Overview

This trial is active, not recruiting.

Condition leukemia
Treatments cyclophosphamide, cytarabine, daunorubicin hydrochloride, dexamethasone, leucovorin calcium, mercaptopurine, methotrexate, pegaspargase, thioguanine, vincristine sulfate
Phase phase 3
Sponsor Children's Oncology Group
Collaborator National Cancer Institute (NCI)
Start date April 2000
End date July 2005
Trial size 1076 participants
Trial identifier NCT00005596, 9905, CDR0000067704, COG-P9905, NCI-2012-02325, POG-9905

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 which regimen of chemotherapy is more effective for acute lymphoblastic leukemia.

PURPOSE: This randomized phase III trial is comparing four regimens of combination chemotherapy to see how well they work in treating children with newly diagnosed acute lymphoblastic leukemia.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients receive IT methotrexate on day 1 followed by methotrexate IV over 20 minutes followed by methotrexate continuously over 23.6 hrs on wks 7, 10, 13, 16,19, and 22. At 42 hrs after the beginning of the methotrexate infusion, patients receive oral leucovorin calcium every 6 hrs for a total of 3 doses. Patients also receive oral mercaptopurine daily beginning on wk 5 and continuing until the completion of consolidation therapy; oral dexamethasone twice daily on days 1-7 of wks 8 and 17; and vincristine sulfate IV on day 1 of wks 8, 9, 17, and 18.
dexamethasone DEX
6 mg/m2/day divided BID for 7 days during weeks 8 and 17.
leucovorin calcium
5 mg/m2/dose of leucovorin will be given PO q12h x 2 doses beginning 48 hours after the start of the MTX.
mercaptopurine 6-MP
50 mg/m2 dose po qhs Weeks 5 through 13 (total 9 wks) and from Week 24 until the end of consolidation. Only hold for uncomplicated myelosuppression, only if IV MTX course is delayed, until ANC > 500/μL and platelets > 75,000/uL
methotrexate MTX
IV: 1 gm/m2 given as a 200 mg/m2 bolus over 20 min followed by 800 mg/m2 over 23.6 hours given during Weeks 7, 10, 13, 16, 19, and 22. IT: Doses by age, Weeks 7, 10, 13, 16, 19 and 22.
vincristine sulfate VCR
1.5 mg/m2 IV on Day 1 of Weeks 8, 9, 17 and 18 (max 2 mg)
(Experimental)
Patients receive methotrexate IV over 4 hours on weeks 7, 10, 13, 16, 19, and 22. At 42 hours after the beginning of the methotrexate infusion, patients receive oral leucovorin calcium as in arm I. Patients also receive mercaptopurine, dexamethasone, vincristine sulfate, and IT methotrexate as in arm I.
dexamethasone DEX
6 mg/m2/day divided BID for 7 days during weeks 8 and 17.
leucovorin calcium
5 mg/m2/dose of leucovorin will be given PO q12h x 2 doses beginning 48 hours after the start of the MTX.
mercaptopurine 6-MP
50 mg/m2 dose po qhs Weeks 5 through 13 (total 9 wks) and from Week 24 until the end of consolidation. Only hold for uncomplicated myelosuppression, only if IV MTX course is delayed, until ANC > 500/μL and platelets > 75,000/uL
methotrexate MTX
IV: 1 gm/m2 given as a 200 mg/m2 bolus over 20 min followed by 800 mg/m2 over 23.6 hours given during Weeks 7, 10, 13, 16, 19, and 22. IT: Doses by age, Weeks 7, 10, 13, 16, 19 and 22.
vincristine sulfate VCR
1.5 mg/m2 IV on Day 1 of Weeks 8, 9, 17 and 18 (max 2 mg)
(Experimental)
