Study of Rituximab and Brentuximab Vedotin for Relapsed Classical Hodgkin Lymphoma

Study Overview
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Brief Summary
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This research is being done to study a combination of Brentuximab vedotin and Rituximab for the treatment of relapsed Hodgkin's Lymphoma (HL).

Detailed Description
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This research is being done to study a combination of drugs for relapsed Hodgkin's Lymphoma (HL) that may be easier to tolerate than standard therapies and that does not involve an autologous blood or marrow transplant (BMT, also called a stem cell transplant).The study is for people with HL who have never received treatment for relapsed lymphoma, except for radiation therapy. Usually, when HL relapses for the first time, the standard is to receive combinations of chemotherapy, including an autologous blood or marrow transplant (BMT, also called a stem cell transplant) which has about a 40% cure rate. BMT may cure the HL, but also may be associated with serious side effects and risks. This research looks at a combination of drugs for relapsed HL that may not have the side effects of standard therapies and that does not involve BMT. The goal is to treat the lymphoma effectively with drugs that we expect will have fewer side effects, while avoiding a treatment like BMT.

Official Title
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Pilot Study of Rituximab and Brentuximab Vedotin With Deferred BMT for Relapsed Classical Hodgkin Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: Brentuximab vedotin
* Biological: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 16 years Biopsy-proven diagnosis of classical Hodgkin Lymphoma (regardless of HRS cell CD20 expression) per the World Health Organization classification criteria24; lymphocyte predominant histology is excluded Untreated relapse of classical Hodgkin Lymphoma (with the exception of steroids) as follows:HL that relapsed > 3 months after completion of first-line chemotherapy or combined modality therapy, and has not yet been treated with salvage chemotherapy, Stage I-II HL that relapsed > 3 months after first-line chemotherapy, then relapsed after radiation therapy delivered with curative intent, and has not yet been treated with salvage chemotherapy Radiographically measurable disease (> 1 focus of lymphoma measuring > 1.5 cm) Baseline laboratories: ANC > 1000/uL and platelets > 75,000/uL, unless due to bone marrow involvement by lymphoma, Serum creatinine < 2.0 mg/dL, Total bilirubin < 2.0 mg/dL (excluding Gilbert's syndrome), unless due to lymphoma ECOG performance status 0, 1 or 2. Exclusion Criteria: Active concurrent malignancy with the exception of superficial non-melanoma skin cancer and cervical carcinoma in situ. Primary induction failure, defined as failure to achieve CR with first-line chemotherapy or chemoradiation, disease progression during first-line chemotherapy or chemoradiation, or progression or biopsy-proven disease persistence within 8 weeks of first-line therapy completion Prior brentuximab vedotin or rituximab for lymphoma Grade > 2 peripheral neuropathy HIV infection, active hepatitis B infection, or active hepatitis C infection

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brentuximab vedotin & Rituximab<br>Brentuximab vedotin: Will be administered at 1.8 mg/kg IV over 30 minutes is given for up to 10 doses (cycles), with a cycle length of 21 days. Brentuximab vedotin is first given on day 1 of cycles 1, 2, 3, and 4 as a single agent (weeks 0, 3, 6, and 9, respectively). Four cycles are chosen because of the 12-week median time to CR in the pivotal phase 2 trial of brentuximab vedotin after autologous BMT for HL. Brentuximab vedotin will be administered with Rituximab at 375 mg/m2 IV is given for up to 8 induction doses: day 1 of week 6, 7, 8, and 9; day 1 of week 12, 15, 18 and 21. This is followed by rituximab maintenance (375 mg/m2 IV once every 3 months x 2 doses) to complete a   1 year total course of therapy. | Biological: Brentuximab vedotin<br>* Day 1 every three weeks (weeks 0, 3, 6, 9, ... 27): 1.8 mg/kg IV. Ten doses maximum.<br>* Other names: Adcetris;Biological: Rituximab<br>* Day 1 of weeks 12, 13, 14, 15, 18, 21, 24, and 27: 375 mg/m^2 IV. Additional doses are given at three and six months post week 27.<br>* Other names: Rituxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Failure-free survival | Percentage of participants alive without any of the following: death, disease progression or relapse, or failure to achieve complete remission as defined by the Cheson criteria. Per Cheson Criteria: Complete Response (CR) is disappearance of all evidence of disease; Partial Response (PR) is regression of measurable disease and no new sites (≥50% decrease in sum of product diameters of up to 6 largest dominant masses and splenic/liver nodules), and no increase in size of other nodes/liver/spleen; reduction in target lesions, no growth of non-target or new lesions; Progression is any new lesion or increase by ≥50% of previously involved sites from the nadir | Up to 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of combination of brentuximab vedotin and rituximab in relapsed classical Hodgkin's Lymphoma | Percentage of participants with grade 3-4 adverse events by CTCAE 4.0. | Up to 7 months | 
| Survival | Percentage of participants alive with and without disease relapse. | Up to 7 months | 
| Response rate | Percentage of participants with partial and complete remissions as defined by Cheson criteria: Complete Response (CR) is disappearance of all evidence of disease; Partial Response (PR) is regression of measurable disease and no new sites (≥50% decrease in sum of product diameters of up to 6 largest dominant masses and splenic/liver nodules), and no increase in size of other nodes/liver/spleen; reduction in target lesions, no growth of non-target or new lesions | Up to 7 months | 
| Time to best response | Median number of weeks from protocol initiation to best response. | Up to 7 months | 
| Duration of response | Median number of weeks that best response was maintained until disease relapse or death. | Up to 7 months | 
| Measurement of circulating clonotypic B cells (CCBCs) | Median percentage change in CCBCs between initiation and completion of study. | Pre-study, Day 1, Week 12, Week 18, Week 24, Week 30, and time of relapse | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cHL, Hodgkin lymphoma, Lymphoma, relapsed Lymphoma, SGN-35, Brentuximab Vedotin, Rituxan, Rituximab