Comparison of Two Combination Chemotherapy Regimens With Either Vincristine or Vinblastine in Treating Patients With Advanced Anaplastic Large Cell Lymphoma

OBJECTIVES:

• Compare the efficacy of a consolidation chemotherapy regimen comprising doxorubicin and prednisone in combination with vincristine vs vinblastine, in terms of event-free survival, in patients with advanced anaplastic large cell lymphoma.

• Compare overall survival of patients treated with these regimens.

• Compare the toxic effects of these regimens in these patients.

• Correlate biological tumor characteristics and outcome in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study.

Patients are randomized at enrollment to receive either Standard APO regimen or a consolidation regimen including vinblastine (VBL).

• Induction therapy: All Patients receive doxorubicin IV over 15 minutes on days 1 and 22; vincristine IV on days 1, 8, 15, 22, and 29; oral prednisone 3 times daily on days 1-28; and intrathecal (IT) methotrexate on days 1, 8, and 22 (patients with central nervous system (CNS) disease at diagnosis receive additional methotrexate IT on days 15, 29, and 36).

Patients undergo restaging after Induction such that consolidation therapy is started on day 43. All patients with complete response (CR), complete response unconfirmed (CRu) or partial response (PR) proceed to Consolidation based on CT or MRI scans at the end of induction (week 6). All other patients will be removed from protocol therapy and will be followed until they meet the criteria for off study. Follow-up data will be required unless consent is withdrawn.

• Standard APO (Arm I): Patients receive course-specific regimens without vinblastine.

  • Courses 1-3: Patients receive doxorubicin IV over 15 minutes, vincristine IV, and methotrexate IT on day 1 and oral prednisone three times daily and oral mercaptopurine once daily on days 1-5.

  • Courses 4-5: Patients receive doxorubicin, vincristine, prednisone, and mercaptopurine as in courses 1-3.

  • Courses 6-15: Patients receive vincristine, prednisone, and mercaptopurine as in courses 1-3 and methotrexate IV on day 1.

• Consolidation with vinblastine (Arm II): Patients receive course-specific regimens including vinblastine.

  • Courses 1-3: Patients receive doxorubicin, methotrexate IT, prednisone, and mercaptopurine as in arm I and vinblastine IV over 1 minute on days 1, 8, and 15.

  • Courses 4-5: Patients receive doxorubicin, prednisone, and mercaptopurine as in arm I and vinblastine as in arm II (courses 1-3).

  • Courses 6-15: Patients receive prednisone and mercaptopurine as in arm I, vinblastine as in arm II (courses 1-3), and methotrexate IV on day 1.

In both arms and all courses, treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed monthly for 1 year, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 200-250 patients (100-125 per treatment arm) will be accrued for this study within 5 years.