Phase 2 Study of Rituximab-ABVD in Classical Hodgkin Lymphoma

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Completed
• CT.gov ID: NCT00369681
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 51
• Locations: 4
• Arm: 1
• Duration (Months): 101
• Patients Per Site: 12.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating patients with newly diagnosed stage II, stage III, or stage IV Hodgkin's lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: Bleomycin; Biological: Rituximab; Drug: Dacarbazine; Drug: Doxorubicin; Drug: Vinblastine	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Investigate plasma DNA biomarkers, including plasma clonal immunoglobulin DNA, tumor suppressor gene methylation, and Epstein-Barr virus DNA, in patients receiving rituximab and doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine (ABVD) for newly diagnosed stage II-IV classical Hodgkin's lymphoma.

• Characterize the impact of rituximab on these markers.

• Characterize the relationship between marker detection and clinical outcome.

Secondary

• Estimate the event-free survival of patients with newly diagnosed Hodgkin's lymphoma treated with rituximab and ABVD.

• Assess the presence of Hodgkin's lymphoma stem cells in peripheral blood mononuclear cells at baseline, after treatment with rituximab, and after treatment with ABVD.

• Assess whether plasma DNA biomarkers add information to fludeoxyglucose F 18 positron emission tomography (FDG-PET) in assessing tumor response.

OUTLINE: Patients receive doxorubicin hydrochloride IV, vinblastine IV, bleomycin IV, and dacarbazine IV (ABVD) on days 1 and 15 of all courses. Patients also receive rituximab IV on days -6, 1, 8, 15, and 22 of ABVD course 1 and on day 1 only of ABVD courses 2, 4, and 6. Treatment repeats every 28 days for 6-8 courses in the absence of disease progression or unacceptable toxicity.

Patients with bulky disease may undergo radiotherapy.

Plasma samples are obtained during treatment for investigation of tumor markers (e.g., immunoglobulin rearrangement, patterns of DNA methylation, and the presence of Epstein-Barr virus DNA). Patients undergo fludeoxyglucose F18 positron emission tomography periodically during the study.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 51 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Rituximab and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Hodgkin's Lymphoma
• Study Start Date: May 1, 2006
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: R-ABVD ABVD (doxorubicin; vinblastine; bleomycin; dacarbazine) given as standard for 6-8 cycles. Rituximab given 375 mg/m^2 Cycle 1 Days -6, 1, 8, 15, and 22. Rituximab given 375 mg/m^2 Cycles 2, 4, and 6 Day 1.	Drug: Bleomycin; Other Names: Blenoxane ; Biological: Rituximab; Other Names: Rituxan ; Drug: Dacarbazine; Other Names: DTIC DTIC-Dome ; Drug: Doxorubicin; Other Names: Adriamycin ; Drug: Vinblastine; Other Names: Velban Alkaban

Outcome Measures

Primary Outcome Measures

1. Effect of Rituximab on EBV(+) Tumors [Up to 56 months]

   Number of relapses among participants who had tumors positive for Epstein-Barr virus (EBV).

2. Relationship Between Marker Detection and Clinical Outcome [3 years]

   Number of relapses for participants who did and did not have re-emergence of clonal CD27(+) ALDH(+) B cells after completing study intervention.

Secondary Outcome Measures

1. Event-free Survival [3 years]

   Percentage of participants who did not experience death, relapse, or progression (worsening) of their lymphoma.

2. Addition of Information to Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) by Plasma DNA Biomarkers [5 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed classical Hodgkin's lymphoma

• No lymphocyte-predominant histology

• Stage II, III, or IV disease

• Newly diagnosed disease

PATIENT CHARACTERISTICS:

• Performance status 0-2

• Creatinine < 2.0 mg/dL

• Bilirubin < 5 mg/dL

• Not pregnant or nursing

• No HIV positivity

• Hepatitis B surface antigen negative

• No active concurrent malignancy except for superficial nonmelanoma skin cancer or cervical carcinoma in situ

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy or radiotherapy for Hodgkin's lymphoma

• Steroids allowed if medically required before chemotherapy initiation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-3000
2	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa	United States	52242-1009
3	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
4	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• National Cancer Institute (NCI)

Investigators

• Study Chair: Yvette L. Kasamon, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Documents (Full-Text)

None provided.

More Information

Publications

• Kasamon YL, Jacene HA, Gocke CD, Swinnen LJ, Gladstone DE, Perkins B, Link BK, Popplewell LL, Habermann TM, Herman JM, Matsui WH, Jones RJ, Ambinder RF. Phase 2 study of rituximab-ABVD in classical Hodgkin lymphoma. Blood. 2012 May 3;119(18):4129-32. doi: 10.1182/blood-2012-01-402792. Epub 2012 Feb 16.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT00369681
• Other Study ID Numbers: J0615; P30CA006973; NA_00002473
• First Posted: Aug 29, 2006
• Last Update Posted: Aug 27, 2018
• Last Verified: Jul 1, 2018

• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: stage II adult Hodgkin lymphoma; stage III adult Hodgkin lymphoma; stage IV adult Hodgkin lymphoma; adult lymphocyte depletion Hodgkin lymphoma; adult mixed cellularity Hodgkin lymphoma; adult nodular sclerosis Hodgkin lymphoma
• Additional relevant MeSH terms: Lymphoma; Hodgkin Disease; Rituximab; Doxorubicin; Dacarbazine; Bleomycin; Vinblastine

Study Results

Participant Flow

Pre-assignment Detail	One subject withdrew consent prior to initiating the study.

