Combination Chemotherapy in Treating Patients With Relapsed or Refractory Hodgkin's Lymphoma

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy in treating patients who have relapsed or refractory Hodgkin's lymphoma.

OBJECTIVES:

• Determine the maximum tolerated dose and toxicity of gemcitabine, vinorelbine, and doxorubicin HCl liposome in patients with relapsed or refractory Hodgkin's lymphoma.
• Determine the complete and partial response rates of patients treated with this regimen.

OUTLINE: This is a dose-escalation, multicenter study.

Phase I:

• Patients receive vinorelbine IV over 6-10 minutes, gemcitabine IV over 30 minutes, and doxorubicin HCl liposome IV over 30-60 minutes on days 1 and 8. Treatment continues every 21 days for 2-6 courses in the absence of unacceptable toxicity or disease progression. Patients who respond to treatment after 2 or more courses may stop protocol therapy to undergo peripheral blood stem cell transplantation.

Cohorts of 3-6 patients receive escalating doses of vinorelbine, gemcitabine, and doxorubicin HCl liposome until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive treatment with gemcitabine, vinorelbine, and doxorubicin HCl liposome at the recommended phase II dose.

Phase II:

• Patients are assigned to 1 of 2 treatment groups.

  • Group 1: Patients who have not undergone prior transplantation receive vinorelbine, gemcitabine, and doxorubicin HCl liposome as in phase I.
  • Group 2: Patients who have undergone prior transplantation receive lower doses of vinorelbine, gemcitabine, and doxorubicin HCl liposome as in group 1.

Patients are followed every 6 months for 2 years and then annually for 6 years.

PROJECTED ACCRUAL: Approximately 3-100 patients (3-42 for phase I and 20-58 for phase II [29 per group]) will be accrued for this study within 3 years.

• Drug: gemcitabine hydrochloride
• Drug: pegylated liposomal doxorubicin hydrochloride
• Drug: vinorelbine tartrate

• Lai R, Bartlett NL, Mackey JR, Jung SH, Johnson JL, Cook JR, Jones D, Cass CE, Young JD, Said J, Cheson B, Hsi ED. High expression of nucleoside transporter protein hENT1 in Reed-Sternberg cells is associated with treatment failure in relapsed/refractory Hodgkin lymphoma patients treated with gemcitabine, vinorelbine and liposomal doxorubicin - A CALGB 59804 correlative study. Leuk Lymphoma. 2008 Apr 30;:1-4 [Epub ahead of print] No abstract available.
• Bartlett N, Niedzwiecki D, Johnson J, Friedberg J, Johnson K, van Besien K, Zelenetz A, Cheson B, Canellos G. Gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD), a salvage regimen in relapsed Hodgkin's lymphoma: CALGB 59804. Ann Oncol. 2007 Apr 10; [Epub ahead of print]
• Bartlett N, Niedzwiecki D, Johnson J, et al.: A phase I/II study of gemcitabine, vinorelbine, and liposomal doxorubicin for relapsed Hodgkin's disease: preliminary results of CALGB 59804. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-2275, 566, 2003.

DISEASE CHARACTERISTICS:

• Histologically confirmed Hodgkin's lymphoma that is recurrent or refractory after standard chemotherapy

  • Core biopsy is acceptable if adequate tissue is obtained for primary diagnosis and immunophenotyping
  • Bone marrow biopsy is not acceptable as sole means of diagnosis

• Measurable disease

  • Tumor mass greater than 1 cm

PATIENT CHARACTERISTICS:

Age:

• Any age

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 2.0 mg/dL unless history of Gilbert's disease
• AST no greater than 2 times upper limit of normal

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• LVEF at least 45% by MUGA (for patients whose lifetime cumulative doxorubicin dose exceeds 400 mg/m^2)

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• See Cardiovascular
• No prior gemcitabine, vinorelbine, or doxorubicin HCl liposome
• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent hormones except for nondisease-related conditions (e.g., insulin for diabetes) or steroids for adrenal failure
• No concurrent dexamethasone or other steroidal antiemetics

Radiotherapy:

• Not specified

Surgery:

• Not specified