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ALL Adult Consortium Trial: Adult ALL Trial

Registration Number
NCT00476190
Lead Sponsor
Dana-Farber Cancer Institute
Brief Summary

The purpose of this study is to determine the safety and effectiveness of a multi-drug chemotherapy regimen in adult patients with Acute Lymphoblastic Leukemia (ALL). We will use a regimen that is often used in pediatric patients and we will add drugs called PEG-asparaginase and E. coli asparaginase. PEG-asparaginase has been given as an injection in the past and has been used in treatment with both children and adults with ALL. Information from those other research studies suggests that intravenous PEG-asparaginase has been administered safely in both children and adults. We hope to gain more information about the participants disease and how it responds to standard chemotherapy drugs used to treat ALL\>

Detailed Description

* This study has several periods of treatment called phases and uses several different drugs in each phase. The drugs may be given by mouth, into a vein, or into the spinal fluid (called intrathecal chemotherapy). In some individuals this treatment helps prevent leukemia cells from coming back in the spinal fluid and brain. Radiation therapy will also be administered as part of this treatment regimen.

* The treatment program consists of 2-different treatment arms with six separate phases of therapy. The phases of treatment are: (1) Steroid prophase (2) Induction (3) Consolidation I (4) Central nervous system (CNS) therapy (5) Consolidation II (6) Continuation.

* The participants treatment arm will depend on the status of their leukemia at the end of the induction therapy (the second phase of treatment). Arm A: all participants who achieve complete remission after Induction and Arm B: all participants who fail to achieve a complete remission after Induction.

* Steroid Prophase: All participants are involved in this treatment phase which consists of two drugs, one given intravenously (IV) and one given intrathecally. This phase lasts 3 days and the purpose is to collect scientific data that might be useful in the future and to see how steroids work in treating leukemia

* Induction: This phase begins immediately after the steroid prophase and lasts about 1 month. Induction is used to cause a remission. Eight drugs are used during this phase of treatment, and administration is either orally, IV or intrathecal. On day 29, participant's bone marrow and peripheral blood counts will be tested. If they have achieved complete remission or partial remission, they will proceed to the next phase of treatment. If they are not in complete remission, they will receive vincristine by IV on days 32, 39 and 46, until complete remission is achieved. If they do not achieve complete or partial remission by day 53 they will be removed from the study.

* Consolidation I: This phase of treatment begins as soon as there is a documented confirmation that the participant's leukemia is either in complete or partial remission. Treatment in this phase lasts about 7 weeks and is intended to further reduce the number of leukemia cells in the body. This consolidation treatment consists of 3 phases: 1A, 1B and 1C. Each phase involves a three week cycle of chemotherapy. Arm A and Arm B will be assigned according to remission status after induction therapy and will determine the order that the participant follows the Consolidation phases.

* Central Nervous System (CNS) Therapy: CNS therapy begins 3 weeks after the end of Consolidation I therapy and should last 3 weeks. Treatment includes a series of lumbar punctures with the administration of anti-leukemia drug as well as oral drugs and IV drugs. Radiation therapy will also be given during this phase of therapy. The purpose of radiation therapy is to prevent leukemia from coming back in the brain. Radiation therapy will be given in either 8 or 10 daily treatments.

* Consolidation II Therapy: This phase begins as soon as CNS therapy ends and lasts about 27-30 weeks. It consists of cycles of chemotherapy repeated every three weeks along with IV PEG-asparaginase administered every 3 weeks. The cycles will be repeated until the participant receives a total of 10 doses of asparaginase.

* Continuation Therapy: This phase begins after the end of the Consolidation II phase. The goal of this phase is to get rid of all leukemia in the body. It consists of cycles of chemotherapy repeated every three weeks and will last until the participant has been in remission for two years.

