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

Children's Oncology Group

Status and phase: Completed; Phase 2

Conditions: Lymphoma

Treatments: Drug: vinorelbine tartrate; Drug: gemcitabine hydrochloride; Biological: filgrastim

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00070304

AHOD0321

COG-AHOD0321 (Other Identifier)

CDR0000331915 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 33 patients

Sex: All

Ages: Under 30 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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33 participants in 1 patient group

Treatment

Experimental group

Description:

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.

Treatment:

Biological: filgrastim

Drug: gemcitabine hydrochloride

Drug: vinorelbine tartrate