Brentuximab Vedotin and Gemcitabine Hydrochloride in Treating Younger Patients With Relapsed or Refractory Hodgkin Lymphoma
|ClinicalTrials.gov Identifier: NCT01780662|
Recruitment Status : Active, not recruiting
First Posted : January 31, 2013
Last Update Posted : January 25, 2018
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Adult Hodgkin Lymphoma Recurrent Childhood Hodgkin Lymphoma Refractory Childhood Hodgkin Lymphoma||Drug: Brentuximab Vedotin Drug: Gemcitabine Hydrochloride Other: Laboratory Biomarker Analysis||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||72 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||January 31, 2013|
|Estimated Primary Completion Date :||March 1, 2018|
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)
- 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 ]
- 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 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01780662
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|Principal Investigator:||Peter Cole||Children's Oncology Group|