Trial Outcomes & Findings for Comparison of Two Combination Chemotherapy Regimens With Either Vincristine or Vinblastine in Treating Patients With Advanced Anaplastic Large Cell Lymphoma (NCT NCT00059839)

Last Updated: 2014-09-22

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

129 participants

Primary outcome timeframe

From first enrollment up to 3 years.

Results posted on

2014-09-22

Participant Flow

This is a multi-center, phase III, randomized trial for newly diagnosed children with advanced-stage anaplastic large cell lymphoma (ALCL). The study was activated on November 3, 2003 and the first date of enrollment was January 13, 2004.

Randomization occurs at the time of enrollment with all participants receiving Standard Induction of Doxorubicin, Prednisone and Vincristine (APO) and are evaluated at week 6 for continuation therapy.

Participant milestones

Participant milestones
Measure	Standard (APO) With Vincristine (Arm I) In courses 1-3, patients receive doxorubicin hydrochloride (30 mg/m2) IV over 15 minutes, vincristine sulfate (1.5 mg/m2 (maximum dose 2 mg)) IV, and methotrexate intrathecally (age-adjusted dosing) (IT) on day 1 and oral prednisone (40 mg/m2/day) three times daily and oral mercaptopurine (225 mg/m2) once daily on days 1-5. In courses 4 and 5, patients receive doxorubicin (30 mg/m2), vincristine sulfate (1.5 mg/m2 (Maximum dose 2 mg)), prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in courses 1-3. In courses 6-15, patients receive vincristine sulfate (1.5 mg/m2), prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in courses 1-3 and methotrexate (60 mg/m2) IV on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.	Consolidation (Includes Vinblastine) (Arm II) In courses 1-3, patients receive doxorubicin hydrochloride (30 mg/m2) IV, methotrexate (age adjusted dosing) IT, prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in arm I and vinblastine sulfate (4 mg/m2) IV over 1 minute on days 1, 8, and 15. In courses 4 and 5, patients receive doxorubicin hydrochloride (30 mg/m2) IV, prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in arm I and vinblastine sulfate (4 mg/m2) as in arm II (courses 1-3). In courses 6-15, patients receive prednisone (120 mg/m2/day) and mercaptopurine (225 mg/m2) as in arm I, vinblastine sulfate (4 mg/m2) IV as in arm II (courses 1-3), and methotrexate (60 mg/m2) IV on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	65	64
Overall Study COMPLETED	53	47
Overall Study NOT COMPLETED	12	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Standard (APO) With Vincristine (Arm I) In courses 1-3, patients receive doxorubicin hydrochloride (30 mg/m2) IV over 15 minutes, vincristine sulfate (1.5 mg/m2 (maximum dose 2 mg)) IV, and methotrexate intrathecally (age-adjusted dosing) (IT) on day 1 and oral prednisone (40 mg/m2/day) three times daily and oral mercaptopurine (225 mg/m2) once daily on days 1-5. In courses 4 and 5, patients receive doxorubicin (30 mg/m2), vincristine sulfate (1.5 mg/m2 (Maximum dose 2 mg)), prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in courses 1-3. In courses 6-15, patients receive vincristine sulfate (1.5 mg/m2), prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in courses 1-3 and methotrexate (60 mg/m2) IV on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.	Consolidation (Includes Vinblastine) (Arm II) In courses 1-3, patients receive doxorubicin hydrochloride (30 mg/m2) IV, methotrexate (age adjusted dosing) IT, prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in arm I and vinblastine sulfate (4 mg/m2) IV over 1 minute on days 1, 8, and 15. In courses 4 and 5, patients receive doxorubicin hydrochloride (30 mg/m2) IV, prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in arm I and vinblastine sulfate (4 mg/m2) as in arm II (courses 1-3). In courses 6-15, patients receive prednisone (120 mg/m2/day) and mercaptopurine (225 mg/m2) as in arm I, vinblastine sulfate (4 mg/m2) IV as in arm II (courses 1-3), and methotrexate (60 mg/m2) IV on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.
Overall Study Death	1	1
Overall Study Lack of Efficacy	6	5
Overall Study Lost to Follow-up	2	0
Overall Study Physician Decision	1	2
Overall Study Withdrawal by Subject	1	6
Overall Study Ineligible	1	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Standard (APO) With Vincristine (Arm I) n=65 Participants In courses 1-3, patients receive doxorubicin hydrochloride (30 mg/m2) IV over 15 minutes, vincristine sulfate (1.5 mg/m2 (maximum dose 2 mg)) IV, and methotrexate intrathecally (age-adjusted dosing) (IT) on day 1 and oral prednisone (40 mg/m2/day) three times daily and oral mercaptopurine (225 mg/m2) once daily on days 1-5. In courses 4 and 5, patients receive doxorubicin (30 mg/m2), vincristine sulfate (1.5 mg/m2 (Maximum dose 2 mg)), prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in courses 1-3. In courses 6-15, patients receive vincristine sulfate (1.5 mg/m2), prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in courses 1-3 and methotrexate (60 mg/m2) IV on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.	Consolidation (Includes Vinblastine) (Arm II) n=64 Participants In courses 1-3, patients receive doxorubicin hydrochloride (30 mg/m2) IV, methotrexate (age adjusted dosing) IT, prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in arm I and vinblastine sulfate (4 mg/m2) IV over 1 minute on days 1, 8, and 15. In courses 4 and 5, patients receive doxorubicin hydrochloride (30 mg/m2) IV, prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in arm I and vinblastine sulfate (4 mg/m2) as in arm II (courses 1-3). In courses 6-15, patients receive prednisone (120 mg/m2/day) and mercaptopurine (225 mg/m2) as in arm I, vinblastine sulfate (4 mg/m2) IV as in arm II (courses 1-3), and methotrexate (60 mg/m2) IV on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.	Total n=129 Participants Total of all reporting groups
Age, Categorical <=18 years	62 Participants n=93 Participants	62 Participants n=4 Participants	124 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=93 Participants	2 Participants n=4 Participants	5 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Sex: Female, Male Female	24 Participants n=93 Participants	27 Participants n=4 Participants	51 Participants n=27 Participants
Sex: Female, Male Male	41 Participants n=93 Participants	37 Participants n=4 Participants	78 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=93 Participants	8 Participants n=4 Participants	18 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	52 Participants n=93 Participants	55 Participants n=4 Participants	107 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=93 Participants	1 Participants n=4 Participants	4 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	5 Participants n=93 Participants	3 Participants n=4 Participants	8 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	7 Participants n=93 Participants	12 Participants n=4 Participants	19 Participants n=27 Participants
Race (NIH/OMB) White	47 Participants n=93 Participants	42 Participants n=4 Participants	89 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=93 Participants	7 Participants n=4 Participants	13 Participants n=27 Participants
Region of Enrollment United States	59 participants n=93 Participants	52 participants n=4 Participants	111 participants n=27 Participants
Region of Enrollment Canada	3 participants n=93 Participants	9 participants n=4 Participants	12 participants n=27 Participants
Region of Enrollment Australia	2 participants n=93 Participants	2 participants n=4 Participants	4 participants n=27 Participants
Region of Enrollment Switzerland	1 participants n=93 Participants	1 participants n=4 Participants	2 participants n=27 Participants

