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Study of Rituximab and Brentuximab Vedotin for Relapsed Classical Hodgkin Lymphoma

Primary Purpose

Lymphoma

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Brentuximab vedotin
Rituximab
Sponsored by
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring cHL, Hodgkin lymphoma, Lymphoma, relapsed Lymphoma, SGN-35, Brentuximab Vedotin, Rituxan, Rituximab

Eligibility Criteria

16 Years - 100 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The Sidney Kimmel Comprehensive Canceer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Brentuximab vedotin & Rituximab

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
Survival
Percentage of participants alive with and without disease relapse.
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
Time to best response
Median number of weeks from protocol initiation to best response.
Duration of response
Median number of weeks that best response was maintained until disease relapse or death.
Measurement of circulating clonotypic B cells (CCBCs)
Median percentage change in CCBCs between initiation and completion of study.

Full Information

First Posted
July 11, 2013
Last Updated
October 16, 2018
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01900496
Brief Title
Study of Rituximab and Brentuximab Vedotin for Relapsed Classical Hodgkin Lymphoma
Official Title
Pilot Study of Rituximab and Brentuximab Vedotin With Deferred BMT for Relapsed Classical Hodgkin Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Terminated
Why Stopped
Low accrual
Study Start Date
June 2014 (Actual)
Primary Completion Date
July 2017 (Actual)
Study Completion Date
July 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
Genentech, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
cHL, Hodgkin lymphoma, Lymphoma, relapsed Lymphoma, SGN-35, Brentuximab Vedotin, Rituxan, Rituximab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Brentuximab vedotin & Rituximab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Brentuximab vedotin
Other Intervention Name(s)
SGN-35, Adcetris
Intervention Description
Day 1 every three weeks (weeks 0, 3, 6, 9, ... 27): 1.8 mg/kg IV. Ten doses maximum.
Intervention Type
Biological
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
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.
Primary Outcome Measure Information:
Title
Failure-free survival
Description
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
Time Frame
Up to 7 months
Secondary Outcome Measure Information:
Title
Safety of combination of brentuximab vedotin and rituximab in relapsed classical Hodgkin's Lymphoma
Description
Percentage of participants with grade 3-4 adverse events by CTCAE 4.0.
Time Frame
Up to 7 months
Title
Survival
Description
Percentage of participants alive with and without disease relapse.
Time Frame
Up to 7 months
Title
Response rate
Description
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
Time Frame
Up to 7 months
Title
Time to best response
Description
Median number of weeks from protocol initiation to best response.
Time Frame
Up to 7 months
Title
Duration of response
Description
Median number of weeks that best response was maintained until disease relapse or death.
Time Frame
Up to 7 months
Title
Measurement of circulating clonotypic B cells (CCBCs)
Description
Median percentage change in CCBCs between initiation and completion of study.
Time Frame
Pre-study, Day 1, Week 12, Week 18, Week 24, Week 30, and time of relapse

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nina Wagner-Johnston, MD
Organizational Affiliation
The Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Sidney Kimmel Comprehensive Canceer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study of Rituximab and Brentuximab Vedotin for Relapsed Classical Hodgkin Lymphoma

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