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Trial record 28 of 67 for:    "Acute Lymphocytic Leukemia" | "Hydrocortisone"

Treatment of Acute Lymphoblastic Leukemia in Children

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ClinicalTrials.gov Identifier: NCT00165178
Recruitment Status : Completed
First Posted : September 14, 2005
Last Update Posted : April 25, 2013
Sponsor:
Collaborators:
Boston Children’s Hospital
University of Rochester
McMaster University
San Jorge Children's Hospital (Puerto Rico)
St. Justine's Hospital
Maine Children's Cancer Program
Ochsner Health System
Tulane University School of Medicine
Laval University
Columbia University
Information provided by (Responsible Party):
Lewis B. Silverman, M.D., Dana-Farber Cancer Institute

Brief Summary:
The purpose of this study is to reduce the side-effects from anti-leukemia therapy. The therapy in this study is based upon treatment information learned from prior clinical research programs as well as from laboratory research.

Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Drug: prednisone Drug: dexamethasone Drug: doxorubicin Drug: E. coli asparaginase Drug: vincristine Drug: methotrexate Drug: Leucovorin Drug: Asparaginase Drug: cytarabine Drug: Methotrexate/Hydrocortisone Phase 3

Detailed Description:
  • Children with acute lymphoblastic leukemia are treated somewhat differently depending on the relative risk of the leukemia recurring. Patients will be separated into "Standard Risk" and "High Risk".
  • The treatment program for both groups is separated into 4 phases. The phases of treatment are induction, central nervous system (CNS) therapy, intensification and continuation.
  • The induction phase of therapy lasts for about one month and its purpose is to kill all detectable leukemia cells. Patients in both groups will receive the following medication: prednisone, vincristine, doxorubicin, methotrexate, leucovorin, asparaginase, cytarabine (ARA-C), and hydrocortisone. Patients in the "Hight Risk" group will also receive dexrazoxane.
  • Patients whose leukemia is found to have a specific genetic abnormality involving a gene on chromosome 11 (known as MLL gene) will have a MLL intensification phase which begins after complete remission and lasts about 1 month. The drugs involved in MLL intensification are: vincristine, methotrexate, leucovorin, hydrocortisone, cytarabine and L-asparaginase.
  • CNS therapy begins immediately after the end of induction therapy, after remission is documented. This phase of treatment should last 3 weeks and includes a series of spinal taps with the instillation of anti-leukemia drugs. Four spinal taps will be performed over a two-week period. Both groups will receive vincristine, 6-mercaptopurine and methotrexate/cytarabine/hydrocortisone. Patients in the "High Risk" group will also receive doxorubicin with dexrazoxane.
  • Radiation therapy will also be delivered to patients in the "High Risk" group during the CNS therapy phase. Radiation will be given in 8 daily treatments. The total dose of radiation used during this study is lower than what has been used in the past to help reduce side effects without increasing the risk of relapse.
  • The intensification phase begins after the CNS therapy ends and lasts for 30 weeks. This phase is intended to further reduce the number of leukemia cells in the body and consists of cycles of chemotherapy repeated every three weeks with weekly shots of asparaginase. The drugs administered to both groups during this phase are: prednisone or dexamethasone, vincristine,6-mercaptopurine, methotrexate, E. coli asparaginase and cytarabine. Patients in the "High Risk" group will also receive doxorubicin and dexrazoxane.
  • The continuation phase begins after the completion of the intensification phase and the goal is to eradicate all leukemia from the body. It consists of cycles of chemotherapy repeated every 3 weeks and is continued until the patient has been in remission for 2 years. The drugs administered during this phase are vincristine, prednisone or dexamethasone, 6-mercaptopurine, methotrexate and cytarabine.
  • During this trial there are two randomizations, each is between the "standard" treatment and the "investigational" treatment. One randomization involves the drug E. coli L-asparaginase and two ways of dosing this drug. One way is to give the same standard dose of the drug that has been administered for years. The other way is to start with a lower dose and measure the amount of the drug in the blood every 3 weeks adjusting the dose as necessary. The goal of doing this is to maintain adequate drug levels with lower doses in the hope the it may reduce some side effects of the drug.
  • The second randomization involves the drugs prednisone and dexamethasone. Both drugs have been used in the past to help treat ALL but it is not known if there is a difference between the two drugs, especially in terms of side effects. Patients will be randomized to either receive dexamethasone or prednisone.
  • Throughout the study blood tests, urine tests, spinal taps, and bone marrow tests will be performed to monitor the disease status, side effects from medications and other complications from therapy.
  • Quality of life questionnaires will also be performed by the patient (if older than 8), parent and patient's clinician.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 498 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Acute Lymphoblastic Leukemia in Children
Study Start Date : September 2000
Actual Primary Completion Date : December 2004
Actual Study Completion Date : May 2011


