Brentuximab Vedotin and Gemcitabine Hydrochloride in Treating Younger Patients With Relapsed or Refractory Hodgkin Lymphoma
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.
Recurrent Adult Hodgkin Lymphoma
Recurrent Childhood Hodgkin Lymphoma
Refractory Childhood Hodgkin Lymphoma
Drug: Brentuximab Vedotin
Drug: Gemcitabine Hydrochloride
Other: Laboratory Biomarker Analysis
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- CR rate (Part B) [ Time Frame: At 12 weeks ] [ Designated as safety issue: No ]
- Incidence of adverse events graded according to NCI CTCAE v4.0 (Part A) [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
- 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 ] [ Designated as safety issue: Yes ]
- Disease response (Part A) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Reported descriptively.
- Frequency of the FcyRIIIa-158 V/F polymorphism [ Time Frame: Up to day 1 of course 16 ] [ Designated as safety issue: No ]Described among patients who experience any pulmonary toxicity.
- miRNA profile [ Time Frame: Up to day 1 of course 16 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]
- Plasma level of TARC [ Time Frame: Up to day 1 of course 16 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 2013|
|Estimated Primary Completion Date:||October 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (brentuximab vedotin, gemcitabine hydrochloride)
Patients receive brentuximab vedotin IV over 30 minutes on day 1 and gemcitabine hydrochloride IV over 100 minutes on days 1 and 8. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity. Patients with CR after any course may go off protocol therapy for stem cell transplant.
Drug: Brentuximab Vedotin
Other Names:Drug: Gemcitabine Hydrochloride
Other Names:Other: Laboratory Biomarker Analysis
Optional correlative studies (Part B only)
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.
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 protocol.
OUTLINE: This is a phase I, dose-escalation study of brentuximab vedotin followed by a phase II study. (Phase I completed as of amendment 4)
Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1 and gemcitabine hydrochloride IV over 100 minutes on days 1 and 8. Treatment repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity. Patients with CR after any course may go off protocol therapy for stem cell transplant.
After completion of study treatment, patients are followed up at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01780662
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|Principal Investigator:||Peter Cole||Children's Oncology Group|