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

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as gemcitabine and vinorelbine, use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving gemcitabine together with vinorelbine works in treating young patients with recurrent or refractory Hodgkin's lymphoma.

Detailed Description
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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.

Official Title
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A Phase II Study Of Weekly Gemcitabine And Vinorelbine In Children With Recurrent Or Refractory Hodgkin's Disease

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: filgrastim
* Drug: gemcitabine hydrochloride
* Drug: vinorelbine tartrate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Patients receive vinorelbine tartrate IV over 6-10 minutes and gemcitabine hydrochloride 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. | Biological: filgrastim<br>* Given by mouth or IV, 5 micrograms/kg/dose (up to 10 micrograms/kg/dose) daily starting on day 9 for a minimum of 7 days and until the ANC is greater to or equal to 1,500/uL.<br>* Other names: NSC # 614629;Drug: gemcitabine hydrochloride<br>* Given IV over 100 minutes dose 1000 mg/m2/dose in 500 ml NS on days 1 and 8<br>* Other names: NSC #613327;Drug: vinorelbine tartrate<br>* Given IV over 6-10 minutes (central venous catheter). Dose 25 mg/m2/dose on days 1 and 8<br>* Other names: NSC #608210;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response Rate | Adequate tumor response is defined as achieving CR, VGPR or PR at any evaluation. | Up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicities | Toxic death, hepatic, cardiac or renal toxicity, hematologic toxicity, pulmonary toxicity or other grade 3 or 4 toxicities | Up to 4 weeks following the completion of therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent/refractory childhood Hodgkin lymphoma, childhood lymphocyte predominant Hodgkin lymphoma, childhood lymphocyte depletion Hodgkin lymphoma, childhood nodular sclerosis Hodgkin lymphoma, childhood mixed cellularity Hodgkin lymphoma