Clinical Trial: Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Phase 2 Study of Brentuximab Vedotin Plus Cyclophosphamide, Doxorubicin, Etoposide, and Prednisone (CHEP-BV) Followed by BV Consolidation in Patients With CD30-Positive Peripheral T-Cell Lymphomas

Brief Summary: This phase II trial studies the side effects and how well brentuximab vedotin and combination chemotherapy work in treating patients with CD30-positive peripheral T-cell lymphoma. Monoclonal antibodies, such as brentuximab vedotin may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, etoposide, and prednisone work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving brentuximab vedotin and combination chemotherapy may work better in treating patients with CD30-positive peripheral T-cell lymphoma.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Assess the safety and tolerability of cyclophosphamide, doxorubicin, etoposide, prednisone, and brentuximab vedotin (CHEP-BV), as induction therapy in patients with CD30-positive peripheral T-cell lymphoma (PTCL). (Safety lead-in) II. Assess the anti-lymphoma activity of CHEP-BV as induction treatment in patients with CD30-positive PTCL. (Phase 2)

SECONDARY OBJECTIVES:

I. Describe outcomes of CD30-positive PTCL patients who go on to receive BV consolidation therapy post CHEP-BV induction with/without autologous hematopoietic cell transplantation.

TERTIARY OBJECTIVES:

I. Explore the rate of minimal residual disease (MRD) negativity (as assessed by next-generation sequencing) and MRD kinetics after CHEP-BV and BV consolidation therapy in CD30-positive PTCL.

II. Explore the possible association between outcome after study treatment and CD30 expression, gene expression profiles (GEP), and genetic mutations as measured in PTCL tumor samples.

OUTLINE:

INDUCTION: Patients receive cyclophosphamide intravenously (IV) and doxorubicin IV on day 1, etoposide IV on days 1-3, and prednisone orally (PO) on days 1-5. Patients also receive brentuximab vedotin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Between 30-60 days post-consolidative autologous stem cell therapy or after completing induction course 6, patients with objective response (compete response or
Sponsor: City of Hope Medical Center

Current Primary Outcome: Complete response (CR) rate after CHEP-BV induction therapy [ Time Frame: Up to 1 year ]

Will be estimated by the proportion of evaluable patients achieving CR after CHEP-BV induction therapy, along with the 95% exact binomial confidence interval.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • CR rate after BV consolidation therapy [ Time Frame: Up to 1 year ]
    Will be estimated by the proportion of evaluable patients achieving CR after BV consolidation therapy, along with the 95% exact binomial confidence interval.
  • Incidence of adverse events after CHEP-BV induction therapy [ Time Frame: Up to 1 year ]
    Will be summarized by type (organ affected or laboratory determination such as absolute neutrophil count), severity (by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.03 and nadir or maximum values for lab measures), date of onset, duration, reversibility, and attribution.
  • Incidence of adverse events of BV consolidation after CHEP-BV induction therapy and ASCT [ Time Frame: Up to 1 year ]
    Will be summarized by type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE version 4.03 and nadir or maximum values for lab measures), date of onset, duration, reversibility, and attribution.
  • Incidence of adverse events of BV consolidation after CHEP-BV induction therapy without ASCT [ Time Frame: Up to 1 year ]
    Will be summarized by type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE version 4.03 and nadir or maximum values for lab measures), date of onset, duration, reversibility, and attribution.
  • Overall response rate after induction therapy [ Time Frame: Up to 1 year ]
    Will be estimated by the proportion of evaluable patients achieving overall response rate after induction therapy. Will be estimated along with the 95% exact binomial confidence interval.
  • Overall survival [ Time Frame: The time from enrollment to death from any cause assessed up to 1 year ]
    Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error.
  • Progression-free survival [ Time Frame: The time from enrollment to the first observation of disease relapse/progression or death from any cause, whichever occurs first assessed up to 1 year ]
    Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error.


Original Secondary Outcome: Same as current

Information By: City of Hope Medical Center

Dates:
Date Received: April 10, 2017
Date Started: June 2017
Date Completion: June 2019
Last Updated: April 10, 2017
Last Verified: April 2017