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

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

MedlinePlus related topics:

Cancer Lymphoma

Drug Information available for:

Doxorubicin Doxorubicin hydrochloride Mercaptopurine 6-Mercaptopurine Methotrexate Prednisone Vincristine sulfate Vincristine Vinblastine Vinblastine sulfate

U.S. FDA Resources

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

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

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 163 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

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

Study ID Numbers:	CDR0000298777, COG-ANHL0131
First Received:	May 6, 2003
Last Updated:	November 25, 2008
ClinicalTrials.gov Identifier:	NCT00059839
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

anaplastic large cell lymphoma

Study placed in the following topic categories:

Prednisone

Lymphoma, Large B-Cell, Diffuse

Immunoproliferative Disorders

Vincristine

Vinblastine

6-Mercaptopurine

Doxorubicin

Folic Acid

Lymphoma, B-Cell

Lymphoma, large-cell

Lymphatic Diseases

Lymphoma, T-Cell

B-cell lymphomas

Lymphoma, Large-Cell, Anaplastic

Methotrexate

Anaplastic large cell lymphoma

Lymphoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphoma

Additional relevant MeSH terms:

Anti-Inflammatory Agents

Antimetabolites

Antimetabolites, Antineoplastic

Immunologic Factors

Molecular Mechanisms of Pharmacological Action

Antineoplastic Agents

Physiological Effects of Drugs

Hormones, Hormone Substitutes, and Hormone Antagonists

Reproductive Control Agents

Antibiotics, Antineoplastic

Hormones

Therapeutic Uses

Abortifacient Agents

Dermatologic Agents

Nucleic Acid Synthesis Inhibitors

Neoplasms by Histologic Type

Immune System Diseases

Antineoplastic Agents, Hormonal

Mitosis Modulators

Enzyme Inhibitors

Antimitotic Agents

Abortifacient Agents, Nonsteroidal

Folic Acid Antagonists

Immunosuppressive Agents

Glucocorticoids

Pharmacologic Actions

Neoplasms

Tubulin Modulators

Antirheumatic Agents

Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on November 30, 2008

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