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A Study in Adults With Untreated Acute Lymphoblastic Leukemia

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ClinicalTrials.gov Identifier: NCT00136435
Recruitment Status : Active, not recruiting
First Posted : August 29, 2005
Last Update Posted : February 9, 2018
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

Study Description
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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.

Condition or disease Intervention/treatment 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

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : June 2002
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
Only Arm for this study
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 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.


Outcome Measures
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Primary Outcome Measures :
  1. 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 :
  1. To determine the safety and optimal dosing of L-asparaginase during the intensification period [ Time Frame: 5 years ]
  2. to determine the effect of weekly E. coli L-asparaginase by evaluating serum asparaginase levels in all patients [ Time Frame: 5 years ]
  3. to determine the safety of individualized dosing of E. coli L-asparaginase based upon asparaginase levels [ Time Frame: 5 years ]
  4. 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 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
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
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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
First Posted: August 29, 2005    Key Record Dates
Last Update Posted: February 9, 2018
Last Verified: February 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Daniel J. DeAngelo, MD, PhD, Dana-Farber Cancer Institute:
ALL
acute lymphoblastic leukemia
chemotherapy
asparaginase

Additional relevant MeSH terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Cortisol succinate
Dexamethasone
Prednisone
Hydrocortisone
 Doxorubicin
Methotrexate
Cytarabine
Vincristine
Asparaginase
6-Mercaptopurine
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists