The purpose of this study is to determine the safety and optimal dosing of l-asparaginase in adult patients with Acute Lymphoblastic Leukemia between the ages of 18 and 50 years.

Condition	Intervention	Phase
Acute Lymphoblastic Leukemia	Drug: prednisone  Drug: doxorubicin  Drug: vincristine  Drug: methotrexate  Drug: asparaginase  Drug: mercaptopurine  Drug: dexamethasone  Procedure: cranial radiation  Drug: leucovorin  Drug: cytarabine  Drug: hydrocortisone  Drug: 6-mercaptopurine (6-MP)	Phase II

Further Study Details: 

Primary Outcomes: To determine the feasibility, safety and efficacy of the high-risk pediatric treatment regimen in adult patients between the ages of 18 and 50 years.
Secondary Outcomes: To determine the safety and optimal dosing of L-asparaginase during the intensification period; to determine the effect of weekly E.coli L-asparaginase by evaluating serum asparaginase levels in all patients; to determine the safety of individualized dosing of E.coli L-asparaginase based upon asparaginase levels; to evaluate the outcome of patients based upon minimal residual disease status(MRD) after 28 days of multi-agent induction chemotherapy.
Expected Total Enrollment:  60

• This study has four treatment phases 1) induction, 2) central nervous system therapy, 3) intensification, and 4) continuation.
• The induction phase lasts one month and eight drugs are used during this phase of treatment. The drugs are administered as follows:

Prednisone; on day 1-28:

Vincristine; on day 1,8,15,and 22:

Doxorubicin; on days 1 and 2:

Methotrexate; on day 3;

Leucovorin; 36 hours after methotrexate:

Asparaginase; on day 5:

Intra-thecal Cytarabine; on days 1,15,and 29:

Intra-thecal Methotrexate/Hydrocortisone; on days 15 and 29

• A bone marrow aspirate and biopsy will be obtained on day 15 and day 29 of induction therapy. If on day 29 the patients bone marrow and peripheral blood counts are not in complete remission, than the patient may receive vincristine on days 29, 36 and 43. Bone marrow biopsy will be repeated weekly until complete remission is documented. If the patient does not achieve complete remission by day 49 they will be removed from the study.
• Central Nervous System (CNS) therapy begins immediately after the end of the induction therapy. This phase of treatment should last 3 weeks. Treatment includes a series of spinal taps with the instillation of anti-leukemia drugs. Four spinal taps will be performed over a two week period. Anti-leukemia drugs will also be given orally. The drugs given are as follows: Vincristine; on day 1: Doxorubicin; on day 1: 6-mercaptopurine (6-MP); on days 1-14: Intra-thecal Methotrexate/Cytarabine; 4 times over 2 weeks.
• Radiation therapy will be delivered in 10 daily treatments during the CNS phase of therapy.
• The intensification phase begins as soon as the CNS phase ends and lasts approximately 30 weeks. It consists of cycles of chemotherapy repeated every 3 weeks, along with asparaginase administered weekly. The drugs given are as follows: Vincristine; Day 1: Dexamethasone; days 1-5: 6-MP; days 1-14: Doxorubicin; day 1: Asparaginase; weekly: Methotrexate; weekly: Intra-thecal Hydrocortisone/Methotrexate/cytarabine; every 18 weeks.
• The continuation phase of treatment begins after the intensification phase. It consists of cycles of chemotherapy repeated every three weeks and will last until the patient is in remission for two years. The drugs given are: Vincristine; day 1 : Prednisone or Dexamethasone; days 1-5: 6-MP; days 1-14: Methotrexate; weekly: Intra-thecal Methotrexate/Cytarabine/Hydrocortisone: every 18 weeks.
• During this study blood tests will ber performed at the start of therapy, at day 29 post induction and at the time of each intrathecal therapy (every 18 weeks).
• Bone marrow biopsy/aspirate will be done days 15 and 29 of induction than every 6 months until completion.

Ages Eligible for Study:  18 Years   -   50 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Patients must have pathologically documented acute lymphoblastic leukemia, excluding mature B-cell ALL.
• No prior therapy for leukemia with the following exceptions:

up to one week of steroids; emergent leukapheresis; emergency treatment for hyperleukocytosis with hydroxyurea; cranial RT for CNS leukostasis (one dose only); emergent radiation therapy to the mediastinum.

• ECOG performance Status 0 to 2.
• Between the age of 18 to 50 years.

Exclusion Criteria:

• Uncontrolled active infection.
• Pregnancy or nursing mothers.
• Prior history of pancreatitis.
• Prior history of a cerebrovascular accident or hemorrhage.
• Evidence of infection with the Human Immunodeficiency Virus.
• Active psychiatric or mental illness making informed consent or careful clinical follow-up unlikely.
• The treating physician should consider all relevant medical and other considerations when deciding whether this protocol is appropriate for a particular patient.

Please refer to this study by ClinicalTrials.gov identifier  NCT00136435

Daniel J. DeAngelo, MD,PhD      617-632-2645    ddeangelo@partners.org
Ilene Galinsky, RN, NP      617-632-3902    igalinsky@partners.org

Massachusetts
      Dana-Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
      Massachusetts General Hospital, Boston,  Massachusetts,  02115,  United States; Recruiting

Study chairs or principal investigators

Daniel J. DeAngelo, MD, PhD,  Principal Investigator,  Dana-Farber Cancer Institute   

Study ID Numbers:  01-175
Last Updated:  August 26, 2005
Record first received:  August 25, 2005
ClinicalTrials.gov Identifier:  NCT00136435
Health Authority: United States: Institutional Review Board
ClinicalTrials.gov processed this record on 2005-08-30