Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Induction Intensification in Treating Infants With Newly Diagnosed Acute Lymphoblastic Leukemia

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Completed Under 1 at diagnosis NCI COG-P9407 POG-9407, P9407, NCT00002756

Objectives

Primary

1. Assess the feasibility of intensification with two courses of high-dose methotrexate followed by one course of cyclophosphamide/etoposide during induction and later as consolidation in infants with newly diagnosed acute lymphoblastic leukemia.
2. Determine event-free survival after shortened, intensive therapy in these patients.
3. Compare event-free survival rates of infants receiving this regimen whose leukemic blasts have or do not have translocations involving the 11q23 gene MLL.

Secondary

1. Correlate the presence of minimal residual disease at completion of induction, beginning of continuation, and at completion of therapy with patient outcome.
2. Investigate the clinical prognostic features that may be associated with outcome in infants, such as bone marrow blast content at day 8, white blood cell count, and age.
3. Correlate biologic characteristics of the leukemia cells at diagnosis (protocol POG-9900) with outcome in patients treated with this regimen.
4. Characterize patterns of gene expression associated with host and disease characteristics and treatment response in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Newly diagnosed acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia
  • No infants less than 36 weeks' gestation
  • CNS or testicular disease permitted



• No B-cell ALL or acute myeloid leukemia



• Previously untreated except for the following:
  • Steroid treatment within 48 hours of diagnosis allowed with physical examination and differential CBC immediately prior to beginning steroids



• Concurrent registration on protocol POG-9900 (ALL classification study) required



• Patients registered on POG-9407 are eligible for the pharmacokinetic part of the study

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• See Disease Characteristics
• No concurrent chronic steroid treatment

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• No other concurrent anticancer therapy

Patient Characteristics:

Age:

• Under 1 at diagnosis

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• No uncontrolled infection
• Adequate major organ function

Expected Enrollment

Approximately 58-104 patients will be accrued for this study within 2.1 years.

Outcomes

Feasibility of intensification
Event-free survival
Comparison of event-free survival rates in infants with and without leukemic blasts translocations

Correlation of minimal residual disease at completion of induction, beginning of continuation, and at completion of therapy with patient outcome
Clinical prognostic features associated with outcome
Correlation of biologic characteristics of leukemia cells at diagnosis with outcome
Patterns of gene expression

Outline

This is a multicenter study. Patients are stratified according to participating center and presence of CNS disease (yes vs no).

Patients receive induction chemotherapy comprising vincristine IV on days 1, 8, and 15; oral prednisone three times a day on days 1-21; daunorubicin IV over 30 minutes on days 1-2; cyclophosphamide IV over 30 minutes every 12 hours on days 3-4; and asparaginase intramuscularly (IM) on days 4, 6, 8, 10, 12, 15, 17, and 19. Patients also receive triple intrathecal therapy comprising methotrexate, hydrocortisone, and cytarabine on days 1, 8, and 15 and filgrastim (G-CSF) subcutaneously (SC) or IV beginning on day 5 and continuing until day 20, regardless of blood counts.

Patients receive induction intensification chemotherapy comprising high-dose methotrexate IV over 24 hours; triple intrathecal therapy as per induction therapy on days 22 and 29; and leucovorin calcium IV every 6 hours for 2 doses beginning 42 hours after start of high-dose methotrexate and then orally every 6 hours for 3 doses. Patients also receive etoposide IV over 2 hours and cyclophosphamide IV over 30 minutes on days 36-40. Patients receive G-CSF SC or IV beginning on day 41 and continuing until blood counts recover.

Patients achieving morphologic remission and recovery of blood counts while off G-CSF for 48 hours receive reinduction chemotherapy comprising the same regimen as in induction therapy with the exception of asparaginase IM beginning on day 1 (week 8) and continuing every Monday, Wednesday, and Friday for a total of 8 doses and triple intrathecal therapy on days 1 and 15 only (weeks 8 and 10). Patients receive G-CSF SC or IV beginning on day 5 and continuing until blood counts recover.

After blood count recovery, patients receive consolidation chemotherapy comprising triple intrathecal therapy as per induction therapy on day 1 (week 11); high-dose methotrexate IV over 24 hours on weeks 8 and 12; and leucovorin calcium IV every 6 hours for 2 doses beginning 42 hours after start of high-dose methotrexate and then orally every 6 hours for 3 doses. Patients also receive etoposide IV over 2 hours followed by cyclophosphamide IV over 30 minutes on days 15-19 (week 13). Patients receive G-CSF SC or IV beginning on day 20 and continuing until blood counts recover. On days 29-31 (week 15), patients receive high-dose cytarabine IV over 3 hours every 12 hours for 4 doses and asparaginase IM 6 hours after completion of high-dose cytarabine. Patients receive G-CSF beginning 24 hours after completion of asparaginase and continuing until blood counts recover.

Patients achieving morphologic remission and blood count recovery while off G-CSF for 48 hours receive continuation therapy comprising vincristine IV on day 1; oral prednisone three times a day on days 1-5; and triple intrathecal therapy on day 1 (weeks 18 and 22). Patients also receive methotrexate IM once a week and oral mercaptopurine daily on weeks 19-21, 23, and 24. On week 25, patients receive etoposide IV over 2 hours daily followed by cyclophosphamide IV over 30 minutes daily on days 1-5 and G-CSF SC or IV beginning on day 6 and continuing until blood counts recover. Patients receive an additional course of continuation therapy on weeks 28-35. On weeks 38-48, patients receive another identical course of continuation therapy with the exclusion of the etoposide and cyclophosphamide combination regimen.

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 annually thereafter.

Thompson PA, Murry DJ, Rosner GL, et al.: Methotrexate pharmacokinetics in infants with acute lymphoblastic leukemia. Cancer Chemother Pharmacol 59 (6): 847-53, 2007.[PUBMED Abstract]

Fernandez CV, Kodish E, Taweel S, et al.: Disclosure of the right of research participants to receive research results: an analysis of consent forms in the Children's Oncology Group. Cancer 97 (11): 2904-9, 2003.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

ZoAnn Dreyer, MD, Protocol chair		Ph: 832-822-4200 Email: zdreyer@bcm.tmc.edu

Registry Information
Official Title		INDUCTION INTENSIFICATION AND ALLOGENEIC BONE MARROW TRANSPLANT IN INFANT ALL: A PEDIATRIC ONCOLOGY GROUP PILOT STUDY Induction Intensification and Allogeneic Bone Marrow Transplant in Infant ALL: A Children's Oncology Group Pilot Study
Trial Start Date		1996-06-01
Registered in ClinicalTrials.gov		NCT00002756
Date Submitted to PDQ		1996-04-17
Information Last Verified		2006-10-21
NCI Grant/Contract Number		CA30969

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