Comparison of Two Combination Chemotherapy Regimens With Either Vincristine or Vinblastine in Treating Patients With Advanced Anaplastic Large Cell Lymphoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00059839
First received: May 6, 2003
Last updated: July 25, 2013
Last verified: July 2013
  Purpose

RATIONALE: Drugs used in chemotherapy 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. It is not yet known if combination chemotherapy with vinblastine is more effective than combination chemotherapy with vincristine in treating advanced anaplastic large cell lymphoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of two combination chemotherapy regimens with either vinblastine or vincristine in treating patients who have newly diagnosed advanced anaplastic large cell lymphoma.


Condition Intervention Phase
Lymphoma
Drug: doxorubicin hydrochloride
Drug: mercaptopurine
Drug: methotrexate
Drug: prednisone
Drug: vinblastine sulfate
Drug: vincristine sulfate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Trial of Treatment of Advanced-Stage Anaplastic Large Cell Lymphoma (ALCL) With Standard APO (Doxorubicin, Prednisone, Vincristine) Versus Consolidation With a Regimen Including Vinblastine

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Event-free Survival (EFS) [ Time Frame: From first enrollment up to 3 years. ] [ Designated as safety issue: No ]
    Percentage of EFS patients. This is measured as the time from study entry until disease progression, disease recurrence, occurrence of a second malignant neoplasm, or death from any cause.


Enrollment: 129
Study Start Date: November 2003
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Standard APO with Vincristine (Arm I )
In courses 1-3, patients receive doxorubicin hydrochloride IV over 15 minutes, vincristine sulfate IV, and methotrexate intrathecally (IT) on day 1 and oral prednisone three times daily and oral mercaptopurine once daily on days 1-5. In courses 4 and 5, patients receive doxorubicin, vincristine sulfate, prednisone, and mercaptopurine as in courses 1-3. In courses 6-15, patients receive vincristine, prednisone, and mercaptopurine as in courses 1-3 and methotrexate IV on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.
Drug: doxorubicin hydrochloride
Given IV
Drug: mercaptopurine
Given by mouth
Drug: methotrexate
Given IV and intrathecally
Drug: prednisone
Given by mouth
Drug: vincristine sulfate
Given IV
Experimental: Consolidation with Vinblastine
In courses 1-3, patients receive doxorubicin hydrochloride, methotrexate IT, prednisone, and mercaptopurine as in arm I and vinblastine sulfate IV over 1 minute on days 1, 8, and 15. In courses 4 and 5, patients receive doxorubicin, prednisone, and mercaptopurine as in arm I and vinblastine sulfate as in arm II (courses 1-3). In courses 6-15, patients receive prednisone and mercaptopurine as in arm I, vinblastine sulfate as in arm II (courses 1-3), and methotrexate IV on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.
Drug: doxorubicin hydrochloride
Given IV
Drug: mercaptopurine
Given by mouth
Drug: methotrexate
Given IV and intrathecally
Drug: prednisone
Given by mouth
Drug: vinblastine sulfate
Given IV

Detailed Description:

OBJECTIVES:

  • Compare the efficacy of a consolidation chemotherapy regimen comprising doxorubicin and prednisone in combination with vincristine vs vinblastine, in terms of event-free survival, in patients with advanced anaplastic large cell lymphoma.
  • Compare overall survival of patients treated with these regimens.
  • Compare the toxic effects of these regimens in these patients.
  • Correlate biological tumor characteristics and outcome in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study.

Patients are randomized at enrollment to receive either Standard APO regimen or a consolidation regimen including vinblastine (VBL).

  • Induction therapy: All Patients receive doxorubicin IV over 15 minutes on days 1 and 22; vincristine IV on days 1, 8, 15, 22, and 29; oral prednisone 3 times daily on days 1-28; and intrathecal (IT) methotrexate on days 1, 8, and 22 (patients with central nervous system (CNS) disease at diagnosis receive additional methotrexate IT on days 15, 29, and 36).

Patients undergo restaging after Induction such that consolidation therapy is started on day 43. All patients with complete response (CR), complete response unconfirmed (CRu) or partial response (PR) proceed to Consolidation based on CT or MRI scans at the end of induction (week 6). All other patients will be removed from protocol therapy and will be followed until they meet the criteria for off study. Follow-up data will be required unless consent is withdrawn.

  • Standard APO (Arm I): Patients receive course-specific regimens without vinblastine.

    • Courses 1-3: Patients receive doxorubicin IV over 15 minutes, vincristine IV, and methotrexate IT on day 1 and oral prednisone three times daily and oral mercaptopurine once daily on days 1-5.
    • Courses 4-5: Patients receive doxorubicin, vincristine, prednisone, and mercaptopurine as in courses 1-3.
    • Courses 6-15: Patients receive vincristine, prednisone, and mercaptopurine as in courses 1-3 and methotrexate IV on day 1.
  • Consolidation with vinblastine (Arm II): Patients receive course-specific regimens including vinblastine.

    • Courses 1-3: Patients receive doxorubicin, methotrexate IT, prednisone, and mercaptopurine as in arm I and vinblastine IV over 1 minute on days 1, 8, and 15.
    • Courses 4-5: Patients receive doxorubicin, prednisone, and mercaptopurine as in arm I and vinblastine as in arm II (courses 1-3).
    • Courses 6-15: Patients receive prednisone and mercaptopurine as in arm I, vinblastine as in arm II (courses 1-3), and methotrexate IV on day 1.

In both arms and all courses, treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed monthly for 1 year, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 200-250 patients (100-125 per treatment arm) will be accrued for this study within 5 years.

  Eligibility

Ages Eligible for Study:   up to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Newly diagnosed advanced anaplastic large cell lymphoma

    • Cluster of differentiation antigen 30 (CD30+)
    • Murphy stage III or IV
  • No B-cell large cell lymphoma
  • No disease limited to the skin (regardless of how wide-spread)

PATIENT CHARACTERISTICS:

Age

  • Under 21

Performance status

  • Not specified

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) or alanine transaminase (ALT) less than 2.5 times ULN (unless due to lymphoma)

Renal

  • Not specified

Cardiovascular

  • Shortening fraction (SF) at least 27% by echocardiogram OR
  • Ejection fraction (EF) at least 50% by radionuclide angiogram

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • Not specified

Endocrine therapy

  • Prior steroids for management of a mediastinal mass allowed

Radiotherapy

  • Prior limited-dose radiotherapy for a mediastinal mass allowed

Surgery

  • Not specified
  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: NCT00059839

  Show 159 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Jacqueline Kraveka, DO Medical University of South Carolina
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00059839     History of Changes
Other Study ID Numbers: ANHL0131, CDR0000298777, COG-ANHL0131
Study First Received: May 6, 2003
Results First Received: June 28, 2013
Last Updated: July 25, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Oncology Group:
anaplastic large cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Large-Cell, Anaplastic
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, T-Cell
6-Mercaptopurine
Methotrexate
Liposomal doxorubicin
Doxorubicin
Prednisone
Vinblastine
Vincristine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors

ClinicalTrials.gov processed this record on August 27, 2014