APEX, STORM, and more

LEUKEMIA

Selected by David Steensma, MD

A Study of the Safety and Pharmacokinetics of RO6839921, an MDM2 Antagonist, in Patients with Advanced Cancers, including Acute Myeloid Leukemia (NCT02098967)

  • Study Design: Non-randomized, open-label, parallel-assignment safety study
  • Study Start Date: April 2014
  • Estimated Study Completion Date: September 2015
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 90
  • Sponsor: Hoffman-La Roche

While the tumor suppressor p53 is an attractive cancer target (since it is inactivated in many neoplasms, including a subset of AML), thus far no therapy effectively targets p53. One mechanism of p53 inactivation is suppression by the MDM2 protein. Small molecules that block the interaction of MDM2 with p53 can reactivate the p53 function and may be a useful strategy for the treatment of cancers retaining wild-type p53. This approach is not expected to be active if p53 itself is genetically altered (i.e., mutated or deleted).

Study of Azacitidine With or Without Birinapant in Subjects With MDS or CMMoL (NCT02147873)

  • Study Design: Randomized, parallel-assignment, double-blind safety/efficacy study
  • Study Start Date: June 2014
  • Estimated Study Completion Date: December 2016
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 158
  • Sponsor: TetraLogic Pharmaceuticals

Combination therapies in the myelodysplastic syndromes (MDS) have thus far been disappointing, despite a number of randomized trials that have added a deactylase inhibitor (e.g., entinostat in ECOG E1905, vorinostat in the U.S./Canadian Intergroup S1117 study, pracinostat in an MEI Pharma-sponsored trial, and valproic acid in a French study) or lenalidomide (S1117 and an Australian trial) to azacitidine. Birinapant is an SMAC mimetic and inhibitor of apopotosis (IAP)–antagonist that inhibits the activity of several IAPs, such as X chromosome-linked IAP (XIAP) and cellular IAPs 1 and 2 (cIAP1 and cIAP2). Since IAPs protect neoplastic cells from apoptosis, birinapant may restore and promote the induction of apoptosis through apoptotic signaling pathways in cancer cells. Other than the availability of azacitidine and its known effectiveness in MDS and chronic myelomonocytic leukemia (CMMoL), there is no specific rationale for expecting a synergistic effect with this combination.


BLEEDING DISORDERS

Selected by Alice Ma, MD

We still aren’t sure exactly how long to treat a patient with symptomatic venous thrombosis, which agents to use, or how to best prevent venous thromboembolism (VTE). Here is a selection of trials investigating these questions.

Reduced-Dosed Rivaroxaban in the Long-Term Prevention of Recurrent Symptomatic VTE (NCT02064439)

  • Study Design: Randomized, parallel-assignment, double-blind safety/efficacy study
  • Study Start Date: March 2014
  • Estimated Study Completion Date: November 2016
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 2,850
  • Sponsor: Bayer

This is a multicenter, randomized, double-blind, event-driven, superiority study for efficacy. Patients with confirmed symptomatic deep-vein thrombosis (DVT) or pulmonary embolism (PE) who completed six or 12 months of treatment of anticoagulation are eligible for this trial. Patients will be randomized to 20 mg rivaroxaban, 10 mg rivaroxaban, or 100 mg aspirin for 12 months, and then they will be followed for development of symptomatic, recurrent VTE, or major bleeding.

Acute Medically Ill VTE Prevention With Extended Duration Betrixaban Study (The APEX Study) (NCT01583218)

  • Study Design: Randomized, parallel-assignment, double-blind safety/efficacy study
  • Study Start Date: March 2012
  • Estimated Study Completion Date: September 2015
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 6,850
  • Sponsor: Portola Pharmaceuticals

This study will evaluate whether extended prophylaxis with oral betrixaban can prevent blood clots in the leg and lung that may occur in patients who are hospitalized for an acute medical illness. Efficacy and safety of the study drug will be compared with standard-of-care enoxaparin.

Superficial Vein Thrombosis (SVT) Treated With Rivaroxaban Versus Fondaparinux (NCT01499953)

  • Study Design: Randomized, parallel-assignment, open-label safety/efficacy study
  • Study Start Date: April 2012
  • Estimated Study Completion Date: March 2017
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 506
  • Sponsor: GWT-TUD GmbH

This randomized, open-label study will evaluate the efficacy and safety of rivaroxaban versus fondaparinux in the treatment of superficial vein thrombosis (SVT). Patients will be followed for occurrence of major bleeding, rate of major venous thromboembolism, and death from any cause.


LYMPHOMA & MYELOMA

Selected by Keith Stewart, MBChB, MBA

A Phase 1-2 Multi-Center Study Evaluating KTE-C19 in Subjects With Refractory Aggressive Non-Hodgkin Lymphoma (NHL) (NCT02348216)

  • Study design: Non-randomized, single-group assignment, open-label safety/efficacy study
  • Study start date: January 2015
  • Estimated study completion date: March 2017
  • Study status: Currently recruiting participants
  • Estimated enrollment: 124
  • Sponsor: Kite Pharma, Inc.

Phase IIa Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCRz and 4-Signaling Domains in Patients With Chemotherapy Relapsed or Refractory CD19+ Lymphomas (NCT02030834)

  • Study Design: Single cohort, open-label pilot study
  • Study Start Date: January 2014
  • Estimated Study Completion Date: July 2015
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 55
  • Sponsor: Abramson Cancer Center of the University of Pennsylvania

These are two in a number of early-phase clinical trials examining the use of autologous T cells engineered with chimeric antigen receptor (CAR) engineered to express CD19 in conjunction with T-cell receptor signaling domains. Early success in childhood acute lymphocytic leukemia has provoked extensive excitement about the potential of this approach in other CD19-expressing B-cell malignancies.

Phase 2b Open-Label Single-Arm Study With KPT-330 + Dexamethasone in Patients w/ Quad-Refractory Multiple Myeloma (STORM) (NCT02336815)

  • Study Design: Single cohort, open-label pilot study
  • Study Start Date: May 2015
  • Estimated Study Completion Date: November 2016
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 80
  • Sponsor: Karyopharm Therapeutics, Inc.

This is a potential registration trial of selinexor, a novel small molecule inhibitor targeting the nuclear transport protein exportin (XPO-1, also known as CRM-1) in multiple myeloma. Early reports of single-agent activity, as well as a 60 percent response rate in a study of 10 refractory patients who received selinexor plus dexamethasone, prompted the design of this trial, which will look at the safety and efficacy of selinexor in heavily treated patients with unmet medical need.

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