Study of Rituximab and Brentuximab Vedotin for Relapsed Classical Hodgkin Lymphoma

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Terminated

CT.gov ID

NCT01900496

Collaborator

Genentech, Inc. (Industry)

Enrollment

Location

Arm

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: Brentuximab vedotin Biological: Rituximab	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 1, 2014

Actual Primary Completion Date :

Jul 1, 2017

Actual Study Completion Date :

Jul 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Brentuximab vedotin & Rituximab 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 Day 1 every three weeks (weeks 0, 3, 6, 9, ... 27): 1.8 mg/kg IV. Ten doses maximum. Other Names: SGN-35 Adcetris Biological: Rituximab 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. Other Names: Rituxan

Arm

Intervention/Treatment

Experimental: Brentuximab vedotin & Rituximab

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

Day 1 every three weeks (weeks 0, 3, 6, 9, ... 27): 1.8 mg/kg IV. Ten doses maximum.

Other Names:

SGN-35

Adcetris

Biological: Rituximab

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.

Other Names:

Rituxan

Outcome Measures

Primary Outcome Measures

Failure-free survival [Up to 7 months]
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 [Up to 7 months]
Percentage of participants with grade 3-4 adverse events by CTCAE 4.0.
Survival [Up to 7 months]
Percentage of participants alive with and without disease relapse.
Response rate [Up to 7 months]
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 [Up to 7 months]
Median number of weeks from protocol initiation to best response.
Duration of response [Up to 7 months]
Median number of weeks that best response was maintained until disease relapse or death.
Measurement of circulating clonotypic B cells (CCBCs) [Pre-study, Day 1, Week 12, Week 18, Week 24, Week 30, and time of relapse]
Median percentage change in CCBCs between initiation and completion of study.

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 100 Years

Sexes Eligible for Study:

All

Accepts 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