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.
PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) and/or recommended Phase 2 dose of brentuximab vedotin in combination with gemcitabine 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 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 15 more 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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
46
Given IV
Given IV
Children's Hospital of Alabama
Birmingham, Alabama, United States
Phoenix Childrens Hospital
Phoenix, Arizona, United States
Kaiser Permanente Downey Medical Center
Downey, California, United States
Loma Linda University Medical Center
Loma Linda, California, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Maximum Tolerated Dose (MTD) for Brentuximab Vedotin
MTD was determined as the maximum dose at which fewer than one-third of patients experience Dose Limiting Toxicities (DLT) as assessed by National Cancer Institute (NCI) CTCAE v 4.0 during Cycle 1 of therapy. Gemcitabine was administered on days 1 and 8 of a 21 day cycle at a fixed dose. Brentuximab vedotin was investigated at a starting dose of 1.4 mg/kg administered on day 1 and escalated if tolerated.
Time frame: During cycle 1 of protocol therapy (21 days)
Adverse Events Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
The number of eligible patients assigned to receive brentuximab vedotin in combination with gemcitabine that experienced CTC Version 4, grade 3 or higher adverse events during Phase 1 and Phase 2.
Time frame: 13 months from first dose
The Number of Patients With Relapsed or Refractory HL Who Achieved Complete Response (CR)
The number of patients who experienced complete Response (CR) within the first four cycles. By modern response criteria, those with partial response (PR) or stable disease with all target lesions with Deauville scores \<=3 after cycle 4 are also considered as CR. Patients were assessed after treatment with four cycles of gemcitabine with brentuximab vedotin. CR was only reported for Dose level 2 across both phases of study.
Time frame: After 4 cycles (21 days per cycle) of protocol therapy
The Number of Patients Who Had Disease Response Assessed by Deauville Scales Among Those in Phase I With Dose Level 2.
The Deauville five-point scale was used to assess the number of participants with complete response (CR) and partial response (PR). A lower score indicates a better outcome. Scores of 1-3 represent CR and 4-5 represent PR.
Time frame: Up to 13 months from first dose
Percentage of Patients Who Achieved Overall Response (OR) as Measured by Complete Response (CR) and Partial Response (PR)
The percentage of patients who experienced complete Response (CR) within the first four cycles.By modern response criteria, those with partial response (PR) or stable disease with all target lesions with Deauville scores \<=3 after cycle 4 are also considered as CR. Patients were assessed after treatment with four cycles of gemcitabine with brentuximab vedotin. CR was only reported for Dose level 2 across both phases of study.
Time frame: After 4 cycles (21 days per cycle) of protocol therapy
The Number of Patients Who Had Successful Peripheral Blood Stem Cell (PBSC) Collection
Successful PBSC collection was defined as a collection of more than 2x10\^6 CD34 positive cells.
Time frame: From 1 to 5 cycles
Plasma Level of Thymus and Activation-Regulated Chemokine (TARC)
Limit to 41 evaluable patients who received dose 1.8 mg/kg
Time frame: From baseline to time prior to cycle 2
Correlation Between Micro Ribonucleic Acid (miRNA) and Disease Response to Protocol Treatment
Limit to 41 evaluable patients who received dose 1.8 mg/kg
Time frame: From the end of first dose to the end of last dose (Up to 13 Months)
Number of Patients With FcyRIIIa-158 V/F (Valine/Phenylalanine) Polymorphism
Among patients who received 1.8mg/kg dose, the frequency of the FcγRIIIa-158 V/F polymorphism are described.
Time frame: From the end of first dose to the end of last dose (Up to 13 Months)
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Valley Children's Hospital
Madera, California, United States
UCSF Benioff Children's Hospital Oakland
Oakland, California, United States
Children's Hospital of Orange County
Orange, California, United States
Lucile Packard Children's Hospital Stanford University
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Sacramento, California, United States
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