Combination Chemotherapy With or Without Rituximab in Treating Participants With Stage III-IV Classic Hodgkin Lymphoma

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00654732
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 58
• Locations: 4
• Arms: 2
• Actual Duration (Months): 125.6
• Patients Per Site: 14.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This phase II trial studies how well combination chemotherapy with or without rituximab works in treating participants with stage III-IV classic Hodgkin lymphoma. Monoclonal antibodies, such as rituximab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving rituximab with combination chemotherapy may work better in treating participants with classic Hodgkin lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Classic Hodgkin Lymphoma; Lugano Classification Stage III Hodgkin Lymphoma AJCC v8; Lugano Classification Stage IV Hodgkin Lymphoma AJCC v8	Drug: Bleomycin; Drug: Dacarbazine; Drug: Doxorubicin Hydrochloride; Biological: Rituximab; Drug: Vinblastine	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To evaluate the event free survival (EFS) following therapy with rituximab plus adriamycin (doxorubicin hydrochloride), bleomycin, vinblastine, and dacarbazine (ABVD) or standard ABVD in patients with newly diagnosed classical Hodgkin lymphoma who have poor prognosis defined as International prognostic score (IPS) of > 2.

SECONDARY OBJECTIVES:

1. To compare the effect of the two treatment arms on positron emission tomography (PET) scan results after 2 cycles of therapy.

2. To compare the effect of the two treatment arms on the level of circulating malignant Hodgkin stem cells.

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM A: Participants receive rituximab intravenously (IV) over 7 hours on days 1, 8, 15, and 22 of course 1 and on days 1 and 8 of course 2. Participants also receive doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine IV over 1 hour on days 1 and 15. Treatment with ABVD repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

ARM B: Participants receive doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine as in Arm A.

After completion of study treatment, participants are followed up every 3 months for the first year, every 4 months for the second year, every 6 months for years 3-5, and then annually thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II Study of Rituximab With ABVD Versus Standard ABVD for Patients With Advanced-Stage Classical Hodgkin Lymphoma With Poor Risk Features (IPS Score > 2)
• Actual Study Start Date: Mar 19, 2008
• Actual Primary Completion Date: Sep 5, 2018
• Actual Study Completion Date: Sep 5, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A (rituximab, combination chemotherapy) Participants receive rituximab intravenously IV over 7 hours on days 1, 8, 15, and 22 of course 1 and on days 1 and 8 of course 2. Participants also receive doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine IV over 1 hour on days 1 and 15. Treatment with ABVD repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.	Drug: Bleomycin; Given IV; Other Names: BLEO BLM ; Drug: Dacarbazine; Given IV; Other Names: 4-(Dimethyltriazeno)imidazole-5-carboxamide 5-(Dimethyltriazeno)imidazole-4-carboxamide Asercit Biocarbazine Dacarbazina Dacarbazina Almirall Dacarbazine - DTIC Dacatic Dakarbazin Deticene Detimedac DIC Dimethyl (triazeno) imidazolecarboxamide Dimethyl Triazeno Imidazol Carboxamide Dimethyl Triazeno Imidazole Carboxamide dimethyl-triazeno-imidazole carboxamide Dimethyl-triazeno-imidazole-carboximide DTIC DTIC-Dome Fauldetic Imidazole Carboxamide Imidazole Carboxamide Dimethyltriazeno WR-139007 ; Drug: Doxorubicin Hydrochloride; Given IV; Other Names: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI) ADM Adriacin Adriamycin Adriamycin Hydrochloride Adriamycin PFS Adriamycin RDF ADRIAMYCIN, HYDROCHLORIDE Adriamycine Adriblastina Adriblastine Adrimedac Chloridrato de Doxorrubicina DOX DOXO-CELL Doxolem Doxorubicin.HCl Doxorubin Farmiblastina FI 106 FI-106 hydroxydaunorubicin Rubex ; Biological: Rituximab; Given IV; Other Names: ABP 798 BI 695500 C2B8 Monoclonal Antibody Chimeric Anti-CD20 Antibody CT-P10 IDEC-102 IDEC-C2B8 IDEC-C2B8 Monoclonal Antibody MabThera Monoclonal Antibody IDEC-C2B8 PF-05280586 Rituxan Rituximab Biosimilar ABP 798 Rituximab Biosimilar BI 695500 Rituximab Biosimilar CT-P10 Rituximab Biosimilar GB241 Rituximab Biosimilar IBI301 Rituximab Biosimilar PF-05280586 Rituximab Biosimilar RTXM83 Rituximab Biosimilar SAIT101 RTXM83 ; Drug: Vinblastine; Given IV; Other Names: Vincaleucoblastine VLB
Active Comparator: Arm B (combination chemotherapy) Participants receive doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine as in Arm A.	Drug: Bleomycin; Given IV; Other Names: BLEO BLM ; Drug: Dacarbazine; Given IV; Other Names: 4-(Dimethyltriazeno)imidazole-5-carboxamide 5-(Dimethyltriazeno)imidazole-4-carboxamide Asercit Biocarbazine Dacarbazina Dacarbazina Almirall Dacarbazine - DTIC Dacatic Dakarbazin Deticene Detimedac DIC Dimethyl (triazeno) imidazolecarboxamide Dimethyl Triazeno Imidazol Carboxamide Dimethyl Triazeno Imidazole Carboxamide dimethyl-triazeno-imidazole carboxamide Dimethyl-triazeno-imidazole-carboximide DTIC DTIC-Dome Fauldetic Imidazole Carboxamide Imidazole Carboxamide Dimethyltriazeno WR-139007 ; Drug: Doxorubicin Hydrochloride; Given IV; Other Names: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI) ADM Adriacin Adriamycin Adriamycin Hydrochloride Adriamycin PFS Adriamycin RDF ADRIAMYCIN, HYDROCHLORIDE Adriamycine Adriblastina Adriblastine Adrimedac Chloridrato de Doxorrubicina DOX DOXO-CELL Doxolem Doxorubicin.HCl Doxorubin Farmiblastina FI 106 FI-106 hydroxydaunorubicin Rubex ; Drug: Vinblastine; Given IV; Other Names: Vincaleucoblastine VLB

Outcome Measures

Primary Outcome Measures

1. Event-free Survival (EFS) Rate [From the start of study treatment up to 3 years]

   EFS will be estimated using the Kaplan-Meier method. The log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model will be utilized to include multiple covariates in the time-to-event analysis. Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 17 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Previously untreated patient with classical Hodgkin's lymphoma patients with stage III and IV

• International Prognostic Score of > 2 (patient must have > 2 of the following risk features: Male, >= 45 years of age, stage IV, albumin < 4, white blood cell count [WBC] >= 15, lymphocytes < 8% or < 600, hemoglobin [Hgb] < 10.5)

• Must sign a consent form

• Absolute neutrophil count (ANC) >= 1,500/microL

• Platelet > 100,000/microL

• Left ventricular ejection fraction (LVEF) >= 50% by multigated acquisition (MUGA) scan or echocardiogram

• Serum creatinine < 2 mg/dl

• Serum bilirubin < 2 mg/dl

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2 x upper limit of normal (ULN)

• Bi-dimensionally measurable disease

Exclusion Criteria:

• Lymphocyte predominant Hodgkin's lymphoma

• Known human immunodeficiency virus (HIV) infection

• Pregnant women and women of child bearing age who are not practicing adequate contraception

• Prior chemotherapy or radiation therapy

• Severe pulmonary disease as judged by the principal investigator (PI) including chronic obstructive pulmonary disease (COPD) and asthma

• Active infection requiring treatment with intravenous therapy

• Presence of central nervous system (CNS) lymphoma

• Concomitant malignancies or previous malignancies within the last 5 years (exception made for adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of cervix)

• Active hepatitis B or C infection

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida	United States	33136
2	Rush University Medical Center	Chicago	Illinois	United States	60612
3	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
4	M D Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Hun Lee, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 17, 2012

More Information

Additional Information:

• MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00654732
• Other Study ID Numbers: 2007-0144; NCI-2018-01855; 2007-0144; P30CA016672
• First Posted: Apr 9, 2008
• Last Update Posted: Feb 28, 2020
• Last Verified: Feb 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lymphoma; Hodgkin Disease; Rituximab; Antineoplastic Agents, Immunological; Doxorubicin; Liposomal doxorubicin; Dacarbazine; Bleomycin; Vinblastine; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Imidazole

Study Results

Participant Flow

Recruitment Details	Frontline advance stage hodgkin lymphoma

Arm/Group Title	RABVD	ABVD
Arm/Group Description	Rituximab Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine	Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine
Period Title: Overall Study
STARTED	26	32
COMPLETED	22	26
NOT COMPLETED	4	6

Baseline Characteristics

Arm/Group Title	RABVD	ABVD	Total
Arm/Group Description	Rituximab Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine	Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine	Total of all reporting groups
Overall Participants	26	32	58
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	15 57.7%	16 50%	31 53.4%
>=65 years	11 42.3%	16 50%	27 46.6%
Sex: Female, Male (Count of Participants)
Female	12 46.2%	10 31.3%	22 37.9%
Male	14 53.8%	22 68.8%	36 62.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	NA NaN	NA NaN	NA NaN
Asian	NA NaN	NA NaN	NA NaN
Native Hawaiian or Other Pacific Islander	NA NaN	NA NaN	NA NaN
Black or African American	NA NaN	NA NaN	NA NaN
White	NA NaN	NA NaN	NA NaN
More than one race	NA NaN	NA NaN	NA NaN
Unknown or Not Reported	26 100%	32 100%	58 100%
Region of Enrollment (participants) [Number]
United States	NA NaN	NA NaN	NA NaN

Outcome Measures

1. Primary Outcome

Title	Event-free Survival (EFS) Rate
Description	EFS will be estimated using the Kaplan-Meier method. The log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model will be utilized to include multiple covariates in the time-to-event analysis. Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate.
Time Frame	From the start of study treatment up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RABVD	ABVD
Arm/Group Description	Experimental Arm Rituximab, Adriamycin, Bleomycin, Vinblastine, and Dacarbazine	Control Arm (Adriamycin, Bleomycin, Vinblastine, and Dacarbazine)
Measure Participants	22	26
Count of Participants [Participants]	17 65.4%	20 62.5%

Adverse Events

Time Frame	4 years and 6 months
Arm/Group Title	RABVD		ABVD
Arm/Group Description	Rituximab chemotherapy		Chemotherapy only
All Cause Mortality
	RABVD		ABVD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/26 (19.2%)		6/32 (18.8%)
Serious Adverse Events
	RABVD		ABVD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/26 (50%)		13/32 (40.6%)
Blood and lymphatic system disorders
Neutropennia	13/26 (50%)		13/32 (40.6%)
Anemia	1/26 (3.8%)		2/32 (6.3%)
Thrombocytopenia	1/26 (3.8%)		2/32 (6.3%)
Immune system disorders
Infection	4/26 (15.4%)		1/32 (3.1%)
Nervous system disorders
Neuropathy	1/26 (3.8%)		3/32 (9.4%)
Respiratory, thoracic and mediastinal disorders
Respiratory Complicaton	0/26 (0%)		2/32 (6.3%)
Other (Not Including Serious) Adverse Events
	RABVD		ABVD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/32 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.