A Study in Adults With Untreated Acute Lymphoblastic Leukemia

Sponsor

Dana-Farber Cancer Institute (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00136435

Collaborator

Brigham and Women's Hospital (Other), Massachusetts General Hospital (Other), Queen Elizabeth II Health Sciences Centre (Other)

100

Enrollment

Locations

Arm

253

Duration (Months)

8.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

N/A

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 :

Jun 1, 2002

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Other: 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 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.

Arm

Intervention/Treatment

Other: 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 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.

Outcome Measures

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 []

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
2	Massachusetts General Hospital	Boston	Massachusetts	United States	02115
3	University Of Columbia Medical Center	New York	New York	United States
4	Manitoba Blood & Marrow Transplant Program CancerCare Manitoba	Winnipeg	Manitoba	Canada
5	McMaster University Medical Center	Hamilton	Ontario	Canada
6	Queen's University	Kingston	Ontario	Canada
7	London Health Sciences Centre	London	Ontario	Canada
8	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada
9	Hospital Maisonneuve-Rosemont	Montreal	Quebec	Canada
10	Royal Victoria Hospital	Montreal	Quebec	Canada
11	Saskatoon Cancer Centre	Saskatoon	Saskatchewan	Canada
12	Queen Elizabeth II	Halifax		Canada