Current Clinical Trials

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Drug combinations described in this section:

• ABVD: doxorubicin plus bleomycin plus vinblastine plus dacarbazine.
• BEACOPP: bleomycin plus etoposide plus doxorubicin plus cyclophosphamide plus vincristine plus procarbazine plus prednisone.
• COPP/ABVD: cyclophosphamide plus vincristine plus procarbazine plus prednisone/doxorubicin plus bleomycin plus vinblastine plus dacarbazine.
• MOPP: mechlorethamine plus vincristine plus procarbazine plus prednisone.
• MOPP alternating with ABVD: mechlorethamine plus vincristine plus procarbazine plus prednisone alternating with doxorubicin plus bleomycin plus vinblastine plus dacarbazine.
• MOPP/ABV hybrid: mechlorethamine plus vincristine plus procarbazine plus prednisone/doxorubicin plus bleomycin plus vinblastine.
• Stanford V: doxorubicin plus vinblastine plus mechlorethamine plus etoposide plus vincristine plus bleomycin plus prednisone.

Patients are designated as having advanced unfavorable Hodgkin lymphoma (HL) if they have clinical stage III or stage IV disease and four or more risk factors on the International Prognostic Index for HL, which corresponds to a freedom-from-progression at worse than 50% at 5 years with combination chemotherapy.[1]

ABVD therapy for 6 to 8 months is as effective as 12 months of MOPP alternating with ABVD, and both are superior to MOPP alone in terms of FFS (50% vs. 36% with a 14-year median follow-up; P = .03).[2,3][Level of evidence: 1iiA] The Intergroup trial comparing ABVD with MOPP/ABV hybrid showed equivalent efficacy in FFS and overall survival (OS), but increased toxic effects in the hybrid arm, especially from second malignancies.[4][Level of evidence: 1iiA]

The German Hodgkin Lymphoma Study Group randomly assigned 1,201 patients with advanced-stage disease to COPP/ABVD, BEACOPP, or to increased-dose BEACOPP, with most patients receiving consolidative radiation therapy to sites of initial bulky disease (≥5 cm).[5] The 5-year OS was 83% for COPP/ABVD, 88% for BEACOPP, and 91% for increased-dose BEACOPP (P = .16 for the comparison of COPP/ABVD with BEACOPP, P = .06 for the comparison of BEACOPP with increased-dose BEACOPP, and P = .002 for the comparison of COPP/ABVD with increased-dose BEACOPP).[5][Level of evidence: 1iiA] The actuarial rate of secondary acute leukemias 5 years after diagnosis of HL was 0.4% for COPP/ABVD, 0.6% for BEACOPP, and 2.5% for increased-dose BEACOPP (P = .03). Stanford V is an alternative drug combination currently under clinical evaluation with the Eastern Cooperative Oncology Group (ECOG) and the European Organization for Research and Treatment of Cancer (EORTC) in the ECOG-2496 and the EORTC-20012 trials, respectively.[6]

Three prospective randomized trials did not show a benefit in OS from the addition of consolidative radiation therapy to chemotherapy for patients with advanced-stage disease.[7-9][Level of evidence: 1iiA] In a meta-analysis of 1,740 patients treated on 14 different trials, no improvement was observed in 10-years' OS for patients with advanced-stage HL who received combined modality therapy versus chemotherapy alone.[10][Level of evidence: 3iiiA] No survival advantage is known for the use of radiation consolidation for patients with massive mediastinal disease and advanced stage, though differences exist in sites of first relapse.[11]

Clinical trials are addressing the role of more intensive regimens for patients with advanced-stage disease and poor prognostic factors. Controversy exists about whether the optimal strategy should involve early dose intensification, with subsequent risks of increased late toxic effects (such as leukemia) or whether ABVD should be employed and patients who relapse be salvaged with high-dose treatment and autografting. In a prospective randomized trial of 163 patients with unfavorable advanced-stage disease who attained a complete or partial remission after four cycles of ABVD, no difference was observed in OS or FFS either with high-dose therapy with autologous stem cell transplant or with four more cycles of ABVD.[12][Level of evidence: 1iiA]

Treatment options:

• ABVD for six to eight cycles.
• BEACOPP (increased dose).

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage III adult Hodgkin lymphoma and stage IV adult Hodgkin lymphoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

1. Hasenclever D, Diehl V: A prognostic score for advanced Hodgkin's disease. International Prognostic Factors Project on Advanced Hodgkin's Disease. N Engl J Med 339 (21): 1506-14, 1998.  [PUBMED Abstract]
   
   
2. Canellos GP, Anderson JR, Propert KJ, et al.: Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med 327 (21): 1478-84, 1992.  [PUBMED Abstract]
   
   
3. Canellos GP, Niedzwiecki D: Long-term follow-up of Hodgkin's disease trial. N Engl J Med 346 (18): 1417-8, 2002.  [PUBMED Abstract]
   
   
4. Duggan DB, Petroni GR, Johnson JL, et al.: Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: report of an intergroup trial. J Clin Oncol 21 (4): 607-14, 2003.  [PUBMED Abstract]
   
   
5. Diehl V, Franklin J, Pfreundschuh M, et al.: Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease. N Engl J Med 348 (24): 2386-95, 2003.  [PUBMED Abstract]
   
   
6. Federico M, Levis A, Luminari S, et al.: ABVD vs. STANFORD V (SV) vs. MOPP-EBV-CAD (MEC) in advanced Hodgkin's lymphoma. Final results of the IIL HD9601 randomized trial.. [Abstract] Proceedings of the American Society of Clinical Oncology 22 (Suppl 14): A-6507, 559s, 2004. 
   
   
7. Fabian CJ, Mansfield CM, Dahlberg S, et al.: Low-dose involved field radiation after chemotherapy in advanced Hodgkin disease. A Southwest Oncology Group randomized study. Ann Intern Med 120 (11): 903-12, 1994.  [PUBMED Abstract]
   
   
8. Aleman BM, Raemaekers JM, Tirelli U, et al.: Involved-field radiotherapy for advanced Hodgkin's lymphoma. N Engl J Med 348 (24): 2396-406, 2003.  [PUBMED Abstract]
   
   
9. Fermé C, Mounier N, Casasnovas O, et al.: Long-term results and competing risk analysis of the H89 trial in patients with advanced-stage Hodgkin lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte (GELA). Blood 107 (12): 4636-42, 2006.  [PUBMED Abstract]
   
   
10. Loeffler M, Brosteanu O, Hasenclever D, et al.: Meta-analysis of chemotherapy versus combined modality treatment trials in Hodgkin's disease. International Database on Hodgkin's Disease Overview Study Group. J Clin Oncol 16 (3): 818-29, 1998.  [PUBMED Abstract]
    
    
11. Brice P, Colin P, Berger F, et al.: Advanced Hodgkin disease with large mediastinal involvement can be treated with eight cycles of chemotherapy alone after a major response to six cycles of chemotherapy: a study of 82 patients from the Groupes d'Etudes des Lymphomes de l'Adulte H89 trial. Cancer 92 (3): 453-9, 2001.  [PUBMED Abstract]
    
    
12. Federico M, Bellei M, Brice P, et al.: High-dose therapy and autologous stem-cell transplantation versus conventional therapy for patients with advanced Hodgkin's lymphoma responding to front-line therapy. J Clin Oncol 21 (12): 2320-5, 2003.  [PUBMED Abstract]
    
    

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