A Study in Adults With Untreated Acute Lymphoblastic Leukemia

NCT ID: NCT00136435

Last Updated: 2025-10-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-06-30
• Study Completion Date: 2011-05-31

Brief Summary

The purpose of this study is to determine the safety and optimal dosing of L-asparaginase in adult patients with acute lymphoblastic leukemia (ALL) between the ages of 18 and 50 years.

Detailed Description

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 days 1-28:
• Vincristine; on days 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, then 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 (RT) 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 be performed at the start of therapy, at day 29 post induction and at the time of each intra-thecal therapy (every 18 weeks).

Bone marrow biopsy/aspirate will be done days 15 and 29 of induction, then every 6 months until completion.

Conditions

Acute Lymphoblastic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Only Arm for this study

Only Arm for this study

Group Type: OTHER

prednisone

Intervention Type: DRUG

Induction Phase: Given orally on days 1-28

doxorubicin

Intervention Type: DRUG

Induction Phase: Given intravenously on day 1 and day 2 CNS Therapy: Given intravenously on day 1 Intensification: Given day 1 of each cycle

vincristine

Intervention Type: DRUG

Induction: Given intravenously on days 1, 8, 15, and 22. If complete remission not achieved, will be given on days 29, 36 and 43.

CNS Therapy: Given intravenously on day 1. Intensification: Given intravenously on day 1 of each cycle. Continuation: Given intravenously on day 1 of each cycle

methotrexate

Intervention Type: DRUG

Induction: Given intravenously on day 3. CNS Therapy: Given intrathecally 4 times over two weeks Intensification: Given intrathecally every 18 weeks Continuation: Given intravenously weekly and intrathecally every 18 weeks

asparaginase

Intervention Type: DRUG

Induction: Given into the muscle on day 5

dexamethasone

Intervention Type: DRUG

Intensification: Given orally on days 1-5 of each cycle

cranial radiation

Intervention Type: RADIATION

Given in 10 daily treatments during CNS therapy phase

leucovorin

Intervention Type: DRUG

Induction: Given intravenously or orally 36 hours after methotrexate

cytarabine

Intervention Type: DRUG

Induction: Given intrathecally days 1, 15, 29 CNS Therapy: Given intrathecally 4 times over 2 weeks Intensification: Given intrathecally every 18 weeks Continuation: Given intrathecally every 18 weeks

hydrocortisone

Intervention Type: DRUG

Induction: Given intrathecally on days 15 and 29. Intensification: Given intrathecally every 18 weeks. Continuation: Given intrathecally every 18 weeks.

6-mercaptopurine (6-MP)

Intervention Type: DRUG

CNS Therapy: Taken orally on days 1-14. Intensification: Taken orally on days 1-14. Continuation: Taken orally on days 1-14.

e. coli L-asparaginase

Intervention Type: DRUG

Intensification: Given in to the muscle weekly.

Interventions

prednisone

Induction Phase: Given orally on days 1-28

Intervention Type: DRUG

doxorubicin

Induction Phase: Given intravenously on day 1 and day 2 CNS Therapy: Given intravenously on day 1 Intensification: Given day 1 of each cycle

Intervention Type: DRUG

vincristine

Induction: Given intravenously on days 1, 8, 15, and 22. If complete remission not achieved, will be given on days 29, 36 and 43.

CNS Therapy: Given intravenously on day 1. Intensification: Given intravenously on day 1 of each cycle. Continuation: Given intravenously on day 1 of each cycle

Intervention Type: DRUG

methotrexate

Induction: Given intravenously on day 3. CNS Therapy: Given intrathecally 4 times over two weeks Intensification: Given intrathecally every 18 weeks Continuation: Given intravenously weekly and intrathecally every 18 weeks

Intervention Type: DRUG

asparaginase

Induction: Given into the muscle on day 5

Intervention Type: DRUG

dexamethasone

Intensification: Given orally on days 1-5 of each cycle

Intervention Type: DRUG

cranial radiation

Given in 10 daily treatments during CNS therapy phase

Intervention Type: RADIATION

leucovorin

Induction: Given intravenously or orally 36 hours after methotrexate

Intervention Type: DRUG

cytarabine

Induction: Given intrathecally days 1, 15, 29 CNS Therapy: Given intrathecally 4 times over 2 weeks Intensification: Given intrathecally every 18 weeks Continuation: Given intrathecally every 18 weeks

Intervention Type: DRUG

hydrocortisone

Induction: Given intrathecally on days 15 and 29. Intensification: Given intrathecally every 18 weeks. Continuation: Given intrathecally every 18 weeks.

Intervention Type: DRUG

6-mercaptopurine (6-MP)

CNS Therapy: Taken orally on days 1-14. Intensification: Taken orally on days 1-14. Continuation: Taken orally on days 1-14.

Intervention Type: DRUG

e. coli L-asparaginase

Intensification: Given in to the muscle weekly.

Intervention Type: DRUG

Other Intervention Names

Ara-C

Eligibility 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.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
• Between the ages 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Queen Elizabeth II Health Sciences Centre

OTHER

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Daniel J. DeAngelo, MD, PhD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Daniel J. DeAngelo, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University Of Columbia Medical Center

New York, New York, United States

Manitoba Blood & Marrow Transplant Program CancerCare Manitoba

Winnipeg, Manitoba, Canada

McMaster University Medical Center

Hamilton, Ontario, Canada

Queen's University

Kingston, Ontario, Canada

London Health Sciences Centre

London, Ontario, Canada

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Hospital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Royal Victoria Hospital

Montreal, Quebec, Canada

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada

Queen Elizabeth II

Halifax, , Canada

Countries

United States; Canada

Other Identifiers

01-175

Identifier Type: -

Identifier Source: org_study_id