Patients receive methotrexate IV as in arm I on weeks 7, 10, 13, 24, 27, and 30; leucovorin calcium as in arm I; pegaspargase IM on day 2, 3, OR 4 of wk 16; oral mercaptopurine daily on wks 5-13, and from wk 24 until the completion of consolidation therapy. Patients also receive IT methotrexate as in arm I on wks 7, 10, 13, 16, 20, 21, and 30; oral dexamethasone 2x daily on weeks 8, 16-18, and 28 for a total of 35 days; vincristine sulfate IV on day 1 of wks 8, 9, 16, 17, 18, 28, and 29; daunorubicin hydrochloride IV on day 1 of wks 16-18; cyclophosphamide IV over 30 minutes on day 1 of week 20; cytarabine IV or subcutaneously daily on days 2-5 of wks 20 and 21; and oral thioguanine daily on wks 20-21.
cyclophosphamide
cytarabine
daunorubicin hydrochloride daunomycin
30 mg/m2 IV Day 1 of weeks 16, 17, and 18. Give Week 16 dose if ANC ≥ 500/μL and platelets ≥ 75,000/μL. Continue to give during Weeks 17 and 18, even in the face of uncomplicated myelosuppression
dexamethasone DEX
6 mg/m2/day divided BID for 7 days during weeks 8 and 17.
leucovorin calcium
5 mg/m2/dose of leucovorin will be given PO q12h x 2 doses beginning 48 hours after the start of the MTX.
mercaptopurine 6-MP
50 mg/m2 dose po qhs Weeks 5 through 13 (total 9 wks) and from Week 24 until the end of consolidation. Only hold for uncomplicated myelosuppression, only if IV MTX course is delayed, until ANC > 500/μL and platelets > 75,000/uL
methotrexate MTX
IV: 1 gm/m2 given as a 200 mg/m2 bolus over 20 min followed by 800 mg/m2 over 23.6 hours given during Weeks 7, 10, 13, 16, 19, and 22. IT: Doses by age, Weeks 7, 10, 13, 16, 19 and 22.
pegaspargase PEG
2,500 IU/m2 will be given IM x 1 on Days 2,3,or 4 of Week 16; > or = 1 day after the IT MTX
thioguanine 6-TG
60 mg/m2 po qhs during Weeks 20 and 21 (total 14 days). Start week 20 when ANC > or = 500/ul and platelets > or = 75,000/uL. Continue to give all 14 doses despite uncomplicated myelosuppression.
vincristine sulfate VCR
1.5 mg/m2 IV on Day 1 of Weeks 8, 9, 17 and 18 (max 2 mg)
(Experimental)
Patients receive methotrexate IV as in arm II on weeks 7, 10, 13, 24, 27, and 30; leucovorin calcium as in arm I; and pegaspargase, mercaptopurine, IT methotrexate, dexamethasone, vincristine sulfate, daunorubicin hydrochloride, cyclophosphamide, cytarabine, and thioguanine as in arm III.
cyclophosphamide
cytarabine
daunorubicin hydrochloride daunomycin
30 mg/m2 IV Day 1 of weeks 16, 17, and 18. Give Week 16 dose if ANC ≥ 500/μL and platelets ≥ 75,000/μL. Continue to give during Weeks 17 and 18, even in the face of uncomplicated myelosuppression
dexamethasone DEX
6 mg/m2/day divided BID for 7 days during weeks 8 and 17.
leucovorin calcium
5 mg/m2/dose of leucovorin will be given PO q12h x 2 doses beginning 48 hours after the start of the MTX.
mercaptopurine 6-MP
50 mg/m2 dose po qhs Weeks 5 through 13 (total 9 wks) and from Week 24 until the end of consolidation. Only hold for uncomplicated myelosuppression, only if IV MTX course is delayed, until ANC > 500/μL and platelets > 75,000/uL
methotrexate MTX
IV: 1 gm/m2 given as a 200 mg/m2 bolus over 20 min followed by 800 mg/m2 over 23.6 hours given during Weeks 7, 10, 13, 16, 19, and 22. IT: Doses by age, Weeks 7, 10, 13, 16, 19 and 22.
pegaspargase PEG
2,500 IU/m2 will be given IM x 1 on Days 2,3,or 4 of Week 16; > or = 1 day after the IT MTX
thioguanine 6-TG
60 mg/m2 po qhs during Weeks 20 and 21 (total 14 days). Start week 20 when ANC > or = 500/ul and platelets > or = 75,000/uL. Continue to give all 14 doses despite uncomplicated myelosuppression.
vincristine sulfate VCR
1.5 mg/m2 IV on Day 1 of Weeks 8, 9, 17 and 18 (max 2 mg)

