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Acute Lymphoblastic LeukemiaPhase 2NCT00136435

A Study in Adults With Untreated Acute Lymphoblastic Leukemia

A Phase 2 study testing prednisone, doxorubicin and vincristine in people with Acute Lymphoblastic Leukemia, run by Dana-Farber Cancer Institute at 12 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 50 years
Conditions the study is for
Acute Lymphoblastic Leukemia
What is being tested?
prednisone, doxorubicin and vincristine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
12 sitesin 2 countries
Study dates
Jun 2002to May 2011
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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);
Show all 9Show fewer
  • emergent radiation therapy to the mediastinum.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
  • Between the ages of 18 to 50 years.

Who cannot join

  • 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.

Trial locations and contacts

12 sites in 2 countries.

12 sites in 2 countries

Canada9 sites

  • Queen Elizabeth II

    Halifax

  • McMaster University Medical Center

    Hamilton, Ontario

  • Queen's University

    Kingston, Ontario

  • London Health Sciences Centre

    London, Ontario

  • Hospital Maisonneuve-Rosemont

    Montreal, Quebec

  • Royal Victoria Hospital

    Montreal, Quebec

  • Saskatoon Cancer Centre

    Saskatoon, Saskatchewan

  • Sunnybrook Health Sciences Centre

    Toronto, Ontario

  • Manitoba Blood & Marrow Transplant Program CancerCare Manitoba

    Winnipeg, Manitoba

Other trials in Canada

United States3 sites

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Massachusetts General Hospital

    Boston, Massachusetts, 02115

  • University Of Columbia Medical Center

    New York, New York

Other trials in United States

About this study

Official title: A Multicenter Phase II Study in Adults With Untreated Acute Lymphoblastic Leukemia: Testing Pharmacokinetically Individualized Doses of L-Asparaginase Following the Dana Farber Cancer Institute (DFCI) Pediatric Consortium Protocol

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.

Read the 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.

Being tested
prednisone, doxorubicin, vincristine, methotrexate, asparaginase
Keywords
ALL, acute lymphoblastic leukemia, chemotherapy, asparaginase
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • prednisoneDrug

    Induction Phase: Given orally on days 1-28

  • doxorubicinDrug

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

  • vincristineDrug

    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

  • methotrexateDrug

    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

  • asparaginaseDrug

    Induction: Given into the muscle on day 5

  • dexamethasoneDrug

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

  • cranial radiationRadiation

    Given in 10 daily treatments during CNS therapy phase

  • leucovorinDrug

    Induction: Given intravenously or orally 36 hours after methotrexate

  • cytarabineDrug

    Also called Ara-C

    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

  • hydrocortisoneDrug

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

  • 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.

  • e. coli L-asparaginaseDrug

    Intensification: Given in to the muscle weekly.

Study groups in NCT00136435
Study groupRoleWhat they receive
Only Arm for this studyOtherOnly Arm for this study
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. 4-year Disease-Free Survival

    Disease-Free Survival (DFS) based on the Kaplan-Meier method is defined as the time from achieving a complete remission to the first of disease recurrence or death, censored at time of last disease assessment. 4-year DFS is the percent probability of patients remaining alive, relapse-free and without occurrence of second malignant neoplasm 4 years from complete remission. Disease relapse is defined as >25% lymphoblasts identified morphologically in bone marrow aspirate/biopsy, or identification of lymphoblasts in marrow (any percentage) identified to be leukemic by flow cytometry, cytogenetics, fluorescent in situ hybridization (FISH), immunohistochemistry, or other tests. Appearance of leukemic cells at any extramedullary site (a single, unequivocal lymphoblast in the cerebrospinal fluid (CSF) may qualify as CNS leukemia) also qualifies if confirmed by the PI.

    Measured: 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.

  2. 4-year Overall Survival

    Overall Survival (OS) based on the Kaplan-Meier method is defined as the time from study entry to death from any cause, and will be censored the date last known alive. 4-year OS is the percent probability of patients remaining alive 4 years from study entry.

    Measured: 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).

  3. 4-year Event-Free Survival

    Event-Free Survival (EFS) based on the Kaplan-Meier method is defined as the time from study entry to the first event of death during induction therapy, failure to achieve CR at the end of induction, death during remission, or relapse. 4-year EFS is the percent probability of patients remaining alive, relapse-free and without occurrence of second malignant neoplasm 4 years from study entry. Patients not achieving a CR will be considered events at time zero. EFS will be censored at time of last disease assessment. Disease relapse is defined as >25% lymphoblasts identified morphologically in bone marrow aspirate/biopsy, or identification of lymphoblasts in marrow (any percentage) identified to be leukemic by flow cytometry, cytogenetics, FISH, immunohistochemistry, or other tests. Appearance of leukemic cells at any extramedullary site (a single, unequivocal lymphoblast in the CSF may qualify as CNS leukemia) also qualifies if confirmed by the PI.

    Measured: 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. Post-Induction Nadir Serum Asparaginase Activity Level

    Nadir serum asparaginase activity (NSAA) levels were estimated based on established methods.

    Measured: 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.

  5. Number of Participants With Asparaginase-Related Toxicity

    Asparaginase-related toxicity rate is defined as the percentage of patients who experience allergy (all grades), pancreatitis, thrombotic or bleeding complications, bone fracture, or avascular necrosis based on Common Terminology Criteria for Adverse Events (CTCAE) v2.

    Measured: 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).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Aug 2005 (estimated)
  2. Study startJun 2002
  3. Primary completionNov 2008
  4. Study completionMay 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00136435
Sponsor's protocol ID
01-175
Status last verified
Oct 2025
First submitted
25 Aug 2005
Last updated
20 Oct 2025
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing prednisone, doxorubicin and vincristine in people with Acute Lymphoblastic Leukemia, run by Dana-Farber Cancer Institute at 12 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in Canada, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Asparaginase Completion Rate (time frame: Assessed at the end of the 30-week post-induction treatment period or when the participant comes off treatment, whichever occurs first.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00136435.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2025.

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