Clinical Trial: Brentuximab Vedotin and Gemcitabine Hydrochloride in Treating Younger Patients With Relapsed or Refractory Hodgkin Lymphoma

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase 1/2 Study of Brentuximab Vedotin (SGN35) in Combination With Gemcitabine for Pediatric and Young Adult Patients With Relapsed or Refractory Hodgkin Lymphoma

Brief Summary: This phase I/II trial studies the side effects and the best dose of brentuximab vedotin when given together with gemcitabine hydrochloride and to see how well they work in treating younger patients with Hodgkin lymphoma that has returned or does not respond to treatment. Monoclonal antibodies, such as brentuximab vedotin, may find cancer cells and help kill them. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving brentuximab vedotin together with gemcitabine hydrochloride may kill more cancer cells.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) and/or recommended Phase 2 dose of brentuximab vedotin in combination with gemcitabine (gemcitabine hydrochloride) administered every three weeks to children with relapsed or primary refractory Hodgkin lymphoma (HL).

II. To define and describe the toxicities of brentuximab vedotin in combination with gemcitabine administered on this schedule.

III. To determine the complete response (CR) rate after treatment with four cycles of gemcitabine with brentuximab vedotin among patients with relapsed or refractory HL.

SECONDARY OBJECTIVES:

I. To preliminarily define the antitumor activity of brentuximab vedotin in combination with gemcitabine within the confines of a Phase 1 study.

II. To describe the overall response rate (ORR) after 4 cycles of therapy among patients with relapsed or refractory HL.

III. To describe the proportion of patients with HL able to mobilize an adequate yield of cluster of differentiation (CD) 34+ stem cells after gemcitabine with brentuximab vedotin.

IV. To describe the relationship between disease response among patients with HL and changes in thymus and activation-regulated chemokine (TARC) during treatment, and to determine if specific micro ribonucleic acid (miRNA) profiles correlate with response to treatment.

V. To describe the frequency of the Fc gamma receptor IIIa (FcγRIIIa)-158 valine (V)/phenylalanine (F) polymorphism among patients who experience pulmonary toxicity on this prot
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • CR rate (Part B) [ Time Frame: At 12 weeks ]
  • Incidence of adverse events graded according to NCI CTCAE v4.0 (Part A) [ Time Frame: Up to 5 years ]
  • MTD of brentuximab vedotin in combination with gemcitabine hydrochloride defined as the maximum dose at which fewer than one-third of patients experience dose limiting toxicity (DLT) as assessed by National Cancer Institute (NCI) CTCAE v 4.0 (Part A) [ Time Frame: Up to 21 days ]


Original Primary Outcome:

  • MTD of brentuximab vedotin in combination with gemcitabine hydrochloride defined as the maximum dose at which fewer than one-third of patients experience DLT as assessed by NCI CTCAE v 4.0 (Part A) [ Time Frame: Up to 21 days ]
  • Incidence of adverse events graded according to NCI CTCAE v4.0 (Part A) [ Time Frame: Up to 5 years ]
  • CR rate (Part B) [ Time Frame: At 12 weeks ]


Current Secondary Outcome:

  • Disease response (Part A) [ Time Frame: Up to 5 years ]
    Reported descriptively.
  • Frequency of the FcyRIIIa-158 V/F polymorphism [ Time Frame: Up to day 1 of course 16 ]
    Described among patients who experience any pulmonary toxicity.
  • miRNA profile [ Time Frame: Up to day 1 of course 16 ]
    The association between response and miRNA profile will be explored by comparing the specific miRNA level or change over time between patients with CR versus < CR by 2-sample t-test or Wilcoxon rank sum test.
  • ORR (Part B) [ Time Frame: At 12 weeks ]
  • Plasma level of TARC [ Time Frame: Up to day 1 of course 16 ]
    Summarized by standard descriptive statistics such as mean, standard deviation, median, and range. Plasma level of TARC after each cycle or the change in level of TARC from baseline will be compared between patients with CR versus < CR by two-sample t-test or two-sample Wilcoxon rank sum test.
  • Toxicity as assessed by NCI CTCAE version 4.0 (Part B) [ Time Frame: Up to 30 days after completion of study treatment ]


Original Secondary Outcome:

  • Disease response (Part A) [ Time Frame: Up to 5 years ]
    Reported descriptively.
  • ORR (Part B) [ Time Frame: At 12 weeks ]
  • Toxicity as assessed by NCI CTCAE version 4.0 (Part B) [ Time Frame: Up to 30 days after completion of study treatment ]


Information By: National Cancer Institute (NCI)

Dates:
Date Received: January 29, 2013
Date Started: January 2013
Date Completion:
Last Updated: May 11, 2017
Last Verified: May 2017