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

Sponsor:	Children's Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00059839

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 Drug: vincristine sulfate	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
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:

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: 6-Mercaptopurine Prednisone Vincristine Methotrexate Doxorubicin Doxorubicin hydrochloride Myocet Vinblastine sulfate Vinblastine Vincristine sulfate Mercaptopurine

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Event-free survival [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Overall survival [ Designated as safety issue: No ]
Disease response [ Designated as safety issue: No ]

Estimated Enrollment:	200
Study Start Date:	November 2003
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I (consolidation therapy): Active Comparator In courses 1-3, patients receive doxorubicin IV over 15 minutes, vincristine 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, 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
Arm II (consolidation therapy): Experimental In 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. In courses 4 and 5, patients receive doxorubicin, prednisone, and mercaptopurine as in arm I and vinblastine as in arm II (courses 1-3). In 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. 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 Given IV

Arms

Assigned Interventions

Arm I (consolidation therapy): Active Comparator

In courses 1-3, patients receive doxorubicin IV over 15 minutes, vincristine 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, 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

Arm II (consolidation therapy): Experimental

In 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. In courses 4 and 5, patients receive doxorubicin, prednisone, and mercaptopurine as in arm I and vinblastine as in arm II (courses 1-3). In 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. 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

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.

Induction therapy: 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 CNS disease at diagnosis receive additional methotrexate IT on days 15, 29, and 36).

Patients then begin consolidation therapy on day 43.

Consolidation therapy: Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive course-specific regimens.
  - 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.
- Arm II: Patients receive course-specific regimens.
  - 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
- CD30+ disease
- 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)
AST or ALT less than 2.5 times ULN (unless due to lymphoma)

Renal

Not specified

Cardiovascular

Shortening fraction at least 27% by echocardiogram OR
Ejection fraction 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00059839

Show 159 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Jacqueline Kraveka, DO

Medical University of South Carolina

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Children's Oncology Group - Group Chair Office ( Gregory H. Reaman )
Study ID Numbers:	CDR0000298777, COG-ANHL0131
Study First Received:	May 6, 2003
Last Updated:	July 21, 2009
ClinicalTrials.gov Identifier:	NCT00059839 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

anaplastic large cell lymphoma

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Antimetabolites
Prednisone
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Vinblastine
Reproductive Control Agents
6-Mercaptopurine
Antibiotics, Antineoplastic
Hormones
Lymphoma, B-Cell

Lymphoma, T-Cell
Therapeutic Uses
Abortifacient Agents
Lymphoma, Large-Cell, Anaplastic
Methotrexate
Dermatologic Agents
Lymphoma
Nucleic Acid Synthesis Inhibitors
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Mitosis Modulators
Vincristine

ClinicalTrials.gov processed this record on November 09, 2009