Reduced Duration Stanford V Chemotherapy With or Without Low-Dose Tailored-Field Radiation Therapy For Favorable Risk Pediatric Hodgkin Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by St. Jude Children's Research Hospital
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00846742
First received: February 17, 2009
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

This phase II trial is studying how well combination chemotherapy with or without radiation therapy works in treating young patients with favorable-risk Hodgkin lymphoma. Drugs used in chemotherapy, such as doxorubicin hydrochloride, vinblastine, mechlorethamine hydrochloride, vincristine sulfate, bleomycin, etoposide, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Radiation therapy uses high-energy x-rays to kill cancer cells for those patients that still had residual cancer at the end of chemotherapy. Giving combination chemotherapy with radiation therapy may kill more cancer cells and allow doctors to save the part of the body where the cancer started.


Condition Intervention Phase
Hodgkin Lymphoma
Drug: Stanford V Chemotherapy
Radiation: Radiation Therapy
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: Reduced Duration Stanford V Chemotherapy With or Without Low-Dose Tailored-Field Radiation Therapy For Favorable Risk Pediatric Hodgkin Lymphoma

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • Proportion of patients that will not require any radiotherapy by at least 20% more compared to the favorable risk arm in HOD99 [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    A 95% confidence interval of the complete response (CR) rate will be provided.


Secondary Outcome Measures:
  • Disease failure rate within radiation fields [ Time Frame: median 2 year post therapy ] [ Designated as safety issue: No ]
    Defined as disease that recurs in the initially involved nodal region within the field of irradiation. The disease failure rate within the radiation fields will be estimated with a 95% confidence interval using appropriate methods (e.g., estimate cumulative incidence in the presence of competing risks).

  • Treatment failure patterns for children treated with tailored-field radiation [ Time Frame: median 2 years post therapy ] [ Designated as safety issue: No ]
    Descriptive statistics related to local/distant failure will be produced. The cumulative incidence of local failure will be estimated and effects of prognostic factors will be examined. Effect of competing risks (distant failure, second malignancy and death) will be taken into account. Relapse rate within the radiation fields will be estimated and confidence interval will also be calculated.

  • Acute hematologic and infectious toxicity incidents as assessed by CTCAE version 3.0 [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Comparison of event-free and overall survival distributions, cumulative incidence of local failure, and toxicities of patients treated on this study to outcome and toxicities in the favorable risk group of HOD99 [ Time Frame: median 2 years post therapy ] [ Designated as safety issue: No ]
    Log-rank tests used to compare event-free survival and overall survival. Event-free survival is defined as time interval from the date of study enrollment to the date of first event (relapsed or progressive disease, second malignancy, or death from any cause) or to last follow-up for patients without events. Survival is defined as time interval from study enrollment to date of death from any cause or to date of last follow-up. Gray's test used to compare cumulative incidence of local failure between favorable risk patients treated on this protocol vs. treated on HOD99 and other regimens.

  • Comparison of event-free survival distributions between patients that will not be prescribed radiotherapy after 8 weeks Stanford V and those patients on HOD99 that received VAMP without radiotherapy [ Time Frame: median 2 years post therapy ] [ Designated as safety issue: No ]
    Log-rank tests used to compare event-free survival and overall survival. Event-free survival is defined as time interval from the date of study enrollment to the date of first event (relapsed or progressive disease, second malignancy, or death from any cause) or to last follow-up for patients without events. Survival is defined as time interval from study enrollment to date of death from any cause or to date of last follow-up. Gray's test used to compare cumulative incidence of local failure between favorable risk patients treated on this protocol vs. treated on HOD99 and other regimens.

  • Event-free survival distributions of favorable risk patients treated with Stanford V chemotherapy alone and patients treated with Stanford V chemotherapy plus low dose tailored-field radiation [ Time Frame: median 2 years post therapy ] [ Designated as safety issue: No ]
    Event-free survival distributions of favorable risk patients treated with Stanford V chemotherapy alone and patients treated with Stanford V chemotherapy plus low dose tailored field radiation will be estimated by the Kaplan-Meier method.


Estimated Enrollment: 64
Study Start Date: February 2009
Estimated Study Completion Date: July 2026
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
Participants receive Stanford V Chemotherapy with or without radiation therapy. Patients receive doxorubicin hydrochloride IV and vinblastine IV on day 1 of weeks 1, 3, 5, and 7; mechlorethamine hydrochloride IV on day 1 of weeks 1 and 5; vincristine sulfate IV and bleomycin IV on day 1 of weeks 2, 4, 6, and 8; etoposide IV on day 1 of weeks 3 and 7; and prednisone PO three times 2-3 weeks after completion of chemotherapy, patients not achieving complete response undergo radiation therapy to individual nodal sites (tailored fields)
Drug: Stanford V Chemotherapy
The Stanford V regimen is an abbreviated, multi-agent, dose-intensive regimen that utilizes many of the most active chemotherapy agents for Hodgkin lymphoma: Vinblastine, Doxorubicin, Vincristine, Bleomycin, Mechlorethamine, Etoposide, and Prednisone
Radiation: Radiation Therapy
Patients who achieve less than a complete response after 8 weeks of chemotherapy will receive 25.5 Gy to individual nodal sites (tailored fields) starting 2-3 weeks following completion of all chemotherapy and recovery of ANC to at least 1000.