Primary Outcomes

Measure
Improvement in outcome in children receiving multidrug delayed-intensification therapy
time frame: Up to 4 years

Secondary Outcomes

Measure
Event-free survival, minimal residual disease, and early response
time frame: 5 years
Occurrence of anticipated failures
time frame: Up to 5 years
Total grade 3+ central nervous system (CNS) toxicity rates based on the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
time frame: Up to 5 years

Eligibility Criteria

Male or female participants from 1 year up to 21 years old.

DISEASE CHARACTERISTICS: - Confirmed diagnosis of newly diagnosed B-precursor acute lymphocytic leukemia - Standard risk (not low, high, or very high risk) - Prior registration and treatment on POG 9900 Classification Study PATIENT CHARACTERISTICS: Age: - 1 to 21 at diagnosis Performance status: - Not specified Life expectancy: - Not specified Hematopoietic: - Not specified Hepatic: - Not specified Renal: - Not specified Other: - Not pregnant or nursing - Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy - Not specified Chemotherapy - Not specified Endocrine therapy - Not specified Radiotherapy - Not specified Surgery - Not specified

Additional Information

Official title ALinC 17: Protocol for Patients With Newly Diagnosed Standard Risk Acute Lymphoblastic Leukemia (ALL): A Phase III Study
Description OBJECTIVES: - Determine if multidrug delayed-intensification therapy improves outcome in children with newly diagnosed standard-risk acute lymphocytic leukemia. - Compare the efficacy and toxicity of methotrexate administered over 4 hours vs methotrexate administered over 24 hours in this patient population. - Determine the correlation between event-free survival, minimal residual disease, and early response in this patient population treated with this multiple drug regimen. OUTLINE: This is a randomized, multicenter study. - Induction (weeks 1-4): Patients receive induction therapy on POG 9900. - Consolidation (weeks 5-32): Patients are randomized to one of four treatment arms. Patients with t(1;19) are randomized to either arm III or arm IV. - Arm I (weeks 5-24): Patients receive IT methotrexate (MTX) on day 1 followed by MTX IV over 20 minutes followed by MTX continuously over 23.6 hours on weeks 7, 10, 13, 16,19, and 22. At 42 hours after the beginning of the MTX infusion, patients receive oral leucovorin calcium every 6 hours for a total of 3 doses. Patients also receive oral mercaptopurine daily beginning on week 5 and continuing until the completion of consolidation therapy; oral dexamethasone twice daily on days 1-7 of weeks 8 and 17; and vincristine IV on day 1 of weeks 8, 9, 17, and 18. - Arm II (weeks 5-24): Patients receive MTX IV over 4 hours on weeks 7, 10, 13, 16, 19, and 22. At 42 hours after the beginning of the MTX infusion, patients receive oral leucovorin calcium as in arm I. Patients also receive mercaptopurine, dexamethasone, vincristine, and IT MTX as in arm I. - Arm III (weeks 5-32): Patients receive MTX IV as in arm I on weeks 7, 10, 13, 24, 27, and 30; leucovorin calcium as in arm I; pegaspargase IM on day 2, 3, OR 4 of week 16; and oral mercaptopurine daily on weeks 5-13, and from week 24 until the completion of consolidation therapy. Patients also receive IT MTX as in arm I on weeks 7, 10, 13, 16, 20, 21, and 30; oral dexamethasone twice daily on weeks 8, 16-18, and 28 for a total of 35 days; vincristine IV on day 1 of weeks 8, 9, 16, 17, 18, 28, and 29; daunorubicin IV on day 1 of weeks 16-18; cyclophosphamide IV over 30 minutes on day 1 of week 20; cytarabine IV or subcutaneously daily on days 2-5 of weeks 20 and 21; and oral thioguanine daily on weeks 20-21. - Arm IV (weeks 5-32): Patients receive MTX IV as in arm II on weeks 7, 10, 13, 24, 27, and 30; leucovorin calcium as in arm I; and pegaspargase, mercaptopurine, IT MTX, dexamethasone, vincristine, daunorubicin, cyclophosphamide, cytarabine, and thioguanine as in arm III. - Intensive continuation (weeks 25-80): At weeks 25-72 for arms I and II, and at weeks 33-80 for arms III and IV, patients receive oral MTX every 6 hours for 4 doses on weeks 1, 3, 5, 7, 9, and 11; oral mercaptopurine daily; oral leucovorin calcium every 12 hours for 2 doses beginning 48 hours after the start of MTX; IT MTX and vincristine IV on day 1 of week 12; and oral dexamethasone twice daily on days 1-7, beginning with the administration of vincristine. Treatment repeats every 12 weeks for 4 courses. - Additional continuation (weeks 73-130): At weeks 73-130 for arms I and II, and at weeks 81-130 for arms III and IV, patients receive oral MTX weekly; oral mercaptopurine daily; vincristine IV on day 1 every 12 weeks; oral dexamethasone as during intensive continuation therapy; and IT MTX on day 1 every 12 weeks, beginning with the last week of the first course (in place of oral MTX). Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, every 6 months for 1 year, and then every 6-12 months for 1 year. PROJECTED ACCRUAL: A total of 1,014 patients will be accrued for this study within 3.22 years.
Trial information was received from ClinicalTrials.gov and was last updated in May 2015.
Information provided to ClinicalTrials.gov by Children's Oncology Group.