Liposomal Vincristine in Treating Patients With Refractory or Relapsed Non-Hodgkin's Lymphoma

Pivotal Phase II Multicenter Study of Vincristine Sulfate Liposomes Injection in Diffuse Large B-Cell Non-Hodgkin's Lymphoma That is Refractory or Relapsed After Second-Line Combination Chemotherapy Revised Title Per 03/01 SR Pivotal Phase II Multicenter Study of Vincristine Sulfate Liposomes Injection in Aggressive Non-Hodgkin's Lymphoma That is Refractory to or Relapsed After Second-Line Combination Chemotherapy

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of liposomal vincristine in treating patients who have refractory or relapsed non-Hodgkin's lymphoma.

OBJECTIVES:

• Determine the complete and partial tumor responses in patients with aggressive non-Hodgkin's lymphoma that is refractory to or relapsed after second-line combination chemotherapy treated with vincristine sulfate liposomes injection.
• Determine the toxicity of this treatment regimen in these patients.
• Determine the duration of response, time to progression, and survival in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive vincristine sulfate liposomes IV over 1 hour. Treatment repeats every 2 weeks for a maximum of 12 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 8 weeks until disease progression.

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study within 1 year.

DISEASE CHARACTERISTICS:

• Histologically confirmed aggressive non-Hodgkin's lymphoma including:

  • Peripheral T-cell lymphoma not otherwise specified

  • Anaplastic large null-/T-cell lymphoma

  • Diffuse large B-cell lymphoma including:

    • Primary mediastinal large B-cell lymphoma with sclerosis
    • Intravascular large B-cell lymphoma
    • Immunoblastic B-cell lymphoma
    • T-cell-rich B-cell lymphoma
    • Anaplastic large B-cell lymphoma

• At least one bidimensionally measurable lesion with clearly defined margins at least 2 cm in the largest dimension by physical examination or CT scan

• No prior or active CNS lymphoma or AIDS-related lymphoma

• Must have received 2 or more prior chemotherapy courses from time of diagnosis of aggressive lymphoma or from time of biopsy-proven transformation from indolent to aggressive

  • Prior first and second-line therapy must have been combination chemotherapy
  • Prior first-line chemotherapy regimen must have contained anthracycline
  • Must have had at least a minor response to first-line therapy

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-3

Life expectancy:

• Not specified

Hematopoietic:

• Granulocyte count at least 500/mm^3 (unless due to lymphoma bone marrow involvement)
• Platelet count at least 50,000/mm^3 (unless due to lymphoma bone marrow involvement)

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• ALT no greater than 4 times ULN
• Alkaline phosphatase no greater than 4 times ULN

Renal:

• Not specified

Neurologic:

• No prior neurological disorders unrelated to chemotherapy (including familial neurological diseases or acquired demyelinating disorders)
• No neuromuscular impairment (neuromotor, neurosensory, or neurocerebellar)
• No prior grade 3 or 4 sensory or motor neuropathy related to chemotherapy

Other:

• No uncontrolled severe medical illness or infection
• HIV negative
• No other malignancies within the past 5 years except curatively resected basal cell skin cancer or carcinoma in situ of the cervix
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Radiotherapy
• No prior allogeneic bone marrow or peripheral blood stem cell transplantation
• At least 4 weeks since prior immunotherapy
• No concurrent biological agents

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy

Endocrine therapy:

• At least 4 weeks since prior corticosteroids at a dose greater than 10 mg/day of prednisone or equivalent

Radiotherapy:

• Prior involved-field radiotherapy allowed if irradiated area is not the only source of measurable disease
• Prior total body radiotherapy with high-dose therapy and autologous stem cell transplantation allowed
• At least 4 weeks since prior radiotherapy
• No concurrent radiotherapy to any disease site

Surgery:

• At least 4 weeks since prior major surgery except for diagnosis of lymphoma
• No concurrent surgical removal of any indicator lesion

Other:

• At least 4 weeks since prior alternative or investigational anticancer treatment
• No other concurrent systemic anticancer therapy
• No other concurrent investigational drug
• No concurrent phenytoin
• No concurrent hepatic drug metabolism inhibitors or inducers (cytochrome P450 isoenzymes in the CYP 3A subfamily)