A Study in Adults With Untreated Acute Lymphoblastic Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Brigham and Women's Hospital
Massachusetts General Hospital
Queen Elizabeth II Health Sciences Centre
Information provided by (Responsible Party):
Daniel J. DeAngelo, MD, PhD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00136435
First received: August 25, 2005
Last updated: January 2, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Acute Lymphoblastic Leukemia
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
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • 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 [ Time Frame: TBD ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the safety and optimal dosing of L-asparaginase during the intensification period [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • to determine the effect of weekly E. coli L-asparaginase by evaluating serum asparaginase levels in all patients [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • to determine the safety of individualized dosing of E. coli L-asparaginase based upon asparaginase levels [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: June 2002
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    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 Name: 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.
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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00136435

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02115
United States, New York
University Of Columbia Medical Center
New York, New York, United States
Canada, Manitoba
Manitoba Blood & Marrow Transplant Program CancerCare Manitoba
Winnipeg, Manitoba, Canada
Canada, Ontario
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
Canada, Quebec
Hospital Maisonneuve-Rosemont
Montreal, Quebec, Canada
Royal Victoria Hospital
Montreal, Quebec, Canada
Canada, Saskatchewan
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, Canada
Canada
Queen Elizabeth II
Halifax, Canada
Sponsors and Collaborators
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Massachusetts General Hospital
Queen Elizabeth II Health Sciences Centre
Investigators
Principal Investigator: Daniel J. DeAngelo, MD, PhD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Daniel J. DeAngelo, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00136435     History of Changes
Other Study ID Numbers: 01-175
Study First Received: August 25, 2005
Last Updated: January 2, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
ALL
acute lymphoblastic leukemia
chemotherapy
asparaginase

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
6-Mercaptopurine
Cytarabine
Methotrexate
Asparaginase
Dexamethasone
Doxorubicin
Prednisone
Vincristine
BB 1101
Dexamethasone acetate
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone
Dexamethasone 21-phosphate
Hydrocortisone-17-butyrate
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014