Radiation Therapy and Chemotherapy in Treating Patients With Hodgkin's Disease

NCT00002561 | Completed Phase 3 DMC

• 5 other identifiers: HD6CAN-NCIC-HD6E-JHD06NCI-V94-0427CDR0000063481
• Study Type: interventional
• Target: 405
• Locations: 3 countries
• Sites: 22

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high energy x-rays to damage tumor cells. Combining more than one drug or combining chemotherapy with radiation therapy may kill more tumor cells. PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy, with or without chemotherapy, with chemotherapy alone in treating patients with stage I or stage IIA Hodgkin's disease.

Conditions

Hodgkin Lymphoma

Keywords

stage I adult Hodgkin lymphoma; stage II adult Hodgkin lymphoma; adult lymphocyte predominant Hodgkin lymphoma; adult lymphocyte depletion Hodgkin lymphoma; adult nodular sclerosis Hodgkin lymphoma; adult mixed cellularity Hodgkin lymphoma

Outcome Measures

Primary Outcomes (1)

• Survival

  12 year survival comparison

  12 years

Secondary Outcomes (4)

• Freedom from progression

  12 years

• Complete response rate

  12 years

• Second disease progression rate

  5 and 10 years

• Cause-specific survival rate

  5 and 10 years

Study Arms (2)

Radiotherapy or ABVD + Radiotherapy

ACTIVE COMPARATOR

Radiotherapy

Biological: bleomycin sulfate; Drug: dacarbazine; Drug: doxorubicin hydrochloride; Drug: vinblastine; Radiation: radiation therapy

ABVD Alone

ACTIVE COMPARATOR

ABVD Alone

Biological: bleomycin sulfate; Drug: dacarbazine; Drug: doxorubicin hydrochloride; Drug: vinblastine

Interventions

bleomycin sulfate BIOLOGICAL

10 units/m2

ABVD Alone; Radiotherapy or ABVD + Radiotherapy

dacarbazine DRUG

375mg/m2

ABVD Alone; Radiotherapy or ABVD + Radiotherapy

doxorubicin hydrochloride DRUG

25mg/m2

ABVD Alone; Radiotherapy or ABVD + Radiotherapy

vinblastine DRUG

6mg/m2

ABVD Alone; Radiotherapy or ABVD + Radiotherapy

radiation therapy RADIATION

35Gy in 20 fractions (daily)

