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

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

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.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Biological: filgrastim; Drug: gemcitabine hydrochloride; Drug: vinorelbine tartrate

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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Perth, Western Australia, Australia, 6001
      • Princess Margaret Hospital for Children
• Canada
  • Quebec, Canada, G1V 4G2
    • Centre Hospitalier Universitaire de Quebec
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • University of Alberta Hospital
    • Sherbrooke, Alberta, Canada, J1H5N4
      • CHUS-Hopital Fleurimont
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • Children's & Women's Hospital of British Columbia
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 6R8
      • IWK Health Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster Children's Hospital at Hamilton Health Sciences
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Hospital for Sick Children
  • Quebec
    • Montreal, Quebec, Canada, H3H 1P3
      • Montreal Children's Hospital at McGill University Health Center
    • Montreal, Quebec, Canada, H3T 1C5
      • Hopital Sainte Justine
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre at the University of Saskatchewan
• Puerto Rico
  • Santurce, Puerto Rico, 00912
    • San Jorge Children's Hospital
• Switzerland
  • Geneva, Switzerland, 1205
    • Swiss Pediatric Oncology Group Geneva
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Lurleen Wallace Comprehensive Cancer at University of Alabama-Birmingham
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
  • California
    • Downey, California, United States, 90242-2814
      • Southern California Permanente Medical Group
    • Loma Linda, California, United States, 92354
      • Loma Linda University Cancer Institute at Loma Linda University Medical Center
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center at UCLA
    • Madera, California, United States, 93638-8762
      • Children's Hospital Central California
    • Sacramento, California, United States, 95825
      • Kaiser Permanente Medical Center - Oakland
    • San Diego, California, United States, 92123-4282
      • Children's Hospital and Health Center - San Diego
    • San Francisco, California, United States, 94115
      • UCSF Comprehensive Cancer Center
    • Stanford, California, United States, 94305
      • Stanford Comprehensive Cancer Center - Stanford
  • Connecticut
    • Farmington, Connecticut, United States, 06360-2875
      • Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
  • Delaware
    • Wilmington, Delaware, United States, 19899
      • Alfred I. DuPont Hospital for Children
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Lee Cancer Care of Lee Memorial Health System
    • Gainesville, Florida, United States, 32610-0232
      • University of Florida Shands Cancer Center
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic
    • Miami, Florida, United States, 33136
      • University of Miami Sylvester Comprehensive Cancer Center
    • Miami, Florida, United States, 33155
      • Miami Children's Hospital
    • Orlando, Florida, United States, 32803-1273
      • Florida Hospital Cancer Institute at Florida Hospital Orlando
    • Orlando, Florida, United States, 32806
      • Nemours Children's Clinic - Orlando
    • Pensacola, Florida, United States, 32504
      • Sacred Heart Cancer Center at Sacred Heart Hospital
    • St. Petersburg, Florida, United States, 33701
      • All Children's Hospital
    • Tampa, Florida, United States, 33607
      • St. Joseph's Cancer Institute at St. Joseph's Hospital
    • West Palm Beach, Florida, United States, 33407
      • Kaplan Cancer Center at St. Mary's Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute of Emory University
    • Savannah, Georgia, United States, 31403-3089
      • Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
  • Hawaii
    • Honolulu, Hawaii, United States, 95813
      • Cancer Research Center of Hawaii
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Children's Memorial Hospital - Chicago
    • Springfield, Illinois, United States, 62794-9620
      • Southern Illinois University School of Medicine
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5289
      • Indiana University Cancer Center
    • Indianapolis, Indiana, United States, 46260
      • St. Vincent Indianapolis Hospital
  • Iowa
    • Des Moines, Iowa, United States, 50309
      • Blank Children's Hospital
  • Kansas
    • Kansas City, Kansas, United States, 66160-7357
      • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0293
      • Markey Cancer Center at University of Kentucky Chandler Medical Center
    • Louisville, Kentucky, United States, 40232
      • Kosair Children's Hospital
  • Maine
    • Bangor, Maine, United States, 04401
      • CancerCare of Maine at Eastern Maine Medial Center
    • Scarborough, Maine, United States, 04074-9308
      • Maine Children's Cancer Program
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Baltimore, Maryland, United States, 21215
      • Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02111
      • Floating Hospital for Children at Tufts - New England Medical Center
    • Worcester, Massachusetts, United States, 01655
      • UMASS Memorial Cancer Center - University Campus
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0238
      • C.S. Mott Children's Hospital at University of Michigan Medical Center
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Grand Rapids, Michigan, United States, 49503-2560
      • Spectrum Health Hospital - Butterworth Campus
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Van Elslander Cancer Center at St. John Hospital and Medical Center
    • Lansing, Michigan, United States, 48910
      • Breslin Cancer Center at Ingham Regional Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical Center & Children's Hospital - Fairview
    • Minneapolis, Minnesota, United States, 55404
      • Children's Hospitals and Clinics of Minneapolis
  • Mississippi
    • Jackson, Mississippi, United States, 39216-4505
      • University of Mississippi Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
    • St. Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center Cancer Center
    • Livingston, New Jersey, United States, 07039
      • St. Barnabas Medical Center Cancer Center
    • Morristown, New Jersey, United States, 07962
      • Overlook Hospital
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-5636
      • University of New Mexico Cancer Research and Treatment Center
  • New York
    • Albany, New York, United States, 12208-3419
      • Albany Medical Center Hospital
    • Bronx, New York, United States, 10461
      • Albert Einstein Cancer Center at Albert Einstein College of Medicine
    • Brooklyn, New York, United States, 11201-5493
      • Brooklyn Hospital Center
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10032
      • Herbert Irving Comprehensive Cancer Center at Columbia University
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University Hospital
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • North Carolina
    • Charlotte, North Carolina, United States, 28232-2861
      • Blumenthal Cancer Center at Carolinas Medical Center
    • Charlotte, North Carolina, United States, 28233-3549
      • Presbyterian Cancer Center at Presbyterian Hospital
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center
  • Ohio
    • Akron, Ohio, United States, 44308-1062
      • Children's Hospital Medical Center of Akron
    • Cincinnati, Ohio, United States, 45229-3039
      • Cincinnati Children's Hospital Medical Center
    • Cleveland, Ohio, United States, 44106-5000
      • Rainbow Babies and Children's Hospital
    • Cleveland, Ohio, United States, 44195-5217
      • Cleveland Clinic Taussig Cancer Center
    • Dayton, Ohio, United States, 45404-1815
      • Children's Medical Center - Dayton
    • Youngstown, Ohio, United States, 44501
      • Tod Children's Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Cancer Institute
  • Oregon
    • Portland, Oregon, United States, 97227
      • Legacy Emanuel Hospital and Health Center & Children's Hospital
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822-0001
      • Geisinger Medical Center
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Cancer Institute at Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19134-1095
      • St. Christopher's Hospital for Children
    • Philadelphia, Pennsylvania, United States, 19104-9786
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15213
      • Children's Hospital of Pittsburgh
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital Comprehensive Cancer Center
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Hospital System Cancer Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57117-5039
      • Sioux Valley Hospital and University of South Dakota Medical Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • T.C. Thompson Children's Hospital
    • Knoxville, Tennessee, United States, 37916
      • East Tennessee Children's Hospital
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
    • Nashville, Tennessee, United States, 37232-6310
      • Vanderbilt-Ingram Cancer Center
  • Texas
    • Amarillo, Texas, United States, 79106
      • Texas Tech University Health Sciences Center School of Medicine - Amarillo
    • Corpus Christi, Texas, United States, 78466
      • Driscoll Children's Hospital
    • Dallas, Texas, United States, 75230
      • Medical City Dallas Hospital
    • Dallas, Texas, United States, 75390
      • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
    • Fort Worth, Texas, United States, 76104-9958
      • Cook Children's Medical Center - Fort Worth
    • Houston, Texas, United States, 77030-2399
      • Baylor University Medical Center - Houston
    • Lubbock, Texas, United States, 79410
      • Covenant Children's Hospital
    • San Antonio, Texas, United States, 78229-3993
      • Methodist Children's Hospital of South Texas
    • San Antonio, Texas, United States, 78207
      • University of Texas Health Science Center at San Antonio
    • Temple, Texas, United States, 76508
      • CCOP - Scott and White Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84113-1100
      • Primary Children's Medical Center
  • Virginia
    • Norfolk, Virginia, United States, 23507-1971
      • Children's Hospital of The King's Daughters
  • Washington
    • Spokane, Washington, United States, 99220-2555
      • Providence Cancer Center at Sacred Heart Medical Center
    • Tacoma, Washington, United States, 98405
      • Mary Bridge Children's Hospital and Health Center - Tacoma
    • Tacoma, Washington, United States, 98431
      • Madigan Army Medical Center - Tacoma
  • West Virginia
    • Charleston, West Virginia, United States, 25302
      • West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54307-3508
      • St. Vincent Hospital Regional Cancer Center
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic - Marshfield Center
    • Milwaukee, Wisconsin, United States, 53226
      • Midwest Children's Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 30 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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: G-CSF; Granulocyte Colony-Stimulating Factor; r-metHuG-CSF; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Peter Cole, MD, Rutgers Cancer Institute of New Jersey

