4D Study, Rivaroxaban, and more

BLEEDING DISORDERS

Alice Ma, MD
University of North Carolina School of Medicine

This month’s benign hematology section focuses on the prevention and management of venous thromboembolism (VTE).

The Designer D-dimer Deep-Vein Thrombosis Diagnosis (4D) Study (NCT02038530)

  • Study Design: Prospective, observational cohort study
  • Study Start Date: February 2014
  • Estimated Study Completion Date: December 2016
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 1,500
  • Sponsor: McMaster University

This study will assess a new diagnostic management strategy for suspected deep-vein thrombosis (DVT) in outpatients 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 for two reasons: More patients will have DVT excluded by combinations of clinical pretest probability and D-dimer results on the day of presentation and, in those who still need an ultrasound, a repeat ultrasound one 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 established by demonstrating a very low rate of proximal DVT or pulmonary embolism during 90-day follow-up in patients who had anticoagulant therapy withheld in response to negative diagnostic testing.

A Study to Evaluate the Efficacy and Safety of Rivaroxaban Venous Thromboembolism (VTE) Prophylaxis in Ambulatory Cancer Participants (NCT02555878)

  • Study Design: Randomized, double-blind, parallel-assignment 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

The purpose of this study is to demonstrate that rivaroxaban is superior to placebo in reducing the risk of the primary composite outcome (time from randomization to first occurrence of objectively confirmed symptomatic and symptomatic lower-extremity proximal DVT, symptomatic upper-extremity DVT, symptomatic non-fatal PE, incidental PE, and VTE-related death) in ambulatory adult participants with various cancer types receiving systemic cancer therapy who are at high risk for developing a VTE.

Apixaban for the Prevention of Venous Thromboembolism in Cancer Patients (AVERT) (NCT02048865)

  • Study Design: Randomized, double-blind, parallel-assignment safety/efficacy study
  • Study Start Date: January 2014
  • Estimated Study Completion Date: June 2017
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 574
  • Sponsor: Ottawa Hospital Research Institute

Previous clinical trials reporting on the use of thromboprophylaxis in ambulatory cancer patients have not been conclusive, potentially due to the inclusion of cancer patients at low risk for VTE. This study will identify a group of cancer patients at high risk for VTE and test the ability of apixaban to prevent clots.


LEUKEMIA

David Steensma, MD
Dana-Farber Cancer Institute

The Phase III MEDALIST Study

  • Study Design: Double-blind, randomized, placebo-controlled safety/efficacy study
  • Study Start Date: November 2015
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 210
  • Sponsor: Acceleron Pharma Inc.

The MEDALIST study, a phase III randomized, multicenter trial will compare luspatercept versus placebo in 210 patients with IPSS-R very-low to intermediate-risk myelodysplastic syndromes (MDS) with anemia who are ineligible for erythropoiesis-stimulating agents or did not respond to such therapy. The primary endpoint is the proportion of patients who become red blood cell transfusion-independent (≥8 weeks) during the first 24 weeks of the study. Luspatercept (formerly ACE-536) is an activin 2 receptor ligand trap that augments GDF11 signaling, especially in patients with ring sideroblasts and SF3B1 mutations. This is a needy group of patients without good therapeutic options.

The Life After Stopping Tyrosine Kinase Inhibitors Study (The LAST Study) (NCT02269267)

  • Study Design: Open-label, prospective, single-group assignment longitudinal study
  • Study Start Date: December 2014
  • Estimated Study Completion Date: December 2021
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 173
  • Sponsor: Medical College of Wisconsin

Many patients with chronic-phase chronic myeloid leukemia (CML) want to stop taking their prescribed tyrosine kinase inhibitor (TKI; imatinib, dasatinib, nilotinib, or bosutinib), but we know that some patients have disease recurrence within the first few months after doing so. The LAST Study will help us understand the decision process and relapse risk. The study will closely monitor patients using standard RQ-PCR testing for molecular recurrence, testing participants monthly for six months, then every other month until 24 months, and then quarterly until 36 months. Concurrently, the study will assess a wide range of patient-reported outcomes before stopping TKIs and after discontinuation in conjunction with PCR testing, though at fewer time points. Patients who have molecular CML recurrence based on RQ-PCR will restart imatinib, dasatinib, nilotinib, or bosutinib and will continue to be monitored for disease status and patient-reported health status until the end of the study.


LYMPHOMA & MYELOMA

Keith Stewart, MBChB, MBA
Mayo Clinic, Arizona

Bortezomib or Carfilzomib With Lenalidomide and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma (NCT01863550)

  • Study Design: Randomized, open-label, parallel-assignment efficacy study
  • Study Start Date: November 2013
  • Estimated Study Completion Date: May 2016
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 756
  • Sponsor: Eastern Cooperative Oncology Group

This randomized phase III trial will study the combination of bortezomib, lenalidomide, and dexamethasone to see how well it works compared with carfilzomib, lenalidomide, and dexamethasone in treating patients with newly diagnosed multiple myeloma (MM). The study is also looking at long-term survival (up to 15 years) in these patients.

Two KEYNOTE trials are evaluating the efficacy of adding the anti-PD-1 antibody pembrolizumab to standard treatment regimens in patients with relapsed/refractory and treatment-naïve MM, respectively. KEYNOTE-183 will evaluate the efficacy of pomalidomide and low-dose dexamethasone with or without pembrolizumab in patients with relapsed/refractory MM who had undergone at least two lines of prior treatment, including an immunomodulatory drug and proteasome inhibitor alone or in combination. KEYNOTE-185 will compare the efficacy of lenalidomide and low-dose dexamethasone with and without pembrolizumab, specifically looking at progression-free survival in participants with newly diagnosed MM who are ineligible for autologous hematopoietic cell transplant.

Study of Pomalidomide and Low-Dose Dexamethasone With or Without Pembrolizumab (MK-3475) in Refractory or Relapsed and Refractory Multiple Myeloma (rrMM) (MK-3475-183/KEYNOTE-183) (NCT02576977)

Study of Lenalidomide and Dexamethasone With or Without Pembrolizumab (MK-3475) in Participants With Newly Diagnosed Treatment Naive Multiple Myeloma (MK-3475-185/KEYNOTE-185) (NCT02579863)

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