Radiotherapy or ABVD + Radiotherapy

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

Eligibility Criteria * Histologically proven Hodgkin's Disease. A needle aspirate specimen will not be considered sufficient for diagnosis. * Pathologic material must have been reviewed by a designated local reference pathologist (LRP) prior to randomization. Histologic subtype determined by the LRP will be used for patient cohort assignment. * Patients must have clinical stage I - IIA disease according to Ann Arbor staging criteria. Clinical stage must be based on at least one tissue biopsy. The following aspects are to be considered in determining patient stage: i) Splenic Enlargement: Splenic enlargement determined by imaging studies only should not be considered evidence of splenic involvement with Hodgkin's disease. Patients should be considered as having splenic involvement if the spleen is palpable on physical examination and enlarged on imaging studies, or imaging studies show focal abnormalities consistent with Hodgkin's disease. These patients, if presenting with supradiaphragmatic disease would therefore be assessed as having Stage III disease and would be ineligible. ii) Bone Disease: Lytic or blastic lesions seen on plain radiographs or abnormalities on bone scan consistent with Hodgkin's disease will be considered as bone involvement with Hodgkin's disease. These patients would therefore be assessed as having Stage IV disease and would be ineligible. iii) Pleural Effusion and Ascites: The presence of a pleural effusion or ascites will be considered as evidence of Hodgkin's disease even if cytological examination is negative. These patients would be assessed as having probable Stage IV disease and therefore would be ineligible. Patients assessed on Xray as having pleural thickening or "blunting" of the costophrenic angle only may be eligible. iv) Extra-nodal vs. Stage IV Disease: Patients with disease involving a single extra-nodal site may be considered as "limited-stage" provided all disease can be included in a standard radiation field. Patients with extra-nodal disease that cannot be included in such a field (eg, lung, bone) or with multiple sites of extra-nodal disease are not eligible for this trial. * Pulmonary function tests must be done in patients with symptomatic lung disease. FVC, FEV-1 and DLCO must be ≥ 60% of predicted value. Patients with asthma controlled by medication are eligible if the above criteria are met. * Patient's age is ≥ 16 years. (Note that the lower age limit at each centre will be determined by that centre's policy regarding the age at which an individual may sign their own consent.) * Patient must not have received previous chemotherapy or radiotherapy. * Laboratory requirements: granulocytes ≥ 1.5 x 109/L (S.I.) or ≥ 1.5 x 103/uL (U.S.) platelets ≥ 125 x 109/L (S.I.) or ≥ 125 x 103/uL (U.S.) bilirubin ≤ 2.5 x UNL (unless due to hemolytic anemia) serum creatinine ≤ 2 x UNL * Patient must have been seen by both a radiation oncologist and medical oncologist who agree the patient is able to receive protocol radiation therapy. * Patient consent must be obtained according to local Institutional and/or University Human Experimentation Committee requirements. It will be the responsibility of the local participating investigators to obtain the necessary local clearance, and to indicate in writing to the NCIC CTG Clinical Trials Coordinator that such clearance has been obtained, before the trial can commence in that centre. Because of differing requirements, a standard consent form for the trial will not be provided but a sample form is given. The patient must sign the consent form prior to randomization. Please note that the consent form for this study must contain a statement which gives permission for the NCICCTG and monitoring agencies to review patient records. * Availability of patient for follow-up and quality of life (QoL) assessments. Patients must be accessible for treatment and follow-up. Investigators must assure themselves that patients registered on this trial will be available for complete documentation of the treatment, toxicity and follow-up. Comparison of quality of life is an end-point of this study. Patients must have completed the pre-randomization quality of life assessment and be willing to complete future assessments. The only exceptions will be patients who are unable to read english or french. Patients on study are expected to complete all the quality of life assessments but, should this not prove possible, they will be retained in the study for all other analyses. Ineligibility Criteria * Prior or concurrent malignancies, except adequately treated basal cell carcinoma of the skin. (Patients with prior carcinoma-in-situ of the cervix are not eligible.) * Cardiac disease defined as symptomatic congestive heart failure or coronary artery disease, known valvular (other than asymptomatic mitral valve prolapse) or congenital heart disease (other than asymptomatic atrial septal defects) or need for cardiac medications. Hypertension controlled with drug therapy is not an exclusion criterion. * Other major medical illness judged likely by the local investigator to preclude safe administration of protocol treatment or required follow-up. * Patients with stage IA disease (who might be treated with involved-field only irradiation) defined by meeting all of the following criteria: i) lymphocyte predominant or nodular sclerosing histology ii) disease bulk \< 3 cm iii) erythrocyte sedimentation rate (ESR) \< 50 iv) unilateral high - neck only disease, defined as disease located above the upper border of the thyroid cartilage or isolated epitrochlear adenopathy * Patients with very unfavourable clinical stage I-IIA disease defined as bulky adenopathy. Bulky adenopathy is defined as a palpable nodal mass greater than 10 cm. in diameter or a mediastinal mass with a maximum mass diameter measuring greater than or equal to 1/3 the maximum chest wall diameter (see Appendix III). * Patients with intra-abdominal disease. (Patients with pelvic disease: ileofemoral, inguinal or parailiac nodes are eligible for this study.) * Patients with B symptoms. * Patients known to have a positive antibody test for the human immunodeficiency virus (HIV) or who have a clinical diagnosis of acquired immunodeficiency syndrome. HIV testing is not a requirement for study entry. * Patients who have undergone a staging laparotomy. * Female patients who are pregnant. Note: men and women of childbearing age must be advised in the use of adequate contraception.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead
• Eastern Cooperative Oncology Group: collaborator

Study Sites (22)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Vancouver Island Cancer Centre

Victoria, British Columbia, V8R 6V5, Canada

Location

The Vitalite Health Network - Dr. Leon Richard

Moncton, New Brunswick, E1C 8X3, Canada

Location

Regional Health Authority B, Zone 2

Saint John, New Brunswick, E2L 4L2, Canada

Location

Dr. H. Bliss Murphy Cancer Centre

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Health Sciences North

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Trillium Health Partners - Credit Valley Hospital

