Vadastuximab Talirine in Higher-Risk MDS, Low-Dose Rituximab for Acquired TTP, and more

ASH Clinical News’ Associate Editors select clinical trials to keep an eye on in leukemia, bleeding disorders, and lymphoma & myeloma.

LEUKEMIA

David Steensma, MD
Dana-Farber Cancer Institute

Study of Vadastuximab Talirine (SGN-CD33A; 33A) in Combination With Azacitidine in Patients With Previously Untreated Higher Risk MDS (NCT02706899)

  • Study Design: Randomized, parallel-assignment study
  • Study Start Date: February 2016
  • Estimated Study Completion Date: June 2019
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 130
  • Sponsor: Seattle Genetics, Inc.

Vadastuximab is an anti-CD33 antibody-drug conjugate with activity in acute myeloid leukemia (AML). Frequently, immature cells in patients with myelodysplastic syndromes (MDS) express CD33. This study explores use of vadastuximab in combination with azacitidine, a U.S. Food and Drug Administration (FDA)-approved DNA hypomethylating agent that extends survival in higher-risk MDS, compared with conventional care.

Study to Determine and Evaluate a Safe and Tolerated Dose of HDM201 in Patients With Selected Advanced Tumors That Are TP53wt (NCT02143635)

  • Study Design: Non-randomized, parallel-assignment study
  • Study Start Date: July 2014
  • Estimated Study Completion Date: November 2017
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 176
  • Sponsor: Novartis Pharmaceuticals

HDM201 is an oral agent that inhibits binding of the protein human double minute 2 homolog (HDM2) to the transcriptional activation domain of the tumor suppressor protein p53. HDM2 is frequently overexpressed in AML blasts and other cancer cells. By inhibiting HDM2, p53 signaling may be restored, which would be expected to result in p53-mediated induction of tumor cell apoptosis.

BLEEDING DISORDERS

Alice Ma, MD
University of North Carolina School of Medicine

Thrombocytopenic purpura (TTP) is a disease that is nearly universally fatal without therapy. The mainstay of therapy is plasma exchange, but many patients die despite treatment and early diagnosis. Additionally, relapse is common. Several studies are investigating modalities to reduce relapse rates.

Adjuvant Low Dose Rituximab for Acquired TTP With Severe ADAMTS13 Deficiency (NCT01554514)

  • Study Design: Single-group assignment, open-label study
  • Study Start Date: August 2012
  • Estimated Study Completion Date: December 2017
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 20
  • Sponsor: National Heart, Lung, and Blood Institute

This is a pilot safety/efficacy study of adjuvant low-dose rituximab (100 mg/week x 4 doses) plus standard plasma exchange and corticosteroids for patients with TTP and severe ADAMTS13 deficiency. To test the hypothesis that adjuvant low-dose rituximab may decrease the incidence of TTP exacerbations or refractory disease, results for study subjects will be compared to historical controls treated initially with plasma exchange and corticosteroids. A novel ADAMTS13 assay will be used to assess the prognostic value of ADAMTS13.

Safety Study of Danazol With Plasma Exchange and Steroids for the Treatment of Thrombotic Thrombocytopenic Purpura (NCT00953771)

  • Study Design: Single-group assignment, open-label study
  • Study Start Date: October 2008
  • Estimated Study Completion Date: December 2020
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 25
  • Sponsor: Beth Israel Medical Center

Danazol is a synthetic steroid hormone that structurally resembles naturally occurring androgens. Danazol has been shown to be effective in treating blood disorders with low platelet counts, but is not yet approved by the FDA for TTP. In an early study, danazol plus plasma exchange decreased the number of plasma exchanges required by approximately 80 percent in patients with TTP, but the mechanism is not yet clear.

LYMPHOMA & MYELOMA

Keith Stewart, MBChB, MBA
Mayo Clinic, Arizona

Study Comparing Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone (D-RVd) Versus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Subjects With Newly Diagnosed Multiple Myeloma (NCT02874742)

  • Study Design: Randomized, parallel-assignment study
  • Study Start Date: August 2016
  • Estimated Study Completion Date: January 2020
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 216
  • Sponsor: Janssen Research & Development, LLC

Daratumumab was recently approved for relapsed multiple myeloma (MM) patients. This trial will set the stage for use of this drug in combination with a proteosome inhibitor in newly diagnosed patients. The purpose of this study is to determine whether adding daratumumab to lenalidomide-bortezomib-dexamethasone (RVd) will increase the rate of stringent complete response after autologous hematopoietic cell transplantation, compared with RVd alone.

A Safety Study to Determine Dose and Tolerability of CC-220 Monotherapy and in Combination With Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma (NCT02773030)

  • Study Design: Randomized, parallel-assignment, open-label study
  • Study Start Date: October 2016
  • Estimated Study Completion Date: June 2020
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 106
  • Sponsor: Celgene Corporation

CC-220 is a cereblon-binding immunomodulator with in vitro potency more than 100 times that of pomalidomide. This multicenter, international, open-label, phase Ib/IIa dose-escalation study will determine the maximum tolerated dose of CC-220 when administered as monotherapy, as well as in combination with dexamethasone. Once the recommended phase II dose for each drug is determined, part two of the study will evaluate the safety and preliminary efficacy of combination treatment with CC-220 and dexamethasone.

Study of Venetoclax in Combination With Carfilzomib and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (NCT02899052)

  • Study Design: Single-group assignment, open-label study
  • Study Start Date: December 2016
  • Estimated Study Completion Date: August 2020
  • Study Status: Currently recruiting participants
  • Estimated Enrollment: 40
  • Sponsor: AbbVie

Venetoclax has shown activity in clinical trials, especially for patients with t(11;14) MM. The agent also has been effective in a broader spectrum of patients when used in combination with bortezomib. This is a phase II, open-label, dose-escalation study to evaluate the safety and efficacy of venetoclax in combination with carfilzomib-dexamethasone in participants with relapsed or refractory MM who have received one to three prior lines of therapy.

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