Selected by David Steensma, MD

Ruxolitinib and Pracinostat Combination Therapy for Patients With Myelofibrosis (NCT02267278)

  • Study Design: Open-label, single-group assignment safety/efficacy study
  • Study Start Date: January 2015
  • Estimated Study Completion Date: January 2018
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 25
  • Sponsor: MD Anderson Cancer Center, MEI Pharma

Ruxolitinib is an established palliative therapy for patients with myelofibrosis and offers the possibility of improvement in splenomegaly and constitutional symptoms.  In vitro analysis has shown that there is synergy between JAK2 inhibitors (like ruxolitinib) and deacetylase inhibitors (like pracinostat). Pracinostat has shown activity in myelodysplastic syndrome when used in combination with hypomethylating agents. This trial is an example of one of several ongoing trials evaluating combination therapy regimens with JAK2 inhibitors in myelofibrosis.

Phase 2 Dose-Ranging Trial of Ponatinib in Patients With Refractory, Chronic-Phase Chronic Myeloid Leukemia

  • Study Design: Multicenter, dose-finding study
  • Study Start Date: Mid-2015
  • Study Status: Not yet recruiting participants
  • Estimated Enrollment: 450
  • Sponsor: Ariad Pharmaceuticals

Ponatinib is approved for chronic myeloid leukemia (CML) or Ph+ acute lymphocytic leukemia (ALL) with either T315I mutation, or patients for whom all other tyrosine kinase inhibitor (TKI) drugs have failed. When the drug was originally approved by the FDA in 2013, it was approved at 45 mg/day, which may be too high for many patients. The drug was briefly taken off the market in late 2013 in the United States due to a higher-than-anticipated rate of cardiovascular events, including vascular occlusion. Now when we start patients on ponatinib we usually do so at a dose of 15 or 30 mg/day. This study will enroll approximately 450 patients at three different starting doses of ponatinib in order to understand whether lower doses might be safer or might differ in effectiveness from higher doses.

Selected by Alice Ma, MD

Study to Assess Safety and Impact of SelG1 With or Without Hydroxyurea Therapy in Sickle Cell Disease Patients With Pain Crises (SUSTAIN) (NCT01895361)

  • Study Design: Randomized, double-blind parallel assignment study
  • Study Start Date: July 2013
  • Estimated Study Completion Date: August 2015
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 174
  • Sponsor: Selexys Pharmaceuticals Corporation

Pharmacologic prevention and treatment of sickle cell crises has relied on a single agent—hydroxyurea—for many years.  However, a recent spate of promising new agents is now in clinical trials. Therapies are now aimed at blocking adhesion receptors, increasing fetal hemoglobin, altering the oxygen affinity of hemoglobin S, blocking ischemia/reperfusion injury, and altering the arginine metabolome. The SUSTAIN trial evaluates SelG1, an inhibitor of p-selectin; in preclinical studies, inhibition of p-selectin prevented vaso-occlusion by blocking cell-cell interactions. Based on the safety demonstrated by SelG1 in a phase 1 trial in normal subjects, this phase 2 trial is underway to determine if the drug with or without hydroxyurea impacts the incidence and severity of painful vaso-occlusive crises.

Efficacy and Safety of Rivipansel (GMI-1070) in the Treatment of Vaso-Occlusive Crisis in Hospitalized Subjects With Sickle Cell Disease (NCT02187003)

  • Study Design: Randomized, double-blind, parallel assignment safety/efficacy study
  • Study Start Date: June 2015
  • Estimated Study Completion Date: July 2018
  • Study Status: Not yet open for recruitment
  • Estimated Enrollment: 350
  • Sponsor: Pfizer

Rivipansel is a synthetic glycomimetic molecule, which was rationally designed as a pan-selectin inhibitor that will inhibit all three selectin types. A phase 2 randomized, double-blind study in hospitalized patients with sickle cell disease experiencing veno-occlusive crisis (VOC) found that rivipansel reduced the time to reach resolution of VOC, length of hospital stay, and use of opioid analgesics for pain management. This follow-up phase 3, multicenter, randomized, double-blind, placebo-controlled clinical study will evaluate the safety and efficacy of rivipansel in patients experiencing a pain crisis necessitating hospitalization.

Selected by Keith Stewart, MBChB, MBA

Phase III Study of Lenalidomide and Dexamethasone With or Without Elotuzumab to Treat Relapsed or Refractory Multiple Myeloma (ELOQUENT – 2) (NCT01239797)

  • Study Design: Randomized, open-label, parallel assignment efficacy study
  • Study Start Date: March 2011
  • Estimated Study Completion Date: March 2018
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 458
  • Sponsor: Bristol-Myers Squibb, AbbVie

The phase 3 ELOQUENT – 2 study has completed accrual and results are expected this year. This trial builds on impressive response rates and longer progression-free survival in the phase 2 trial of patients treated with lenalidomide plus weekly dexamethasone in combination with the monoclonal antibody elotuzumab. Elotuzumab targets the cell surface receptor SLAMF7, which is prominently expressed on plasma cells in patients with myeloma. The combination of these three drugs is being tested against standard-of-care in relapsed myeloma and may advance care in the event of a positive trial by introducing the first monoclonal antibody to myeloma therapy.

A Phase 3 Study Comparing Oral Ixazomib Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Relapsed and/or Refractory Multiple Myeloma (NCT01564537)

  • Study Design: Randomized, double-blind, parallel assignment safety/efficacy study
  • Study Start Date: August 2012
  • Estimated Study Completion Date: May 2019
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 703
  • Sponsor: Millennium Pharmaceuticals, Inc.

This is another important phase 3 trial in myeloma comparing the use of ixazomib, the first oral proteasome inhibitor, in combination with lenalidomide and weekly dexamethasone with the standard of care. Once again, this three-drug regimen is first being studied in the relapsed/refractory multiple myeloma population, but trials in newly diagnosed patients are also underway. A positive study would launch the first oral combination therapy incorporating the most active targeted pathways in this disease – with the potential to dramatically improve convenience for patients.