CAR T Cells in AML, Preventing VTE in Cancer Patients, and more

LEUKEMIA

David Steensma, MD
Dana-Farber Cancer Institute

Phase 1b Acute Myelogenous Leukemia (AML) Study with ABT-199 + Decitabine or Azacitidine (Chemo Combo) (NCT02203773)

  • Study Design: Phase Ib, non-randomized, open-label safety/efficacy study
  • Study Start Date: November 2014
  • Estimated Study Completion Date: May 2017
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 100
  • Sponsor: AbbVie

This study is evaluating the safety of orally administered ABT-199 (venetoclax) in combination with decitabine or azacitidine and the preliminary efficacy of one of these combinations in patients 65 years old or older with AML. DNA hypomethylating agents such as decitabine and azacitidine are commonly used to treat older, frailer patients who decline intensive chemotherapy. ABT-199, a potent and selective BCL-2 inhibitor, lowers the apoptosis threshold of neoplastic cells and sensitizes cells to cytotoxic agents. It has striking activity as a single agent in lymphoproliferative disorders, but the activity as a monotherapy for AML is limited. However, combining ABT-199 with chemotherapy may be synergistic in AML and may be enough to give low-intensity therapy such as decitabine or azacitidine in combination with ABT-199 in order to “push cells over the edge” and into apoptosis, which would augment response rate without requiring intensive chemotherapy.

Safety Study of Chimeric Antigen Receptor Modified T cells Targeting NKG2D-Ligands (NCT02203825)

  • Study Design: Phase I, open-label, single-group safety study
  • Study Start Date: March 2015
  • Estimated Study Completion Date: March 2019
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 24
  • Sponsor: Celdara Medical, LLC

This trial is evaluating chimeric-antigen receptor (CAR) T cells (CM-CS1 T cells) and the safety and feasibility of administering a single intravenous dose of CM-CS1 CAR T cells to patients with AML, myelodysplastic syndrome (MDS)–refractory anemia with excess blasts, and multiple myeloma (MM). Bioengineered CAR T cells have shown striking activity in CD19+ lymphoid neoplasms, but it has proven difficult to define a suitable target for CAR T cells in myeloid neoplasms that do not result in profound, durable neutropenia. NKG2D ligands are expressed by tumor cells in some patients with AML and other hematologic neoplasms and may be a potential target for cell-based immunotherapy. In this study, patients with AML or MDS with excess blasts for whom no standard therapy exists are being administered autologous CAR T cells engineered to recognize NKG2D ligands. Patients with relapsed and/or refractory MM are also eligible.

SGI-110 in Adults with Untreated Acute Myeloid Leukemia (AML), Not Considered Candidates for Intensive Remission Induction (NCT02348489)

  • Study Design: Phase III, randomized, open-label, parallel-assignment safety/efficacy study
  • Study Start Date: March 2015
  • Estimated Study Completion Date: December 2017
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 800
  • Sponsor: Astex Pharmaceuticals

This study is comparing the efficacy and safety between SGI-110 (guadecitabine) and treatment choice in adults with previously untreated AML who are not considered candidates for intensive remission induction chemotherapy. SGI-110 is a hypomethylating agent that is a dinucleotide combination of decitabine and deoxyguanosine; it appears to have improved pharmacokinetic and pharmacodynamic behavior compared with decitabine. In this study, 800 patients (age 75 years old or older) with newly diagnosed AML or those with organ dysfunction or poor performance status, will be randomized to receive SGI-110, decitabine, or azacitidine. The primary endpoint is survival.


BLEEDING DISORDERS

Alice Ma, MD
University of North Carolina School of Medicine

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

  • Study Design: Phase III, 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

This superiority study is comparing the efficacy and safety of rivaroxaban with placebo for primary prophylaxis of venous thromboembolism (VTE) in ambulatory adult participants with various cancer types who are scheduled to initiate systemic cancer therapy. The study consists of three phases: 1) screening phase (14 days); 2) double-blind treatment phase (180 days); and 3) follow-up phase (30 days). The duration of participation in the study for each participant is approximately 32 weeks.

The purpose of this study is to demonstrate that rivaroxaban is superior to placebo for reducing the risk of the primary composite outcome (symptomatic lower-extremity proximal DVT, asymptomatic lower-extremity proximal DVT, symptomatic upper-extremity DVT, symptomatic non-fatal PE, incidental PE, and VTE-related death) in adults who are at high risk for developing a VTE.

The primary endpoint is time from randomization to first occurrence of the composite outcome. The primary safety objective is to assess the major bleeding events as defined by the International Society on Thrombosis and Hemostasis.

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

  • Study Design: Phase III, 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: Eastern McMaster University

This study will assess a new diagnostic management strategy for suspected deep-vein thrombosis (DVT) in outpatients. The strategy is 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 because more patients will have DVT excluded by combinations of Clinical Pretest Probability and D-dimer results on the day of presentation. In those who still need an ultrasound, a repeat ultrasound conducted a 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 determined by a very low rate of proximal DVT or pulmonary embolism (PE) during 90 days of follow-up in patients who had anticoagulant therapy withheld in response to negative diagnostic testing.

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

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

Cancer patients have an increased risk of developing blood clots in the veins compared with non-cancer patients. The patients who do develop blood clots can face reduced life expectancy, delayed cancer treatment, and decreased quality of life. Prevention is the most effective way to decrease the complications associated with blood clots in the veins. Although previous clinical trials have shown some benefit to using medication to prevent blood clots in the veins in ambulatory cancer patients, these studies have been inconclusive in demonstrating that existing blood thinners significantly reduce the rate of blood clots in cancer patients. One possible explanation relates to the fact that these studies have included a large proportion of cancer patients who are at low risk for developing blood clots in the veins. The trial aims to identify patients who are at a high risk for developing blood clots by using a validated tool at the time of their cancer diagnosis. The identified high-risk cancer patients will then be asked to participate in a trial to test the safety and efficacy of apixaban. The primary outcome is a first episode of objectively documented, symptomatic, or asymptomatic VTE. Secondary outcomes include the rate of adverse events.

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