Detailed Description:

Patients receive doxorubicin hydrochloride intravenously (IV) and vinblastine IV on day 1 of weeks 1, 3, 5, and 7; mechlorethamine hydrochloride IV on day 1 of weeks 1 and 5; vincristine sulfate IV and bleomycin IV on day 1 of weeks 2, 4, 6, and 8; etoposide IV on day 1 of weeks 3 and 7; and prednisone orally (PO) three times daily every other day for 8 weeks. Two to 3 weeks after all chemotherapy is given, patients not achieving a complete response undergo radiation therapy to individual nodal sites (tailored fields).

PRIMARY OBJECTIVES:

1. To increase the complete response rate of favorable risk patients (excluding all patients with stage IA nodular lymphocyte predominant Hodgkin lymphoma) after 8 weeks Stanford V by at least 20% compared to favorable risk patients on HOD 99 after 8 weeks vincristine, doxorubicin hydrochloride, methotrexate and prednisone (VAMP).

SECONDARY OBJECTIVES:

  1. To estimate the disease failure rate within the radiation fields.
  2. To examine patterns of treatment failure for children treated with low dose tailored field radiation therapy.
  3. To describe acute hematologic and infectious toxicities as they relate to transfusion requirements, growth factor support, episodes of febrile neutropenia, and hospitalizations, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
  4. To compare the survival distributions (event-free and overall) and cumulative incidence of local failure and toxicities of favorable risk patients treated with 8 weeks of Stanford V chemotherapy and low-dose tailored-field radiation to those on the favorable risk group of the HOD 99 study that received VAMP and low-dose involved-field radiation.
  5. To compare the survival distributions between patients that will not be prescribed radiotherapy after 8 weeks Stanford V and those patients on HOD 99 that did not receive radiotherapy after VAMP.
  6. To estimate the event-free survival distributions of favorable risk patients treated with Stanford V chemotherapy alone and patients treated with Stanford V chemotherapy plus low dose tailored field radiation.
  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed, previously untreated Hodgkin lymphoma.
  • Age: Participants must be 21 years of age or younger
  • Stage must be classified as one of the following:

Ann Arbor stage IA or IIA with:

  • Non-bulky mediastinal disease (< 33% mediastinal to thoracic ratio on CXR)
  • < 3 nodal regions involved on the same side of the diaphragm
  • No "E" lesion
  • Female patients who are post-menarchal must have a negative pregnancy test. Patients of reproductive potential must agree to use an effective contraceptive method.
  • Signed informed consent
  • If re-evaluation of a patient's disease shows intermediate risk features, the patient will be removed from the HOD08.

Exclusion Criteria:

  • Intermediate or High risk disease, defined as Stage IB, any III or IV or IA/IIA with "E" lesion(s), 3 or more nodal sites involved, or bulky mediastinal adenopathy
  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: NCT00846742

Contacts
Contact: Monika Metzger, MD, MSc 1-866-278-5833 info@stjude.org

Locations
United States, California
Packard Children's Hospital, Stanford University Recruiting
Palo Alto, California, United States, 94304
Contact: Michael Link, MD    650-495-8815    mlink@stanford.edu   
Principal Investigator: Michael Link, MD         
Rady Children's Hospital- San Diego Recruiting
San Diego, California, United States, 92123
Contact: Amy E Geddis, MD, PhD    858-966-5811    cmadigan@rchsd.org   
Principal Investigator: Amy E Geddis, MD, Ph.D         
United States, Maine
Maine Center for Cancer Medicine and Blood Disorders Recruiting
Scarborough, Maine, United States, 04074
Contact: Anne Rossi, MD    207-885-7565    rossia@mmc.org   
Principal Investigator: Anne Rossi, MD         
United States, Massachusetts
Dana-Farber Harvard Cancer Center Recruiting
Boston, Massachusetts, United States, 02115
Contact: Amy Billett, MD    617-632-5640    amy_billett@dfci.harvard.edu   
Principal Investigator: Amy Billett, MD         
Massachusetts General Hospital Cancer Center Recruiting
Boston, Massachusetts, United States, 02114
Contact: Alison Friedmann, MD    617-726-2737    afriedmann@partners.org   
Principal Investigator: Alison Friedmann, MD         
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Monika Metzger, MD, MSc    866-278-5833    info@stjude.org   
Principal Investigator: Monika Metzger, MD, MSc         
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: Monika Metzger, MD, MSc St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00846742     History of Changes
Other Study ID Numbers: HOD08
Study First Received: February 17, 2009
Last Updated: June 19, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by St. Jude Children's Research Hospital:
Hodgkin Lymphoma

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on October 19, 2014