Clinical trial NCT00136435: A Study in Adults With Untreated Acute Lymphoblastic Leukemia
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 type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Acute Lymphoblastic Leukemia
Keywords: ALL
acute lymphoblastic leukemia
chemotherapy
asparaginase
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
name: Massachusetts General Hospital
name: Queen Elizabeth II Health Sciences Centre
First posted: 2005-08-29
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
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 outcomes:
measure: To determine the safety and optimal dosing of L-asparaginase during the intensification period
timeFrame: 5 years
measure: to determine the effect of weekly E. coli L-asparaginase by evaluating serum asparaginase levels in all patients
timeFrame: 5 years
measure: to determine the safety of individualized dosing of E. coli L-asparaginase based upon asparaginase levels
timeFrame: 5 years
measure: to evaluate the outcome of patients based upon minimal residual disease status (MRD) after 28 days of multi-agent induction chemotherapy
timeFrame: 5 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: University Of Columbia Medical Center
state: New York
city: Winnipeg
country: Canada
facility: Manitoba Blood & Marrow Transplant Program CancerCare Manitoba
state: Manitoba
city: Hamilton
country: Canada
facility: McMaster University Medical Center
state: Ontario
city: Kingston
country: Canada
facility: Queen's University
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: Hospital Maisonneuve-Rosemont
state: Quebec
city: Montreal
country: Canada
facility: Royal Victoria Hospital
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
city: Halifax
country: Canada
facility: Queen Elizabeth II
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Daniel J. DeAngelo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: