Treatment of Childhood Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Treatment of Childhood Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00165087
• Other study ID #: 95-001
• Status: Terminated
• Phase: Phase 3
• First received: September 9, 2005
• Last updated: December 20, 2007
• Start date: January 1996
• Est. completion date: September 2006

Study information

• Verified date: December 2007
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to reduce the side-effects and discomfort of anti-leukemia therapy, to attain long-term control of the disease and to hopefully eradicate it.

Description:

• Children with acute lymphoblastic leukemia (ALL) are treated somewhat differently depending upon on the relative risk of the leukemia recurring. For this study they are classified into "Standard Risk", "High Risk" and "Infant/High Risk".

• The treatment for patients in the "Standard Risk" and "High Risk" groups consists of three phases of therapy: induction treatment; prevention of brain and spinal cord leukemia (CNS treatment); and intensification/continuation chemotherapy.

• The treatment for patients in the "Infant/High Risk" group consists of four phases of therapy: induction treatment; infant intensification therapy; intensification/continuation chemotherapy; and CNS treatment.

• The induction treatment consists of a combination of chemotherapy drugs whose purpose is to kill all detectable leukemia cells. This process usually requires a least one month and includes six anti-leukemia drugs. These drugs are: vincristine, doxorubicin, methotrexate, cytosine arabinoside, asparaginase and steroids (methylprednisolone or prednisone).

• After the induction phase, "Infant/High Risk" patients will receive a highly intensive month of treatment (infant intensification) . Drugs used during this month include high-dose methotrexate, asparaginase, 6-mercaptopurine and high dose cytosine arabinoside (ARA-C).

• CNS treatment begins during induction therapy but is intensified during the second and third month after diagnosis. Treatment for all patients will include a series of spinal taps with the instillation of anti-leukemia drugs, including cytosine arabinoside and methotrexate and with or without hydrocortisone (depending upon randomization).

• All high risk patients (those in both "High Risk" and "Infant/High Risk") as well as some standard risk patients will receive radiation treatment to the brain. Radiation therapy will either be given in either "conventional" treatments (once daily for 10 days), or "hyperfractionated" treatments (twice daily at half doses for 10 days). Total dose of radiation is 1800 cGy.

• Intensification and continuation therapy, begins 4-5 weeks after diagnosis for "Standard Risk" and "High Risk" groups and 4-5 weeks after infant intensification in "Infant/High Risk" group. This phase of treatment continues until the completion of two years of treatment. Patients in the "Standard Risk" group will receive five anti-leukemia drugs (vincristine, prednisone, methotrexate, asparaginase, and 6-mercaptopurine). Patients in "High Risk" and "Infant/High Risk" will receive six anti-leukemia drugs (vincristine, prednisone, doxorubicin, methotrexate, asparaginase and 6-mercaptopurine).

• All patients will be able to participate in a randomization comparing two types of asparaginase, E.coli and Erwinia. Patients will be randomized to receive either once weekly E.coli or once-weekly Erwinia during the Intensification phase, each given for a total of 20 weeks.

• Patients in the "Standard Risk" group are able to participate in an additional randomization. Standard risk patients will be randomized to receive one of two different regimens designed to prevent central nervous system leukemia, either 1)radiation therapy (given twice daily) with chemotherapy in the spinal fluid every 18 weeks, or 2) intensive chemotherapy in the spinal fluid alone without radiation.

• Patients in the "High Risk" and "Infant/High Risk" groups are able to participate in two randomizations in addition to the asparaginase randomization. The first will be to assess whether the drug dexrazoxane prevents heart damage caused by doxorubicin without affecting risk of relapse. Patients will be randomized to receive either doxorubicin alone or doxorubicin with dexrazoxane during the induction, CNS and intensification phases. The second randomization will compare the relative efficacy and toxicity of different cranial radiation schedules. Patients will be randomized to receive radiation in either once daily or twice daily fractions.

• Blood and bone marrow samples will be collected to learn more about the biology of leukemia. These samples will also be used to test minimal residual disease levels to learn if these levels help predict risk of relapse.

