Clinical Trial: Brentuximab Vedotin or Crizotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II-IV Anaplastic Large Cell Lymphoma

Study Status: Suspended
Recruit Status: Suspended
Study Type: Interventional

Official Title: A Randomized Phase 2 Trial of Brentuximab Vedotin (SGN35, NSC# 749710), or Crizotinib (NSC#749005, Commercially Labeled) in Combination With Chemotherapy for Newly Diagnosed Patients With

Brief Summary: This partially randomized phase II trial studies how well brentuximab vedotin or crizotinib and combination chemotherapy works in treating patients with newly diagnosed stage II-IV anaplastic large cell lymphoma. Monoclonal antibody-drug conjugates, such as brentuximab vedotin, can block cancer growth in different ways by targeting certain cells. Crizotinib and methotrexate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy 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. It is not yet known whether brentuximab vedotin and combination chemotherapy is more effective than crizotinib and combination chemotherapy in treating anaplastic large cell lymphoma.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the tolerability of brentuximab vedotin given in combination with standard chemotherapy (anaplastic large cell lymphoma [ALCL]99) and to determine the tolerability of crizotinib given in combination with chemotherapy (ALCL99).

II. To estimate the event free survival (EFS) of Arm brentuximab vedotin (BV) and Arm crizotinib (CZ) and contrast these to historical control data.

SECONDARY OBJECTIVES:

I. To determine the prognostic significance of minimal disseminated disease (MDD) at diagnosis and minimal residual disease (MRD) as measured by real-time (RT)-polymerase chain reaction (PCR) in peripheral blood.

OUTLINE: Patients are assigned or randomized into 1 of 2 treatment arms.

ARM BV:

COURSE A (COURSES 1, 3, AND 5): Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1, dexamethasone orally (PO) twice daily (BID) or IV on days 1-5, ifosfamide IV over 60 minutes on days 1-5, methotrexate IV over 3 hours on day 1, cytarabine IV over 1-30 minutes every 12 hours for 4 doses on days 4 and 5, and etoposide IV over 2 hours on days 4 and 5.

COURSE B (COURSES 2, 4, AND 6): Patients receive brentuximab vedotin, dexamethasone, and methotrexate as in Arm BV, Course A. Patients also receive cyclophosphamide IV over 15-30 minutes on days 1-5 and doxorubicin hydrochloride IV over 1-15 minutes on days 4 and 5.

ARM CZ:

COURSE A (COURSES 1, 3, AND 5): Patients receive crizotinib PO BID on
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • EFS [ Time Frame: Time from study entry until progressive disease, relapse, or death, assessed up to 60 months ]
    The EFS for each of the treatment regimens will be compared to the fixed standard using Woolson's 1-sample log-rank test.
  • Occurrence of grade 3+ non-hematologic adverse events, using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 60 months ]
    Toxicities will be summarized by individual toxicity counts and incidence rate separated by arm and course.


Original Primary Outcome:

  • Occurrence of grade 3+ non-hematologic adverse events, using the National Cancer Institute (NCI) CTCAE version (v)4.0 [ Time Frame: Up to 60 months ]
    These adverse event rates will be compared to the null hypothesis rate of 5% using an exact test for proportions. Toxicities will be summarized by individual toxicity counts and incidence rate separated by arm and course.
  • EFS [ Time Frame: Time from study entry until progressive disease, relapse, or death, assessed up to 60 months ]
    The EFS for each of the treatment regimens will be compared to the fixed standard using Woolson's 1-sample log-rank test.


Current Secondary Outcome: Changes on levels of MRD [ Time Frame: Baseline up to day 21 (course 1) ]

Analyzed using the log-rank test.


Original Secondary Outcome: Same as current

Information By: National Cancer Institute (NCI)

Dates:
Date Received: November 4, 2013
Date Started: November 2013
Date Completion:
Last Updated: May 23, 2017
Last Verified: May 2017