Publications and helpful links

General Publications

• Cole PD, McCarten KM, Drachtman RA, Alarcon Pd, Chen L, Trippett TM, Schwartz CL. Early [(1)(8)F]fluorodeoxyglucose positron emission tomography-based response evaluation after treatment with gemcitabine and vinorelbine for refractory Hodgkin disease: a children's oncology group report. Pediatr Hematol Oncol. 2010 Nov;27(8):650-7. doi: 10.3109/08880018.2010.504250.
• Cole PD, Schwartz CL, Drachtman RA, de Alarcon PA, Chen L, Trippett TM. Phase II study of weekly gemcitabine and vinorelbine for children with recurrent or refractory Hodgkin's disease: a children's oncology group report. J Clin Oncol. 2009 Mar 20;27(9):1456-61. doi: 10.1200/JCO.2008.20.3778. Epub 2009 Feb 17.
• Cole PD, Trippett TM, Drachtman RA: AHOD0321: a COG phase 2 study of weekly gemcitabine and vinorelbine for children with recurrent or refractory Hodgkin disease. [Abstract] Blood 110 (11): A-2318, 2007.

Study record dates

Study Major Dates

• Study Start: July 1, 2004
• Primary Completion (Actual): September 1, 2007

Study Registration Dates

• First Submitted: October 3, 2003
• First Submitted That Met QC Criteria: October 6, 2003
• First Posted (Estimate): October 7, 2003

Study Record Updates

• Last Update Posted (Estimate): July 26, 2013
• Last Update Submitted That Met QC Criteria: July 25, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: 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: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Adjuvants, Immunologic; Gemcitabine; Lenograstim; Vinorelbine
• Other Study ID Numbers: AHOD0321; CDR0000331915 (Other Identifier: Clinical Trials.gov); COG-AHOD0321 (Other Identifier: Children's Oncology Group)