Arm/Group Title	R-ABVD
Arm/Group Description	ABVD (Adriamycin/doxorubicin; vinblastine; bleomycin; dacarbazine) given as standard for 6-8 cycles. Rituximab given 375 mg/m^2 Cycle 1 Days -6, 1, 8, 15, and 22. Rituximab given 375 mg/m^2 Cycles 2, 4, and 6 Day 1.
Period Title: Overall Study
STARTED	50
COMPLETED	49
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	R-ABVD
Arm/Group Description	ABVD (Adriamycin/doxorubicin; vinblastine; bleomycin; dacarbazine) given as standard for 6-8 cycles. Rituximab given 375 mg/m^2 Cycle 1 Days -6, 1, 8, 15, and 22. Rituximab given 375 mg/m^2 Cycles 2, 4, and 6 Day 1.
Overall Participants	49
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	33
Sex: Female, Male (Count of Participants)
Female	23 46.9%
Male	26 53.1%
Region of Enrollment (participants) [Number]
United States	49 100%

Outcome Measures

1. Primary Outcome

Title	Effect of Rituximab on EBV(+) Tumors
Description	Number of relapses among participants who had tumors positive for Epstein-Barr virus (EBV).
Time Frame	Up to 56 months

Outcome Measure Data

Analysis Population Description

Only 4 participants had EBV(+) tumors.

Arm/Group Title	R-ABVD
Arm/Group Description	ABVD (Adriamycin/doxorubicin; vinblastine; bleomycin; dacarbazine) given as standard for 6-8 cycles. Rituximab given 375 mg/m^2 Cycle 1 Days -6, 1, 8, 15, and 22. Rituximab given 375 mg/m^2 Cycles 2, 4, and 6 Day 1.
Measure Participants	4
Number [relapses]	0

2. Primary Outcome

Title	Relationship Between Marker Detection and Clinical Outcome
Description	Number of relapses for participants who did and did not have re-emergence of clonal CD27(+) ALDH(+) B cells after completing study intervention.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Only 21 participants had a detectable CD27(+) ALDH(+) clone prior to study intervention. The remaining participants either did not have such a clone or did not have a sample tested to look for a clone.

Arm/Group Title	R-ABVD
Arm/Group Description	ABVD (Adriamycin/doxorubicin; vinblastine; bleomycin; dacarbazine) given as standard for 6-8 cycles. Rituximab given 375 mg/m^2 Cycle 1 Days -6, 1, 8, 15, and 22. Rituximab given 375 mg/m^2 Cycles 2, 4, and 6 Day 1.
Measure Participants	21
No re-emergence of clone	0
Re-emergence of clone	2

3. Secondary Outcome

Title	Event-free Survival
Description	Percentage of participants who did not experience death, relapse, or progression (worsening) of their lymphoma.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

All evaluable participants.

Arm/Group Title	R-ABVD
Arm/Group Description	ABVD (Adriamycin/doxorubicin; vinblastine; bleomycin; dacarbazine) given as standard for 6-8 cycles. Rituximab given 375 mg/m^2 Cycle 1 Days -6, 1, 8, 15, and 22. Rituximab given 375 mg/m^2 Cycles 2, 4, and 6 Day 1.
Measure Participants	49
Number (95% Confidence Interval) [percentage of participants]	83 169.4%

4. Secondary Outcome

Title	Addition of Information to Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) by Plasma DNA Biomarkers
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

Data pertaining to this outcome was not collected.

Arm/Group Title	R-ABVD
Arm/Group Description	ABVD (Adriamycin/doxorubicin; vinblastine; bleomycin; dacarbazine) given as standard for 6-8 cycles. Rituximab given 375 mg/m^2 Cycle 1 Days -6, 1, 8, 15, and 22. Rituximab given 375 mg/m^2 Cycles 2, 4, and 6 Day 1.
Measure Participants	0

Adverse Events

Time Frame	Adverse events were tracked monthly for up to six months.
Adverse Event Reporting Description	Only the following adverse events were collected for this study: all grade 3-5 toxicities; any previously-undescribed toxicity potentially attributable to the addition of the rituximab to the ABVD regimen, regardless of grade; any toxicity associated with infusion of rituximab, regardless of grade.
Arm/Group Title	R-ABVD
Arm/Group Description	ABVD (Adriamycin/doxorubicin; vinblastine; bleomycin; dacarbazine) given as standard for 6-8 cycles. Rituximab given 375 mg/m^2 Cycle 1 Days -6, 1, 8, 15, and 22. Rituximab given 375 mg/m^2 Cycles 2, 4, and 6 Day 1.
All Cause Mortality
	R-ABVD
	Affected / at Risk (%)	# Events
Total	1/50 (2%)
Serious Adverse Events
	R-ABVD
	Affected / at Risk (%)	# Events
Total	16/50 (32%)
Blood and lymphatic system disorders
Febrile neutropenia	7/50 (14%)	7
Infections and infestations
Non-neutropenic infection	9/50 (18%)	9
Investigations
Other, not specified	4/50 (8%)	4
Respiratory, thoracic and mediastinal disorders
Pulmonary toxicity	3/50 (6%)	3
Vascular disorders
Thrombosis	4/50 (8%)	4
Other (Not Including Serious) Adverse Events
	R-ABVD
	Affected / at Risk (%)	# Events
Total	0/50 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.