• Quality of life questionnaires will also be performed by the parents of patients, by children over eight, and by the child's clinician.

Other known NCT identifiers

• NCT00004034

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 491
• Est. completion date: September 2006
• Est. primary completion date: September 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 18 Years

Eligibility

Inclusion Criteria:

• Acute lymphoblastic leukemia, excluding known mature B-cell ALL

• < 18 years of age

• Patients who are leukopheresed or exchanged are eligible for study only after completion of the pheresis or exchange transfusion

• Absence of a t(8,14) (q24; q32), t (8,22), t(2,8)

• Total bilirubin < 1.4mg/dl

Exclusion Criteria:

• Known HIV positive

• Prior steroid therapy within 30 days of diagnosis

• Septic shock

• Ongoing intracranial hemorrhage

• Clinical evidence of CNS or lung leukostasis

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• asparaginase (E. Coli)

• asparaginase (Erwina)

• dexrazoxane

• doxorubicin

Procedure:
• cranial radiation (once daily fractionation)

• cranial radiation (twice-daily fractionation)

• Intrathecal chemotherapy without radiation

Locations

Country	Name	City	State
Canada	McMaster University	Hamilton	Ontario
Canada	Laval University	Montreal	Quebec
Canada	Sainte Justine Hosptial	Montreal	Quebec
Puerto Rico	San Jorge Children's Hospital	Santurce
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Maine Medical Center	Lewiston	Maine
United States	Ochsner Clinic	New Orleans	Louisiana
United States	Mt. Sinai Medical Center	New York	New York
United States	University of Rochester	Rochester	New York

Sponsors (2)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	Children's Hospital Boston

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico, 

References & Publications (5)

Goldberg JM, Silverman LB, Levy DE, Dalton VK, Gelber RD, Lehmann L, Cohen HJ, Sallan SE, Asselin BL. Childhood T-cell acute lymphoblastic leukemia: the Dana-Farber Cancer Institute acute lymphoblastic leukemia consortium experience. J Clin Oncol. 2003 Oct 1;21(19):3616-22. — View Citation

Lipshultz SE, Rifai N, Dalton VM, Levy DE, Silverman LB, Lipsitz SR, Colan SD, Asselin BL, Barr RD, Clavell LA, Hurwitz CA, Moghrabi A, Samson Y, Schorin MA, Gelber RD, Sallan SE. The effect of dexrazoxane on myocardial injury in doxorubicin-treated child — View Citation

Silverman LB, Declerck L, Gelber RD, Dalton VK, Asselin BL, Barr RD, Clavell LA, Hurwitz CA, Moghrabi A, Samson Y, Schorin MA, Lipton JM, Cohen HJ, Sallan SE. Results of Dana-Farber Cancer Institute Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1981-1995). Leukemia. 2000 Dec;14(12):2247-56. — View Citation

Silverman LB, Gelber RD, Dalton VK, Asselin BL, Barr RD, Clavell LA, Hurwitz CA, Moghrabi A, Samson Y, Schorin MA, Arkin S, Declerck L, Cohen HJ, Sallan SE. Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01. Blood. 2001 Mar 1;97(5):1211-8. — View Citation

Waber DP, Silverman LB, Catania L, Mautz W, Rue M, Gelber RD, Levy DE, Goldwasser MA, Adams H, Dufresne A, Metzger V, Romero I, Tarbell NJ, Dalton VK, Sallan SE. Outcomes of a randomized trial of hyperfractionated cranial radiation therapy for treatment o — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	-To evaluate the efficacy and safety of doxorubicin with or without dexrazoxane
Primary	-To determine the efficacy of hyperfractionated radiation plus standard intrathecal chemotherapy compared with intensive intrathecal chemotherapy alone in standard risk patients.
Primary	-To compare the relative efficacy and toxicity of E.coli and Erwinia asparaginase
Primary	-To compare the relative efficacy and toxicity of cranial radiation delivered in once-daily versus twice-daily fractions in high risk patinets.
Secondary	-To compare randomized treatment groups using health-related quality of life analyses.