A Study in Adults With Untreated Acute Lymphoblastic Leukemia

NCT00136435 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 01-175
• Study Type: interventional
• Target: 100
• Locations: 2 countries
• Sites: 12

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.

Conditions

Acute Lymphoblastic Leukemia

Keywords

ALL; acute lymphoblastic leukemia; chemotherapy; asparaginase

Outcome Measures

Primary Outcomes (1)

• Asparaginase Completion Rate

  Feasibility based on the rate of asparaginase completion defined as the percentage of patients who, after having achieved a complete remission after induction therapy, complete all 30 doses of asparaginase as part of intensification therapy. Complete remission is defined as peripheral blood without lymphoblasts, a bone marrow with \<5% lymphoblasts, an antigen-presenting cell (APC) \> 1000/mm3, platelets \> 100,000/mm3, and no evidence of extramedullary leukemia.

  Assessed at the end of the 30-week post-induction treatment period or when the participant comes off treatment, whichever occurs first.

Secondary Outcomes (5)

• 4-year Disease-Free Survival

  Assessed continuously throughout the treatment period, and annually for 5 years following the completion of protocol treatment, (up to 5 years). Relevant for this measure is 4 years from the date of complete remission.

• 4-year Overall Survival

  Assessed continuously throughout the treatment period, and annually for 5 years following the completion of protocol treatment (unless the participant dies or is lost to follow-up). Median follow-up for the whole trial is 4.5 years (95% CI:4.1-5.0 years).

• 4-year Event-Free Survival

  Assessed continuously throughout the treatment period, and annually for 5 years following the completion of protocol treatment (unless the participant dies or is lost to follow-up). Median follow-up for the whole trial is 4.5 years (95% CI:4.1-5.0 years).

• Post-Induction Nadir Serum Asparaginase Activity Level

  Samples for nadir serum asparaginase activity levels were assayed prior to asparaginase dose given during post-induction, at Weeks 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, and 30.

• Number of Participants With Asparaginase-Related Toxicity

  Assessed on an ongoing basis (at least once every 3 months) while patient is on study, and including the treatment phases of Induction, CNS, Intensification, and Continuation. Treatment duration for this study was a median (range) of 507 days (0-1097).

Study Arms (1)

Only Arm for this study

OTHER

Only Arm for this study

Drug: prednisone; Drug: doxorubicin; Drug: vincristine; Drug: methotrexate; Drug: asparaginase; Drug: dexamethasone; Radiation: cranial radiation; Drug: leucovorin; Drug: cytarabine; Drug: hydrocortisone; Drug: 6-mercaptopurine (6-MP); Drug: e. coli L-asparaginase

Interventions

prednisone DRUG

Induction Phase: Given orally on days 1-28

Only Arm for this study

doxorubicin 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

Only Arm for this study

vincristine 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

Only Arm for this study

methotrexate 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

Only Arm for this study

asparaginase DRUG

Induction: Given into the muscle on day 5

Only Arm for this study

dexamethasone DRUG

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

Only Arm for this study

cranial radiation RADIATION

Given in 10 daily treatments during CNS therapy phase

Only Arm for this study

leucovorin DRUG

Induction: Given intravenously or orally 36 hours after methotrexate

Only Arm for this study

cytarabine 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

Also known as: Ara-C

Only Arm for this study

hydrocortisone DRUG

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

Only Arm for this study

6-mercaptopurine (6-MP) DRUG

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

Only Arm for this study

e. coli L-asparaginase DRUG

Intensification: Given in to the muscle weekly.

Only Arm for this study

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Brigham and Women's Hospital: collaborator
• Massachusetts General Hospital: collaborator
• Queen Elizabeth II Health Sciences Centre: collaborator

Study Sites (12)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

University Of Columbia Medical Center

New York, New York, United States

Location

Manitoba Blood & Marrow Transplant Program CancerCare Manitoba

Winnipeg, Manitoba, Canada

Location

McMaster University Medical Center

Hamilton, Ontario, Canada

Location

Queen's University

Kingston, Ontario, Canada

Location

London Health Sciences Centre

London, Ontario, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Location

Hospital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Location

Royal Victoria Hospital

Montreal, Quebec, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada

Location

Queen Elizabeth II

Halifax, Canada

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Prednisone; Doxorubicin; Vincristine; Methotrexate; Asparaginase; Dexamethasone; Leucovorin; Cytarabine; Hydrocortisone; Mercaptopurine

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Aminopterin; Pterins; Pteridines; Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Pregnadienetriols; Steroids, Fluorinated; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Coenzymes; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Sulfhydryl Compounds; Sulfur Compounds; Purines

Results Point of Contact

• Title: Dr. Dan DeAngelo
• Organization: Dana Farber Cancer Institute

Daniel_Deangelo@dfci.harvard.edu

617-582-8410

Study Officials

• Daniel J. DeAngelo, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 25, 2005
• First Posted: August 29, 2005
• Study Start: June 1, 2002
• Primary Completion: November 1, 2008
• Study Completion: May 1, 2011
• Last Updated: October 20, 2025
• Results First Posted: October 20, 2025

Record last verified: 2025-10

Locations

CA (9); US (3)