Arm Intervention/treatment
Experimental: Individualized ASP dose Drug: doxorubicin
Induction Phase: Intravenously on Days 0,1 Intensification Phase: Intravenously on Day 1 of each cycle
Other Name: dexrazoxane

Drug: E. coli asparaginase
Intensification Phase: In the muscle weekly. Dose will vary

Drug: vincristine
Induction: Intravenously on days 0, 7, 14, 21 MLL Intensification Phase: Intravenously on Days 1, 8, 15, 22 CNS Therapy: Intravenously on Day 1 Intensification Phase: Intravenously on day 1 of each cycle Continuation Phase: Intravenously on Day 1 of each cycle

Drug: methotrexate
Induction: Intravenously on Day 2 MLL Intensification: Intravenously on Days 1, 8 Intensification: (when doxorubicin completed) Intravenously or into the muscle weekly Continuation: Intravenously or into the muscle weekly

Drug: Leucovorin
Induction Phase: Intravenously or orally begins 36 hours after methotrexate MLL Intensification: Intravenously or orally begins 36 hours after methotrexate

Drug: cytarabine
Induction: Intrathecal on Days 0, 14, 28 MLL Intensification: Intravenously on Days 15, 16, 22, 23
Other Name: ARA-C

Drug: Methotrexate/Hydrocortisone
Induction: Intrathecal on Days 14, 28 MLL Intensification: Intrathecal on Days 2,9

Active Comparator: Fixed dose ASP Drug: doxorubicin
Induction Phase: Intravenously on Days 0,1 Intensification Phase: Intravenously on Day 1 of each cycle
Other Name: dexrazoxane

Drug: E. coli asparaginase
Intensification Phase: In the muscle weekly. Dose will vary

Drug: vincristine
Induction: Intravenously on days 0, 7, 14, 21 MLL Intensification Phase: Intravenously on Days 1, 8, 15, 22 CNS Therapy: Intravenously on Day 1 Intensification Phase: Intravenously on day 1 of each cycle Continuation Phase: Intravenously on Day 1 of each cycle

Drug: methotrexate
Induction: Intravenously on Day 2 MLL Intensification: Intravenously on Days 1, 8 Intensification: (when doxorubicin completed) Intravenously or into the muscle weekly Continuation: Intravenously or into the muscle weekly

Drug: Leucovorin
Induction Phase: Intravenously or orally begins 36 hours after methotrexate MLL Intensification: Intravenously or orally begins 36 hours after methotrexate

Drug: cytarabine
Induction: Intrathecal on Days 0, 14, 28 MLL Intensification: Intravenously on Days 15, 16, 22, 23
Other Name: ARA-C

Drug: Methotrexate/Hydrocortisone
Induction: Intrathecal on Days 14, 28 MLL Intensification: Intrathecal on Days 2,9

Experimental: Dexamethasone Drug: dexamethasone
Intensification Phase: Given orally days 1-5 of each cycle Continuation Phase: Given orally days 1-5 pf each cycle

Drug: doxorubicin
Induction Phase: Intravenously on Days 0,1 Intensification Phase: Intravenously on Day 1 of each cycle
Other Name: dexrazoxane

Drug: vincristine
Induction: Intravenously on days 0, 7, 14, 21 MLL Intensification Phase: Intravenously on Days 1, 8, 15, 22 CNS Therapy: Intravenously on Day 1 Intensification Phase: Intravenously on day 1 of each cycle Continuation Phase: Intravenously on Day 1 of each cycle

Drug: methotrexate
Induction: Intravenously on Day 2 MLL Intensification: Intravenously on Days 1, 8 Intensification: (when doxorubicin completed) Intravenously or into the muscle weekly Continuation: Intravenously or into the muscle weekly

