: Currently recruiting participants
estimated enrollment: 574
sponsor: Ottawa Hospital Research Institute
Cancer patients have an increased risk of developing blood clots in the veins compared with non-cancer
patients. The patients who do develop blood clots can
face reduced life expectancy, delayed cancer treatment,
and decreased quality of life. Prevention is the most
effective way to decrease the complications associated
with blood clots in the veins. Although previous clinical
trials have shown some benefit to using medication to
prevent blood clots in the veins in ambulatory cancer patients, these studies have been inconclusive in demonstrating that existing blood thinners significantly reduce
the rate of blood clots in cancer patients. One possible
explanation relates to the fact that these studies have
included a large proportion of cancer patients who are
at low risk for developing blood clots in the veins. The
trial aims to identify patients who are at a high risk for
developing blood clots by using a validated tool at the
time of their cancer diagnosis. The identified high-risk
cancer patients will then be asked to participate in a trial
to test the safety and efficacy of apixaban. The primary
outcome is a first episode of objectively documented,
symptomatic, or asymptomatic VTE. Secondary outcomes include the rate of adverse events.●
February 2016