Brief Summary
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.
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.
Brief Title
Comparison of Two Combination Chemotherapy Regimens With Either Vincristine or Vinblastine in Treating Patients With Advanced Anaplastic Large Cell Lymphoma
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.
* 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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Lymphoma
Eligibility 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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
Keywords
anaplastic large cell lymphoma
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Maximum Age
20 Years
NCT Id
NCT00059839
Org Class
Network
Org Full Name
Children's Oncology Group
Org Study Id
ANHL0131
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
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. To measure Event Free Survival, repeated one-sided logrank tests will be performed The upper critical values are based on the one-sided alpha-spending functions of t2 (alpha=0.05) and the lower critical values are based on testing the alternative hypothesis at 0.005 level.
Outcome Measure
Event-free Survival (EFS)
Outcome Time Frame
From first enrollment up to 3 years.
Secondary Ids
Secondary Id
CDR0000298777
Secondary Id
COG-ANHL0131
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Maximum Age Number (converted to Years and rounded down)
20
Minimum Age Number (converted to Years and rounded down)
0
Investigators
Investigator Type
Principal Investigator
Investigator Name
Jonathan Gill
Investigator Email
jgill@montefiore.org
Investigator Phone
718-741-2331