Gemcitabine and Vinorelbine in Treating Young Patients With Recurrent or Refractory Hodgkin's Lymphoma

OBJECTIVES:

• Determine the response rate of pediatric patients with recurrent or refractory Hodgkin's lymphoma treated with gemcitabine and vinorelbine.
• Determine the toxicity of this regimen in these patients.

OUTLINE: This is a nonrandomized, multicenter study.

Patients receive vinorelbine IV over 6-10 minutes and gemcitabine IV over 100 minutes on days 1 and 8. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 9 and continuing for at least 7 days and until blood counts recover. Treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients with responding disease after 2 courses may proceed directly to stem cell transplantation off study OR receive 2 additional courses. Patients with stable disease after 2 courses receive at least 2 additional courses. Patients with continued stable or responding disease (with no disease progression) after 4 courses may continue to receive study treatment for up to 1 year or discontinue study for alternative therapy at the discretion of the treating physician.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 13-26 patients will be accrued for this study within 1.5 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed Hodgkin's lymphoma* with any of the following histologies:

• Not otherwise specified (NOS)
• Mixed cellularity NOS
• Lymphocytic depletion

• NOS
• Diffuse fibrosis
• Reticular
• Lymphocytic predominance

• NOS
• Diffuse
• Nodular
• Paragranuloma
• Granuloma
• Sarcoma
• Nodular sclerosis

• Cellular phase
• NOS
• Lymphocytic predominance
• Mixed cellularity
• Lymphocytic depletion NOTE: *Disease metastatic to bone marrow with granulocytopenia and/or thrombocytopenia is allowed, but is not evaluable for hematological toxicity
• Measurable disease by clinical or radiographic criteria
• Relapsed or refractory to conventional therapy

• Received at least 2 prior cytotoxic chemotherapy regimens
• No stage IA or IIA nodal disease previously treated with any of the following:

• Radiotherapy only
• No more than 4 courses of prior chemotherapy

PATIENT CHARACTERISTICS:

Age

• 30 and under

Performance status

• Karnofsky 50-100% (over 16 years of age)
• Lansky 50-100% (16 and under) OR
• ECOG 0-2

Life expectancy

• At least 8 weeks

Hematopoietic

• See Disease Characteristics
• Absolute neutrophil count ≥ 750/mm^3
• Platelet count ≥ 75,000/mm^3 (transfusion independent, defined as ≥ 3 days since prior platelet transfusion)

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT ≤ 2.5 times ULN

Renal

• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR
• Creatinine based on age as follows:

• No greater than 0.8 mg/dL (age 5 and under)
• No greater than 1.0 mg/dL (age 6 to 10)
• No greater than 1.2 mg/dL (age 11 to 15)
• No greater than 1.5 mg/dL (over age 15)

Pulmonary

• DLCO ≥ 50%
• FEV_1 ≥ 50%
• Vital capacity ≥ 50%
• No evidence of dyspnea at rest
• No exercise intolerance

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation
• Seizure disorder allowed provided patient is on anticonvulsants and disorder is well controlled
• No evidence of active graft-versus-host disease

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Recovered from prior immunotherapy
• At least 6 months since prior allogeneic stem cell transplantation (SCT)
• At least 7 days since prior biologic agents
• More than 3 months since prior autologous SCT
• More than 1 week since prior growth factors
• No concurrent immunomodulating agents

Chemotherapy

• See Disease Characteristics
• More than 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered
• No prior gemcitabine and vinorelbine in combination (i.e., administered within 1 week of each other)

• Prior gemcitabine or vinorelbine administered alone is allowed
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent steroids, including corticosteroids as an antiemetic or for control of graft-versus-host disease

• Concurrent corticosteroids allowed only for the following indications:

• Adrenal crisis in patients with suppressed pituitary/adrenal response
• Noncardiogenic pulmonary edema
• Allergic reactions to amphotericin or transfusions treated with low-dose hydrocortisone (less than 100 mg/m^2)

Radiotherapy

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy and recovered

Surgery

• Not specified

Other

• Concurrent immunosuppressive drugs allowed