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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00070304
First received: October 3, 2003
Last updated: July 25, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Lymphoma
Biological: filgrastim
Drug: gemcitabine hydrochloride
Drug: vinorelbine tartrate
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study Of Weekly Gemcitabine And Vinorelbine In Children With Recurrent Or Refractory Hodgkin's Disease

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Tumor Response Rate [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Adequate tumor response is defined as achieving CR, VGPR or PR at any evaluation.


Secondary Outcome Measures:
  • Toxicities [ Time Frame: Up to 4 weeks following the completion of therapy ] [ Designated as safety issue: Yes ]
    Toxic death, hepatic, cardiac or renal toxicity, hematologic toxicity, pulmonary toxicity or other grade 3 or 4 toxicities


Enrollment: 33
Study Start Date: July 2004
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
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
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.
Other Names:
  • Granulocyte Colony-Stimulating Factor
  • r-metHuG-CSF
  • G-CSF
  • Filgrastim
  • Neupogen
  • NSC # 614629
Drug: gemcitabine hydrochloride
Given IV over 100 minutes dose 1000 mg/m2/dose in 500 ml NS on days 1 and 8
Other Names:
  • Gemzar
  • NSC #613327
Drug: vinorelbine tartrate
Given IV over 6-10 minutes (central venous catheter). Dose 25 mg/m2/dose on days 1 and 8
Other Names:
  • Navelbine
  • NSC #608210

Detailed 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.

  Eligibility

Ages Eligible for Study:   up to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00070304

  Show 123 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Peter Cole, MD Rutgers Cancer Institute of New Jersey
  More Information

Additional Information:
Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00070304     History of Changes
Other Study ID Numbers: AHOD0321, CDR0000331915, COG-AHOD0321
Study First Received: October 3, 2003
Last Updated: July 25, 2013
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
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

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Gemcitabine
Lenograstim
Vinblastine
Vinorelbine
Adjuvants, Immunologic
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 29, 2014