A Study in Adults With Untreated Acute Lymphoblastic Leukemia

April 16, 2024 updated by: Daniel J. DeAngelo, MD, PhD, Dana-Farber Cancer Institute

A Multicenter Phase II Study in Adults With Untreated Acute Lymphoblastic Leukemia: Testing Pharmacokinetically Individualized Doses of L-Asparaginase Following the 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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
      • Halifax, Canada
        • Queen Elizabeth II
    • Manitoba
      • Winnipeg, Manitoba, Canada
        • Manitoba Blood & Marrow Transplant Program CancerCare Manitoba
    • Ontario
      • Hamilton, Ontario, Canada
        • McMaster University Medical Center
      • Kingston, Ontario, Canada
        • Queen's University
      • London, Ontario, Canada
        • London Health Sciences Centre
      • Toronto, Ontario, Canada
        • Sunnybrook Health Sciences Centre
    • Quebec
      • Montreal, Quebec, Canada
        • Hospital Maisonneuve-Rosemont
      • Montreal, Quebec, Canada
        • Royal Victoria Hospital
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada
        • Saskatoon Cancer Centre
  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02115
        • Massachusetts General Hospital
    • New York
      • New York, New York, United States
        • University Of Columbia Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Only Arm for this study
Drug: prednisone
Induction Phase: Given orally on days 1-28
Drug: doxorubicin
Induction Phaese: Given intravenously on day 1 and day 2 CNS Therapy: Given intravenously on day 1 Intensification: Given day 1 of each cycle
Drug: vincristine

Induction: Given intravenously on days 1, 8, 15, and 22. If complete remission not acheived, 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

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
Drug: asparaginase
Induction: Given into the muscle on day 5
Drug: dexamethasone
Intensification: Given orally on days 1-5 of each cycle
Radiation: cranial radiation
Given in 10 daily treatments during CNS therapy phase
Drug: leucovorin
Induction: Given intravenously or orally 36 hours after methotrexate
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
Other Names:
  • Ara-C
Drug: hydrocortisone
Induction: Given intrathecally on days 15 and 29. Intensification: Given intrathecally every 18 weeks. Continuation: Given intrathecally every 18 weeks.
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.
Drug: e. coli L-asparaginase
Intensification: Given in to the muscle weekly.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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 Outcome Measures

Outcome Measure
Time Frame
To determine the safety and optimal dosing of L-asparaginase during the intensification period
Time Frame: 5 years
5 years
to determine the effect of weekly E. coli L-asparaginase by evaluating serum asparaginase levels in all patients
Time Frame: 5 years
5 years
to determine the safety of individualized dosing of E. coli L-asparaginase based upon asparaginase levels
Time Frame: 5 years
5 years
to evaluate the outcome of patients based upon minimal residual disease status (MRD) after 28 days of multi-agent induction chemotherapy
Time Frame: 5 years
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dana-Farber Cancer Institute

Collaborators

Massachusetts General Hospital
Brigham and Women's Hospital
Queen Elizabeth II Health Sciences Centre

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2002

Primary Completion (Actual)

January 1, 2024

Study Completion (Estimated)

July 1, 2024

Study Registration Dates

First Submitted

August 25, 2005

First Submitted That Met QC Criteria

August 25, 2005

First Posted (Estimated)

August 29, 2005

Study Record Updates

Last Update Posted (Actual)

April 17, 2024

Last Update Submitted That Met QC Criteria

April 16, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 01-175

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Acute Lymphoblastic Leukemia

Clinical Trials on prednisone

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Senegal

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe