CLINICAL NEWS
Trial Roundup
ASH Clinical News’ Associate Editors select
clinical trials to keep an eye on.
LEUKEMIA
LYMPHOMA & MYELOMA
David Steensma, MD
Dana-Farber Cancer Institute
Keith Stewart, MBChB, MBA
Mayo Clinic, Arizona
In a phase II study of 64 patients with newly diagnosed
diffuse large B-cell lymphoma (DLBCL) conducted at Mayo
Clinic, lenalidomide combined with RCHOP (R2CHOP) was
well tolerated and resulted in a high complete response
rate and encouraging progression-free and overall survival.
Importantly, the addition of lenalidomide to RCHOP appeared to be particularly beneficial in the non-germinal
center B-cell (GCB) subtype of DLBCL compared with
historical controls – essentially overcoming the negative
prognostic impact of activated B-cell (ABC) phenotype.
These promising results led to the development of
randomized front-line studies that will answer questions
about the role of R2CHOP in the treatment of patients
with newly diagnosed DLBCL. The three trials below
investigate lenalidomide combinations with chemoimmunotherapy in aggressive lymphoma, with a particular focus
on molecular tumor profiling.
A Safety and Tolerability Study of
Crenolanib in Combination With
Chemotherapy in Newly Diagnosed Acute
Myeloid Leukemia Patients With FLT3
Mutations (NCT02283177)
Study Design: Non-randomized, open-label, parallelassignment, safety study
Study Start Date: January 2015
Estimated Study Completion Date: July 2017
Study Status: Currently recruiting participants
Estimated Enrollment: 48
Sponsor: Arog Pharmaceuticals, Inc.
In the Alliance Cooperative Group–led RATIFY trial,
the combination of conventional anthracycline/cytarabine induction and cytarabine consolidation with
the multi-kinase inhibitor midostaurin was found to
improve survival in patients with FLT3-mutant acute
myeloid leukemia (AML), compared to chemotherapy
without midostaurin. Similarly, the European SorAML study showed improved relapse-free survival in
AML, including FLT3-mutant AML, when combining
the multikinase inhibitor sorafenib with conventional
chemotherapy. This study tests a novel FLT3/PDGFR
inhibitor, crenolanib, given sequentially during standard
induction and consolidation chemotherapy in patients
with newly diagnosed AML with FLT3-activating mutations. Crenolanib inhibits both wild-type FLT3 and type
1 mutants.
Rituximab and Combination Chemotherapy
With or Without Lenalidomide in Treating
Patients With Newly Diagnosed Stage II-IV
Diffuse Large B Cell Lymphoma (NCT01856192)
Study Design: Randomized, open-label, parallel-assignment, efficacy study
Study Start Date: August 2013
Estimated Study Completion Date: January 2018
Study Status: Currently recruiting participants
Estimated Enrollment: 345
Sponsor: National Cancer Institute
Study of Orally Administered AG-881 in
Patients With Advanced Hematologic
Malignancies With an IDH1 and/or IDH2
Mutation (NCT02492737)
This is an NCI-sponsored, multicenter, U.S. Intergroup
study led by ECOG that randomizespatients with newly
diagnosed stage 2-4 DLBCL to RCHOP or R2CHOP. Patients with all DLBCL subtypes are eligible for inclusion,
regardless of molecular subtype, and the study will analyze outcomes based on molecular subtype of DLBCL.
Study Design: Open-label, single-group assignment,
safety/efficacy study
Study Start Date: July 2015
Estimated Study Completion Date: March 2018
Study Status: Currently recruiting participants
Estimated Enrollment: 50
Sponsor: Agios Pharmaceuticals, Inc.
Efficacy and Safety Study of Lenalidomide
Plus R-CHOP Chemotherapy Versus
Placebo Plus R-CHOP Chemotherapy in
Untreated ABC Type Diffuse Large B-Cell
Lymphoma (ROBUST) (NCT02285062)
IDH1 or IDH2 mutations are present in 20 to 30 percent
of patients with karyotypically normal AML and in a
small proportion of patients with MDS and other myeloid neoplasms. AG221 and AG120 are orally available
IDH2 and IDH1 inhibitors, respectively, and have induced
responses – including complete responses in IDHmutant AML. The purpose of this phase I, multicenter
study is to evaluate the safety, pharmacokinetics,
pharmacodynamics, and clinical activity of AG-881, an
IDH1/IDH2 inhibitor, in advanced hematologic malignancies that harbor an IDH1 or IDH2 mutation.
ASHClinicalNews.org
Study Design: Randomized, double-blind, parallel-assignment, safety/efficacy study
Study Start Date: January 2015
Estimated Study Completion Date: September 2022
Study Status: Currently recruiting participants
Estimated Enrollment: 560
Sponsor: Celgene Corporation
The ROBUST trial is a multicenter, global study focusing
on patients with newly diagnosed ABC DLBCL. Eligible
patients with stage 2-4 DLBCL are randomized to
R2CHOP or RCHOP plus placebo.
R-ICE and Lenalidomide in Treating
Patients With First-Relapse/Primary
Refractory Diffuse Large B-Cell Lymphoma
(NCT02628405)
Study Design: Open-label, single-group assignment,
safety/efficacy study
Study Start Date: December 2015
Estimated Study Completion Date: November 2020
Study Statu 3