PRIMARY outcome

Timeframe: From first enrollment up to 3 years.

Population: 64 patients from Arm I were analyzed for this outcome measure, one patient was deemed ineligible. 61 patients from Arm II were analyzed for this outcome measure, three patients were deemed ineligible.

Outcome measures

Outcome measures
Measure	Standard (APO) With Vincristine (Arm I) n=64 Participants In courses 1-3, patients receive doxorubicin hydrochloride (30 mg/m2) IV over 15 minutes, vincristine sulfate (1.5 mg/m2 (maximum dose 2 mg)) IV, and methotrexate intrathecally (age-adjusted dosing) (IT) on day 1 and oral prednisone (40 mg/m2/day) three times daily and oral mercaptopurine (225 mg/m2) once daily on days 1-5. In courses 4 and 5, patients receive doxorubicin (30 mg/m2), vincristine sulfate (1.5 mg/m2 (Maximum dose 2 mg)), prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in courses 1-3. In courses 6-15, patients receive vincristine sulfate (1.5 mg/m2), prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in courses 1-3 and methotrexate (60 mg/m2) IV on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.	Consolidation (Includes Vinblastine) (Arm II) n=61 Participants In courses 1-3, patients receive doxorubicin hydrochloride (30 mg/m2) IV, methotrexate (age adjusted dosing) IT, prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in arm I and vinblastine sulfate (4 mg/m2) IV over 1 minute on days 1, 8, and 15. In courses 4 and 5, patients receive doxorubicin hydrochloride (30 mg/m2) IV, prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in arm I and vinblastine sulfate (4 mg/m2) as in arm II (courses 1-3). In courses 6-15, patients receive prednisone (120 mg/m2/day) and mercaptopurine (225 mg/m2) as in arm I, vinblastine sulfate (4 mg/m2) IV as in arm II (courses 1-3), and methotrexate (60 mg/m2) IV on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.
Event-free Survival (EFS)	74 percentage of participants Interval 61.0 to 84.0	79 percentage of participants Interval 65.0 to 87.0

Adverse Events

Standard (APO) With Vincristine (Arm I)

Serious events: 2 serious events

Other events: 47 other events

Deaths: 0 deaths

Consolidation (Includes Vinblastine) (Arm II)

Serious events: 4 serious events

Other events: 52 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Results Reporting Coordinator

Children's Oncology Group

Phone: 626-447-0064

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Standard (APO) With Vincristine (Arm I) n=64 participants at risk In courses 1-3, patients receive doxorubicin hydrochloride (30 mg/m2) IV over 15 minutes, vincristine sulfate (1.5 mg/m2 (maximum dose 2 mg)) IV, and methotrexate intrathecally (age-adjusted dosing) (IT) on day 1 and oral prednisone (40 mg/m2/day) three times daily and oral mercaptopurine (225 mg/m2) once daily on days 1-5. In courses 4 and 5, patients receive doxorubicin (30 mg/m2), vincristine sulfate (1.5 mg/m2 (Maximum dose 2 mg)), prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in courses 1-3. In courses 6-15, patients receive vincristine sulfate (1.5 mg/m2), prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in courses 1-3 and methotrexate (60 mg/m2) IV on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.	Consolidation (Includes Vinblastine) (Arm II) n=61 participants at risk In courses 1-3, patients receive doxorubicin hydrochloride (30 mg/m2) IV, methotrexate (age adjusted dosing) IT, prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in arm I and vinblastine sulfate (4 mg/m2) IV over 1 minute on days 1, 8, and 15. In courses 4 and 5, patients receive doxorubicin hydrochloride (30 mg/m2) IV, prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in arm I and vinblastine sulfate (4 mg/m2) as in arm II (courses 1-3). In courses 6-15, patients receive prednisone (120 mg/m2/day) and mercaptopurine (225 mg/m2) as in arm I, vinblastine sulfate (4 mg/m2) IV as in arm II (courses 1-3), and methotrexate (60 mg/m2) IV on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	0.00% 0/64 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.	1.6% 1/61 • Number of events 1 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.
Blood and lymphatic system disorders "Blood and lymphatic system disorders - Other"	0.00% 0/64 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.	1.6% 1/61 • Number of events 1 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.
Blood and lymphatic system disorders Disseminated intravascular coagulation	1.6% 1/64 • Number of events 1 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.	0.00% 0/61 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/64 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.	1.6% 1/61 • Number of events 1 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.
Cardiac disorders Cardiac arrest	1.6% 1/64 • Number of events 1 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.	0.00% 0/61 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.
Cardiac disorders "Cardiac disorders - Other"	1.6% 1/64 • Number of events 1 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.	1.6% 1/61 • Number of events 1 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.
Gastrointestinal disorders Vomiting	0.00% 0/64 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.	1.6% 1/61 • Number of events 1 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.
General disorders Death NOS	0.00% 0/64 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.	1.6% 1/61 • Number of events 1 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.
Hepatobiliary disorders Hepatic failure	1.6% 1/64 • Number of events 1 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.	100.0% 1/1 • Number of events 1 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.
Investigations Activated partial thromboplastin time prolonged	1.6% 1/64 • Number of events 1 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.	1.6% 1/61 • Number of events 1 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.
Investigations Aspartate aminotransferase increased	1.6% 1/64 • Number of events 1 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.	1.6% 1/61 • Number of events 1 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.
Investigations CPK increased	1.6% 1/64 • Number of events 1 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.	0.00% 0/61 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/64 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.	1.6% 1/61 • Number of events 1 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.
Nervous system disorders "Nervous system disorders - Other"	0.00% 0/64 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.	1.6% 1/61 • Number of events 1 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.
Nervous system disorders Seizure	1.6% 1/64 • Number of events 1 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.	1.6% 1/61 • Number of events 1 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.00% 0/64 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.	1.6% 1/61 • Number of events 1 64 patients are included for Arm I adverse events as one patient was deemed ineligible. 61 patients are included for Arm II adverse events as three patients were deemed ineligible.