Drug: Leucovorin
Induction Phase: Intravenously or orally begins 36 hours after methotrexate MLL Intensification: Intravenously or orally begins 36 hours after methotrexate

Drug: Asparaginase
Induction: Into the muscle on Day 4 MLL Intensification: Into the muscle on Days 16, 23

Drug: cytarabine
Induction: Intrathecal on Days 0, 14, 28 MLL Intensification: Intravenously on Days 15, 16, 22, 23
Other Name: ARA-C

Drug: Methotrexate/Hydrocortisone
Induction: Intrathecal on Days 14, 28 MLL Intensification: Intrathecal on Days 2,9

Active Comparator: Prednisone Drug: prednisone
Induction Phase: Given orally or intravenously Days 0-28 Intensification Phase: Given orally Days 1-5 of each cycle Continuation Phase: Given orally Days 1-5 of each cycle

Drug: doxorubicin
Induction Phase: Intravenously on Days 0,1 Intensification Phase: Intravenously on Day 1 of each cycle
Other Name: dexrazoxane

Drug: vincristine
Induction: Intravenously on days 0, 7, 14, 21 MLL Intensification Phase: Intravenously on Days 1, 8, 15, 22 CNS Therapy: Intravenously on Day 1 Intensification Phase: Intravenously on day 1 of each cycle Continuation Phase: Intravenously on Day 1 of each cycle

Drug: methotrexate
Induction: Intravenously on Day 2 MLL Intensification: Intravenously on Days 1, 8 Intensification: (when doxorubicin completed) Intravenously or into the muscle weekly Continuation: Intravenously or into the muscle weekly

Drug: Leucovorin
Induction Phase: Intravenously or orally begins 36 hours after methotrexate MLL Intensification: Intravenously or orally begins 36 hours after methotrexate

Drug: Asparaginase
Induction: Into the muscle on Day 4 MLL Intensification: Into the muscle on Days 16, 23

Drug: cytarabine
Induction: Intrathecal on Days 0, 14, 28 MLL Intensification: Intravenously on Days 15, 16, 22, 23
Other Name: ARA-C

Drug: Methotrexate/Hydrocortisone
Induction: Intrathecal on Days 14, 28 MLL Intensification: Intrathecal on Days 2,9




Primary Outcome Measures :
  1. To optimize dosing of E. coli L-asparaginase during the intensification period [ Time Frame: 5 years ]
  2. To determine the side effects of prednisone versus dexamethasone. [ Time Frame: 5 years ]

Secondary Outcome Measures :
  1. To compare randomized treatment groups using health-related, quality-of-life analysis [ Time Frame: 5 years ]


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Ages Eligible for Study:   1 Year to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Acute lymphoblastic leukemia excluding known mature B-cell ALL by the presence of any of the following: surface immunoglobulin, L3 morphology, t(8;14) (q24;q32), t(8;22) or t(2;8)
  • Age > 12 months but less than 18 years

Exclusion Criteria:

  • Prior therapy except, 1 week of steroids, or emergent radiation therapy to the mediastinum
  • Known HIV positive

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00165178


Locations
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United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Dana-Farber Cancer Institute
Boston Children’s Hospital
University of Rochester
McMaster University
San Jorge Children's Hospital (Puerto Rico)
St. Justine's Hospital
Maine Children's Cancer Program
Ochsner Health System
Tulane University School of Medicine
Laval University
Columbia University
Investigators
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Principal Investigator: Lewis Silverman, MD Dana-Farber Cancer Institute

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Lewis B. Silverman, M.D., Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00165178     History of Changes
Other Study ID Numbers: 00-001
First Posted: September 14, 2005    Key Record Dates
Last Update Posted: April 25, 2013
Last Verified: April 2013
Keywords provided by Lewis B. Silverman, M.D., Dana-Farber Cancer Institute:
Acute lymphoblastic leukemia in children
High Risk ALL
Standard Risk ALL
E. coli asparaginase
Additional relevant MeSH terms:
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hydrocortisone
Leukemia
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cytarabine
Dexamethasone
Dexamethasone acetate
Prednisone
Doxorubicin
Liposomal doxorubicin
Methotrexate
Vincristine
Asparaginase
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal