Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage I or Stage II Hodgkin's Lymphoma

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 2

Conditions: Lymphoma

Treatments: Drug: gemcitabine hydrochloride; Procedure: CT scan; Procedure: fludeoxyglucose F 18 positron-emission tomography (PET) scan; Drug: vinblastine; Drug: doxorubicin hydrochloride

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00086801

CDR0000370870 (Registry Identifier)

CALGB-50203

U10CA031946 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as doxorubicin, vinblastine, and gemcitabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: This phase II trial is studying how well combination chemotherapy works in treating patients with newly diagnosed stage I or stage II Hodgkin's lymphoma.

Full description

OBJECTIVES:

Primary

• Determine the complete response rate in patients with newly diagnosed stage IA, IB, IIA, or IIB non-bulky Hodgkin's lymphoma treated with doxorubicin, vinblastine, and gemcitabine.

Secondary

• Determine the event-free survival of patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.
• Determine whether fludeoxyglucose F 18 positron-emission tomography scanning is useful in predicting clinical relapse and determining the presence of residual disease in these patients after treatment with this regimen.

OUTLINE: This is a multicenter study.

Patients receive doxorubicin IV over 3-5 minutes, vinblastine IV over 3-5 minutes, and gemcitabine IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo fludeoxyglucose F 18 positron-emission tomography (PET) scanning and CT scan before treatment and after courses 2 and 6 of therapy to assess response. Patients with a positive PET scan after completion of study therapy may undergo biopsy. A PET scan is performed 3 months later if biopsy is negative or biopsy is unable to be performed.

Patients are followed every 3 months for 1 year, every 4 months for 2 years, every 6 months for 2 years, and then annually for 5 years.

Enrollment: 104 patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

1. Documentation of Disease:

   1.1 Histologically documented Hodgkin lymphoma subclassified according to the WHO modification of the Rye Classification and staged according to the modified Ann Arbor Staging Classification system. Patients must have clinical stage IA, IB, IIA or IIB. Patients with "E" extensions will be eligible if all other criteria have been met. Nodular lymphocyte predominant Hodgkin lymphoma is excluded.

   • Core biopsies are acceptable if they contain adequate tissue for primary diagnosis and immunophenotyping. Fine needle aspirate (FNA) cytologies and bone marrow biopsies as the sole means of diagnosis are not acceptable.
   • Note: Failure to submit pathology slides within 60 days of patient registration will result in patient being declared ineligible.

   1.2 Patients may not have a mediastinal mass > 0.33 maximum intrathoracic diameter on standing postero-anterior chest x-ray or peripheral or retroperitoneal adenopathy > 10 cm in its largest diameter.

   1.3 Bone marrow biopsy is required for pretreatment evaluation. Bilateral biopsies are preferred but not required.

2. No prior treatment (chemotherapy or radiation therapy) for Hodgkin lymphoma.

3. Measurable disease must be present either on physical examination or imaging studies. Any tumor mass measurable in two dimensions and > 2 cm is acceptable (or 1.5 cm if 0.5 cm slices are used as in spiral CT scans). Lesions that are considered intrinsically non-measurable include the following:

   • bone lesions
   • leptomeningeal disease
   • ascites
   • pleural/pericardial effusion
   • inflammatory breast disease
   • lymphangitis cutis/pulmonis
   • abdominal masses that are not confirmed and followed by imaging techniques
   • cystic lesions
   • lesions that are situated in a previously irradiated area

4. Age ≥ 16 years

5. Performance status 0-2

6. LVEF by ECHO or MUGA within institutional normal limits

7. DLCO ≥ 60% with no symptomatic pulmonary disease

8. No known HIV infection. Patients with a history of intravenous drug abuse or any behavior associated with an increased risk of HIV infection should be tested for exposure to the HIV virus. Patients who test positive or who are known to be infected are not eligible due to an increased risk of infection with this chemotherapy regimen. An HIV test is not required for entry on this protocol, but is required if the patient is perceived to be at risk.

9. Non-pregnant and non-lactating. Due to the teratogenic potential of the agents used in this study, pregnant or nursing women may not be enrolled. Women and men of reproductive potential should agree to use an effective means of birth control.

10. Initial Required Laboratory Data:

    • ANC ≥ 1000/μL
    • Platelet count ≥ 100,000/μL
    • Serum Creatinine ≤ 2 mg/dL
    • Bilirubin ≤ 2 mg/dL
    • AST ≤ 2 x upper limit of normal

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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104 participants in 1 patient group

doxorubicin + vinblastine + gemcitabine

Experimental group

Description:

Patients receive doxorubicin IV over 3-5 minutes, vinblastine IV over 3-5 minutes, and gemcitabine IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients undergo fludeoxyglucose F 18 positron-emission tomography (PET) scanning and CT scan before treatment and after courses 2 and 6 of therapy to assess response. Patients with a positive PET scan after completion of study therapy may undergo biopsy. A PET scan is performed 3 months later if biopsy is negative or biopsy is unable to be performed. Patients are followed every 3 months for 1 year, every 4 months for 2 years, every 6 months for 2 years, and then annually for 5 years.

Treatment:

Drug: gemcitabine hydrochloride

Drug: doxorubicin hydrochloride

Procedure: fludeoxyglucose F 18 positron-emission tomography (PET) scan

Procedure: CT scan

Drug: vinblastine