* During all phases of treatment, participants will have tests and procedures to monitor their health and for research purposes.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
112
Inclusion Criteria
  • Acute lymphoblastic leukemia, excluding known mature B-cell ALL by the presence of any of the following: surface immunoglobulin, L3 morphology, t(8;14)(q24;q32), t(8;22), or t(2;8)
  • Age 18.00-50.99 years
Exclusion Criteria
  • Prior anti-leukemic therapy except 1 week or less of steroids, and/or emergent radiation therapy to the mediastinum, or hydroxyurea or emergent leukopheresis
  • Known HIV positive
  • Secondary ALL
  • Pregnant or breast feeding women
  • Patients with an active psychiatric or mental illness making informed consent or careful clinical follow-up unlikely

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm ACytarabineComplete remission achieved after Induction Phase
Arm AE. coli AsparaginaseComplete remission achieved after Induction Phase
Arm ARadiation TherapyComplete remission achieved after Induction Phase
Arm BRadiation TherapyFailure to achieve complete remission after the Induction Phase
Arm BE. coli AsparaginaseFailure to achieve complete remission after the Induction Phase
Arm ACyclophosphamideComplete remission achieved after Induction Phase
Arm BEtoposideFailure to achieve complete remission after the Induction Phase
Arm ADoxorubicinComplete remission achieved after Induction Phase
Arm AMethotrexateComplete remission achieved after Induction Phase
Arm AMethylprednisoneComplete remission achieved after Induction Phase
Arm AVincristineComplete remission achieved after Induction Phase
Arm AHydrocortisone Sodium SuccinateComplete remission achieved after Induction Phase
Arm APEG-AsparaginaseComplete remission achieved after Induction Phase
Arm ADexamethasoneComplete remission achieved after Induction Phase
Arm A6-MPComplete remission achieved after Induction Phase
Arm AImatinibComplete remission achieved after Induction Phase
Arm AEtoposideComplete remission achieved after Induction Phase
Arm BDoxorubicinFailure to achieve complete remission after the Induction Phase
Arm BCyclophosphamideFailure to achieve complete remission after the Induction Phase
Arm BMethylprednisoneFailure to achieve complete remission after the Induction Phase
Arm BCytarabineFailure to achieve complete remission after the Induction Phase
Arm BMethotrexateFailure to achieve complete remission after the Induction Phase
Arm BVincristineFailure to achieve complete remission after the Induction Phase
Arm BHydrocortisone Sodium SuccinateFailure to achieve complete remission after the Induction Phase
Arm BDexamethasoneFailure to achieve complete remission after the Induction Phase
Arm BPEG-AsparaginaseFailure to achieve complete remission after the Induction Phase
Arm B6-MPFailure to achieve complete remission after the Induction Phase
Arm BImatinibFailure to achieve complete remission after the Induction Phase
Primary Outcome Measures
NameTimeMethod
To evaluate the feasibility of administering PEG asparaginase in the adult ALL population.3 years

Measured as the percentage of patients who, after having achieved a CR after induction therapy, complete \>25 weeks of IV PEG asparaginase as part of intensification therapy.

To evaluate toxicity of administering PEG asparaginase in the adult ALL population.3 years

Measured as frequencies of grade III or higher adverse events.

Secondary Outcome Measures
NameTimeMethod
Overall survival, defined as time from study entry to death from any cause, will be estimated using Kaplan-Meier methods.3 years
To determine the complete response rate at the end of induction therapy.2 years
Disease-free survival, defined as the time from achieving a complete remission to the first of disease recurrence or death, will be estimated using Kaplan-Meier methods.3 years

Trial Locations

Locations (15)

Ohio State University Medical Center

🇺🇸

Columbus, Ohio, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Children's Hospital of Boston

🇺🇸

Boston, Massachusetts, United States

Beth Isreal Deaconess Medical Center

🇺🇸

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

The Moncton Hospital

🇨🇦

Moncton, New Brunswick, Canada

LDS Hospital

🇺🇸

Salt Lake City, Utah, United States

Hopital Charles LeMoyne

🇨🇦

Greenfield Park, Quebec, Canada

Hopital Maisonneuve Rosemont

🇨🇦

Montreal, Quebec, Canada

Hopital Notre-Dame

🇨🇦

Montreal, Quebec, Canada

Vancouver Cancer Center

🇨🇦

Vancouver, British Columbia, Canada

McGill University Department of Oncology

🇨🇦

Montreal, Quebec, Canada

Cancer Care Manitoba

🇨🇦

Winnipeg, Manitoba, Canada

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

🇺🇸

New York, New York, United States

QEII, Health Sciences Centre

🇨🇦

Halifax, Nova Scotia, Canada

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