Mississauga, Ontario, L5M 2N1, Canada

Location

Stronach Regional Health Centre at Southlake

Newmarket, Ontario, L3Y 2P9, Canada

Location

Lakeridge Health Oshawa

Oshawa, Ontario, L1G 2B9, Canada

Location

Algoma District Cancer Program

Sault Ste. Marie, Ontario, P6B 0A8, Canada

Location

Humber River Hospital

Toronto, Ontario, M3M 0B2, Canada

Location

Sinai Health System

Toronto, Ontario, M5G 1X5, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

CIUSSS de l'Est-de-I'lle-de-Montreal

Montreal, Quebec, H1T 2M4, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Instituto del Radio O. Alberti Spedali Civili

Brescia, 25123, Italy

Location

Policlinico Monteluce/Univ. Degli Studi Di Perugia

Perugia, 06122, Italy

Location

Royal South Hants Hospital

Southampton, SO14 0YG, United Kingdom

Location

Related Publications (6)

• Macdonald DA, Ding K, Gospodarowicz MK, Wells WA, Pearcey RG, Connors JM, Winter JN, Horning SJ, Djurfeldt MS, Shepherd LE, Meyer RM. Patterns of disease progression and outcomes in a randomized trial testing ABVD alone for patients with limited-stage Hodgkin lymphoma. Ann Oncol. 2007 Oct;18(10):1680-4. doi: 10.1093/annonc/mdm287. Epub 2007 Sep 10.

  PMID: 17846017 RESULT

• Macdonald DA, Gospodarowicz MK, Wells WA, et al.: Relapse patterns and subsequent outcomes of patients treated on the NCIC CTG HD.6 (ECOG JHD06) randomized trial evaluating ABVD alone in patients with limited stage Hodgkin's lymphoma (HL). [Abstract] Blood 106 (11): A-817, 2005.

  RESULT

• Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Bezjak A, Wells WA, Burns BF, Winter JN, Horning SJ, Dar AR, Djurfeldt MS, Ding K, Shepherd LE; National Cancer Institute of Canada Clinical Trials Group; Eastern Cooperative Oncology Group. Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group. J Clin Oncol. 2005 Jul 20;23(21):4634-42. doi: 10.1200/JCO.2005.09.085. Epub 2005 Apr 18.

  PMID: 15837968 RESULT

• Meyer R, Gospodarowicz M, Connors J, et al.: A randomized phase III comparison of single - modality ABVD with a strategy that includes radiation therapy in patients with early-stage Hodgkin's disease: the HD-6 trial of the National Cancer Institute of Canada Clinical Trials Group (Eastern Cooperative Oncology Group Trial JHD06). [Abstract] Blood 102 (11 Pt 1): A-81, 2003.

  RESULT

• Hay AE, Klimm B, Chen BE, Goergen H, Shepherd LE, Fuchs M, Gospodarowicz MK, Borchmann P, Connors JM, Markova J, Crump M, Lohri A, Winter JN, Dorken B, Pearcey RG, Diehl V, Horning SJ, Eich HT, Engert A, Meyer RM; Conducted by the NCIC Clinical Trials Group (Canada) and German Hodgkin Study Group (GHSG). An individual patient-data comparison of combined modality therapy and ABVD alone for patients with limited-stage Hodgkin lymphoma. Ann Oncol. 2013 Dec;24(12):3065-9. doi: 10.1093/annonc/mdt389. Epub 2013 Oct 11.

  PMID: 24121121 DERIVED

• Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Wells WA, Winter JN, Horning SJ, Dar AR, Shustik C, Stewart DA, Crump M, Djurfeldt MS, Chen BE, Shepherd LE; NCIC Clinical Trials Group; Eastern Cooperative Oncology Group. ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma. N Engl J Med. 2012 Feb 2;366(5):399-408. doi: 10.1056/NEJMoa1111961. Epub 2011 Dec 11.

  PMID: 22149921 DERIVED

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Bleomycin; Dacarbazine; Doxorubicin; Vinblastine; Radiotherapy

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Therapeutics

Study Officials

• Ralph M. Meyer, MD, FRCPC

  Margaret and Charles Juravinski Cancer Centre

  STUDY CHAIR

• Jane N. Winter, MD

  Robert H. Lurie Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: November 21, 2003
• Study Start: January 25, 1994
• Primary Completion: August 15, 2011
• Study Completion: January 6, 2012
• Last Updated: April 14, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (19); IT (2); GB (1)