ASH Clinical News Focus on Myeloid Malignancies | Page 13

While retinoids such as tretinoin are the backbone of treatment of patients with acute promyelocytic leukemia (APL), a subset of patients with non-APL, AML, or MDS will respond to treatment with retinoic acid derivatives. Tamibarotene is a retinoid analogue licensed for treatment of APL in Japan. In this open-label, single-group assign- ment study, patients who have a gene expression signature (RARA or IRF8 genes) that preclinical testing has suggested indicates a higher likelihood of response to tamibarotene will be eligible for treatment with this drug. A Safety and Tolerability Study of Crenolanib in Combination With Chemotherapy in Newly Diagnosed AML Patients With FLT3 Mutations (NCT02283177) estimated study completion date: January 2019 estimated enrollment: 48 sponsor: Arog Pharmaceuticals, Inc. In the Alliance Cooperative Group-led RATIFY trial, the combination of conventional anthracycline/cytarabine induction and cytarabine consol- idation with the multi-kinase inhibitor midostaurin improved survival in patients with FLT3-mutated AML, compared with chemotherapy without midostaurin. This non-randomized, parallel-assignment, open-label study tests a novel FLT3/PDGFR inhibitor, crenolanib, given sequentially during standard induction and consolidation in patients with newly diagnosed AML with FLT3-activating mutations. Crenolanib inhibits both wild-type FLT3 and type 1 mutations. SPOTLIGHT: The Beat AML Master Trial A Master Protocol for Biomarker-Based Treatment of AML (NCT03013998) estimated study completion date: December 2021 estimated enrollment: 500 sponsor: The Leukemia & Lymphoma Society In October 2016, The Leukemia & Lymphoma Society (LLS) announced the Beat AML Master Trial – the latest effort in the society’s Beat AML initiative, which launched in 2013 to unite researchers, patients, pharmaceutical companies, and physicians to analyze the genomic causes of AML and identify new treatment options. This trial will enroll older patients (≥60 years of age) with newly diagnosed, untreated AML who will undergo genomic testing to assign them to a treatment strategy. The primary endpoint is clinical response to each novel therapy, and the trial will also include patient-reported outcomes. Enrollment comprises three phases: • • PHASE I TRIALS Dose Escalation of OXi4503 as Single Agent and Combination With Cytarabine w/ Subsequent Phase II Cohorts for AML and MDS (NCT02576301) estimated study completion date: October 2020 estimated enrollment: 105 sponsor: Mateon Therapeutics The first phase of this randomized, open-label, single-group assign- ment study will investigate the maximum tolerated dose of OXi4503 (combretastatin A1 di-phosphate), a vascular disrupting agent, as a single agent and in combination with intermediate-dose cytarabine in subjects with relapsed/refractory AML or MDS. The second phase will investigate the overall response rate of OXi4503 in combination with intermediate-dose cytarabine in two groups: Patients with MDS after failure of one prior HMA and patients with relapsed and refractory AML after treatment failure of up to one prior chemotherapy regimen. Study to Determine Safety, Pharmacokinetics and Efficacy of GMI- 1271 in Combination With Chemotherapy in AML (NCT02306291) estimated study completion date: December 2018 estimated enrollment: 102 sponsor: GlycoMimetics, Inc. This non-randomized, single-group assignment, open-label study will evaluate the safety and efficacy of GMI-1271, in combination with a standard 7+3 regimen, for the treatment of patients with AML. GMI- 1271 blocks the adhesion molecule E-selectin from binding with AML cells to disrupt mechanisms of leukemic cell resistance within the bone marrow microenvironment. In June 2016, the FDA granted fast-track designation to GMI-1271. • Patients will undergo a bone marrow biopsy, followed by genomic screening within a 7-day period. Based on their genetic profile, patients will be assigned to receive personalized investigational therapy. Unlike other clinical trials where one drug or drug combination is studied, this trial will begin with four different treatments. Combi- nation regimens may also be studied during the trial. If a patient does not have a genetic marker that would place him or her in a specific treatment cohort, then he or she will be offered a different investigational broad-acting AML agent. There will be a follow-up period of ≥28 days after treatment is complete. The total duration may be 1 to 3 years. Enrollment has already begun at the five participating centers: Memorial Sloan Kettering Cancer Center in New York, New York; The Ohio State University Comprehensive Cancer Center in Columbus, Ohio; Oregon Health & Science University's Knight Cancer Institute in Portland, Oregon; and Dana-Farber Cancer Institute and Massachu- setts General Hospital Cancer Center in Boston, Massachusetts. Six additional clinical sites are set to begin enrollment this year, and the trial will eventually expand to between 15 and 20 sites with up to 10 different treatment arms. Trial participants will be treated with one of four investigational drugs (samalizumab, BI 836858, enasidenib, or entospletinib) provided by participating pharmaceu- tical companies. The American Society of Hematology (ASH) and LLS have teamed up to educate and raise awareness about the need for new treatments for AML. At the 2016 ASH Annual Meeting, the trial’s three lead investigators, Brian Druker, MD, John Byrd, MD, and Ross Levine, MD, discussed the rationale of the Beat AML Master Trial. “This trial is about matching the right patients with the right drug,” Dr. Druker said. ”It’s time to stop treating AML like one disease; it is multiple blood cancers, each driven by different genetic mutations.” “We have seen too few drugs achieve approval for AML, and, even when drugs are approved, getting them into the clinic takes too long and these agents generally are not tailored to a patient’s genotype,” Dr. Levine said. “We hope this trial increases the speed in which we can bring new drugs to patients and provides a template for new master trials and drug development in a wider spectrum of human cancers.” May 2017 11