Combination Chemotherapy With or Without Donor Bone Marrow Transplantation in Treating Infants With Previously Untreated Acute Lymphoblastic Leukemia

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00022126
First received: August 10, 2001
Last updated: February 18, 2014
Last verified: February 2014

August 10, 2001
February 18, 2014
November 2002
January 2005   (final data collection date for primary outcome measure)
Establish whether the CCG Augmented Regimen (AR) can be successfully administered in the infant age group [ Designated as safety issue: Yes ]
Not Provided
Complete list of historical versions of study NCT00022126 on ClinicalTrials.gov Archive Site
  • Grade 3 or 4 non-hematologic toxicity rates [ Designated as safety issue: Yes ]
  • Event-free survival [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Combination Chemotherapy With or Without Donor Bone Marrow Transplantation in Treating Infants With Previously Untreated Acute Lymphoblastic Leukemia
A Study of Modified Augmented BFM Therapy for Infants With Acute Lymphoblastic Leukemia

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Giving the drugs in different combinations may kill more cancer cells. Bone marrow transplantation allows the doctor to give higher doses of chemotherapy and kill more cancer cells.

PURPOSE: Phase II trial to compare the effectiveness of combination chemotherapy with or without donor bone marrow transplantation in treating infants who have previously untreated acute lymphoblastic leukemia.

OBJECTIVES:

  • Determine the feasibility of dexamethasone-based induction chemotherapy followed by augmented Berlin-Frankfurt-Munster (BFM) consolidation chemotherapy with or without allogeneic bone marrow transplantation in infants with previously untreated acute lymphoblastic leukemia.
  • Determine the event-free survival of patients treated with this regimen.
  • Determine the clinical prognostic features associated with outcome in these patients.
  • Compare the biologic characteristics of the leukemia cells with outcome in these patients.

OUTLINE: This is a multicenter study.

Patients receive induction therapy comprising oral dexamethasone 3 times daily on days 1-14; daunorubicin IV on days 1, 8, and 15; vincristine IV on days 1, 8, 15, and 22; and asparaginase intramuscularly (IM) on days 4, 6, 8, 11, 13, 15, 18, 20, and 22. Patients also receive methotrexate intrathecally (IT) on days 1, 8, and 15 (and days 4 and 22 for overt CNS disease).

Patients with M1 or M2 marrow after induction therapy receive augmented consolidation therapy when blood counts recover. Patients receive cyclophosphamide IV on days 1 and 29; cytarabine IV or subcutaneously (SC) on days 2-5, 9-12, 30-33, and 37-40; oral mercaptopurine on days 1-14 and 29-42; vincristine IV on days 15, 22, 43, and 50; pegaspargase IM on days 15 and 43; and methotrexate IT on days 1, 8, and 15.

Patients who do not receive bone marrow transplantation (BMT) proceed to interim maintenance #1 when blood counts recover. Patients receive methotrexate IT on days 1, 11, 22, and 32; methotrexate IV and vincristine IV on days 1, 11, 22, 32, and 43; and pegaspargase IM on days 2 and 23.

When blood counts recover, patients receive delayed intensification #1 comprising vincristine IV on days 1, 8, 15, 43, and 50; doxorubicin IV on days 1, 8, and 15; oral dexamethasone 3 times daily on days 1-7 and 15-21; pegaspargase IM on days 4 and 43; cyclophosphamide IV on day 29; methotrexate IT on days 29 and 36; oral thioguanine on days 29-42; and cytarabine IV or SC on days 30-33 and 37-40.

When blood counts recover, patients receive interim maintenance #2 comprising vincristine as in interim maintenance #1; methotrexate IT on day 1 and IV on days 1, 11, 22, 32, and 41; and pegaspargase IM on days 2 and 23.

When blood counts recover, patients receive delayed intensification #2 comprising vincristine, doxorubicin, dexamethasone, pegaspargase, cyclophosphamide, cytarabine, and thioguanine as in intensification #1. Patients also receive methotrexate IT on days 1 and 29.

When blood counts recover, patients receive maintenance therapy comprising methotrexate IT on day 1 and orally on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; vincristine IV on days 1, 29, and 57; oral dexamethasone 3 times daily on days 1-5, 29-33, and 57-61; and oral mercaptopurine daily. Treatment repeats every 84 days for 6 courses.

Patients with an allergy to pegaspargase replace it with asparaginase IM on the days after receiving methotrexate IV during interim maintenance #1 and #2 and daily over 6 days in place of each dose of pegaspargase during delayed intensification #1 and #2.

After augmented consolidation therapy, patients meeting the following criteria may receive BMT in place of chemotherapy:

  • In remission
  • Exhibiting chromosome translocation involving 11q23 or Ph+{(9;22)}
  • Available HLA-A, B, DR genotypic identical relative donor
  • No uncontrolled infection
  • Adequate organ function Within 3-4 weeks of consolidation therapy, patients undergoing allogeneic BMT receive cytarabine IV over 1 hour on days -8 to -5; cyclophosphamide IV over 30 minutes on days -7 and -6; and methylprednisolone IV twice daily on days -2 to 0. Patients also undergo total body irradiation twice daily on days -3 to 0. Patients receive allogeneic BMT on day 0. Patients also receive cyclosporine IV every 12 hours beginning on day -1, switching to oral when possible, and continuing until day 60. Patients then taper cyclosporine over the next 60-120 days.

Patients are followed every 2 months for 1 year, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1-2 years, and then annually thereafter.

PROJECTED ACCRUAL: A maximum of 20-40 patients will be accrued for this study within 2 years.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Leukemia
  • Drug: asparaginase
  • Drug: cyclophosphamide
  • Drug: cyclosporine
  • Drug: cytarabine
  • Drug: daunorubicin hydrochloride
  • Drug: dexamethasone
  • Drug: doxorubicin hydrochloride
  • Drug: mercaptopurine
  • Drug: methotrexate
  • Drug: methylprednisolone
  • Drug: pegaspargase
  • Drug: thioguanine
  • Drug: vincristine sulfate
  • Procedure: allogeneic bone marrow transplantation
  • Radiation: radiation therapy
Experimental: Modified Augmented BFM Therapy
Interventions:
  • Drug: asparaginase
  • Drug: cyclophosphamide
  • Drug: cyclosporine
  • Drug: cytarabine
  • Drug: daunorubicin hydrochloride
  • Drug: dexamethasone
  • Drug: doxorubicin hydrochloride
  • Drug: mercaptopurine
  • Drug: methotrexate
  • Drug: methylprednisolone
  • Drug: pegaspargase
  • Drug: thioguanine
  • Drug: vincristine sulfate
  • Procedure: allogeneic bone marrow transplantation
  • Radiation: radiation therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
6
April 2006
January 2005   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Diagnosis of previously untreated acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia

    • CNS or testicular disease allowed
  • No L3 sIg+ ALL or acute myelogenous leukemia
  • At least 36 weeks gestation for congenital ALL

PATIENT CHARACTERISTICS:

Age:

  • Under 366 days at diagnosis

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

  • Not specified

Renal:

  • Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • Not specified

Endocrine therapy:

  • Steroid therapy within 48 hours of study allowed if complete blood counts and lumbar puncture results known
  • No chronic steroid treatment for other disease

Radiotherapy:

  • Not specified

Surgery:

  • Not specified

Other:

  • No other concurrent cytotoxic therapy
Both
up to 1 Year
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada
 
NCT00022126
AALL01P1, COG-AALL01P1, CDR0000068787
Yes
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Study Chair: Paul S. Gaynon, MD Children's Hospital Los Angeles
Children's Oncology Group
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP