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Phase 3
16 Years
Not Enrolling
Hodgkin Lymphoma

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Trial Information


OBJECTIVES: I. Compare the 12-year survival of patients with clinical stage I-IIA Hodgkin's
disease treated with radiotherapy with or without doxorubicin, bleomycin, vinblastine, and
dacarbazine (ABVD) versus ABVD only. II. Compare the freedom from progression at 5 and 10
years in patients treated with these regimens. III. Compare the complete remission rate,
freedom from secondary disease progression at 5 and 10 years, and cause-specific survival at
5, 10, and 15 years in patients treated with these regimens. IV. Compare the short- and
long-term toxicity of these regimens in these patients. V. Compare the quality of life of
patients in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by center.
Patients who are under age 40 and have lymphocyte-predominant or nodular sclerosing
histology, an erythrocyte sedimentation rate less than 50, and fewer than 4 disease sites
(supradiaphragmatic or pelvic node sites) are assigned to cohort 1 (good prognosis). All
other patients are assigned to cohort 2 (poor prognosis). Cohort 1: Arm I: Patients with
supradiaphragmatic disease undergo radiotherapy to the supradiaphragmatic lymph node areas
(mantle region), spleen, and para-aortic lymph nodes 5 days a week for 4 weeks. Patients
with pelvic disease undergo radiotherapy to an "inverted-Y" field (excluding the spleen) 5
days a week for 4 weeks. Arm II: Patients receive doxorubicin, bleomycin, vinblastine, and
dacarbazine IV on days 1 and 15 (ABVD). Treatment continues every 4 weeks for a total of 2
courses in the absence of disease progression or unacceptable toxicity. Patients with
complete remission (CR) after course 2 receive 2 additional courses past CR. Patients with
partial remission (PR) after course 2 receive 4 additional courses past PR. Patients with
unconfirmed/uncertain complete remission (CRu) receive 2-4 additional courses past CRu.
Cohort 2: Arm III: Patients receive ABVD as in arm II, followed 4-6 weeks later by
concurrent radiotherapy to the mantle region and upper abdomen to the level of L2 5 days a
week for 4 weeks. Alternatively, radiotherapy may also be administered sequentially to the
mantle region 5 days a week for 4 weeks and then to the upper abdomen to the level of L2 5
days a week for 4 weeks. Arm IV: Patients receive ABVD only as in arm II. Patients with
disease progression after treatment in arms II or IV are considered for radiotherapy.
Quality of life is assessed on day 1 of each course of chemotherapy (arms II-IV) and on day
28 of the last course of chemotherapy (arms II and IV); on the first and final days of
radiotherapy (arms I and III); at 4 weeks and at 3, 6, and 12 months after completion of
radiotherapy (arms I and III) or chemotherapy (arms II and IV); and then annually for 2-10
years. Patients are followed at months 3, 6, and 12 and then annually thereafter.

PROJECTED ACCRUAL: A total of 450 patients will be accrued for this study within 7.5 years.

Inclusion Criteria

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.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:


Outcome Description:

12 year survival comparison

Outcome Time Frame:

12 years

Safety Issue:


Principal Investigator

Ralph M. Meyer, MD, FRCPC

Investigator Role:

Study Chair

Investigator Affiliation:

Margaret and Charles Juravinski Cancer Centre


Canada: Health Canada

Study ID:




Start Date:

January 1994

Completion Date:

January 2012

Related Keywords:

  • Hodgkin Lymphoma
  • 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
  • Hodgkin Disease
  • Lymphoma