ALL Adult Consortium Trial: Adult ALL Trial

NCT ID: NCT00476190

Last Updated: 2025-06-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 112 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-30
• Study Completion Date: 2020-03-31

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.

Conditions

Acute Lymphoblastic Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pre-amendment cohort, 2500 IU/m2 q2 weeks

The first 66 patients enrolled under the initial design. In the post-induction phases, IV asparaginase was administered every two weeks at the higher dose of 2500 IU/m2, for a total of 30 post-induction weeks. IV asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.

Group Type: EXPERIMENTAL

Doxorubicin

Intervention Type: DRUG

Induction: Intravenously on days 4 and 5. Consolidation 1A: Intravenously on day 1. CNS Therapy: Intravenously on day 1. Consolidation II: Intravenously day 1 of each cycle.

Cytarabine

Intervention Type: DRUG

Prophase: Intravenously on days 1-3. Induction: Intrathecal on days 15 or 18. Consolidation IB: Intravenously or subcutaneous on days 2-5 and 9-12. Consolidation IC: Intravenously every 12 hours starting on day 1 CNS Therapy: Intrathecal 4 times over 2 weeks. Consolidation II: Intrathecal once every 18 weeks Continuation: Intrathecal every 18 weeks

Methotrexate

Intervention Type: DRUG

Induction: Intravenously on day 6 and intrathecally on day 29 or 32. Consolidation IA: Intravenously on day 1 and intrathecally on Day 1 (prior to IV).

Consolidation IB: Intrathecally on day 1. CNS Therapy: Intrathecally 4 times over 2 weeks. Consolidation: Intrathecally once every 18 weeks. Continuation: Intravenously weekly and intrathecally every 18 weeks.

Vincristine

Intervention Type: DRUG

Induction: Intravenously on days 4, 11, 18, 25. Consolidation IA: Intravenously on day 1. CNS Therapy: Intravenously on day 1. Consolidation II: Intravenously on day 1 of each cycle.

Cyclophosphamide

Intervention Type: DRUG

Consolidation IB: Intravenously on day 1

Methylprednisone

Intervention Type: DRUG

Prophase: Intravenously on days 1-3

Hydrocortisone Sodium Succinate

Intervention Type: DRUG

Induction: Intrathecally on day 15 or 18. CNS Therapy: Intrathecally 4 times over 2 weeks. Consolidation II: Intrathecally once every 18 weeks. Continuation: Intrathecally every 18 weeks.

Dexamethasone

Intervention Type: DRUG

Consolidation IC: Orally on days 1-5 twice per day. Consolidation II: Orally on days 1-5 of each cycle. Continuation: Orally on days 1-5 of each cycle.

6-MP

Intervention Type: DRUG

Induction: Orally on days 3-43 or 33-46. Consolidation IA: orally on days 1-14. Consolidation IB: orally on days 1-14. CNS Therapy: Orally on days 1-14. Consolidation II: Orally on days 1-14. Continuation: Orally on days 1-14 of each cycle.

PEG-Asparaginase

Intervention Type: DRUG

Consolidation IC: Intravenously every 3 weeks, starting on day 8. CNS Therapy: Intravenously every 3 weeks, starting 3 weeks after the Consolidation IC dose.

Consolidation II: Intravenously every 3 weeks.

Imatinib

Intervention Type: DRUG

Used for PH+ ALL subjects enrolled prior to May 1st 2011 only and is used continuously throughout every phase of treatment.

Etoposide

Intervention Type: DRUG

Consolidation IC: intravenously on days 3, 4 and 5 of this cycle.

Radiation Therapy

Intervention Type: PROCEDURE

Given during CNS Therapy either 8 or 10 daily treatments, on days 1-8 or 1-10, depending upon leukemia involvement in the CSF

E. coli Asparaginase

Intervention Type: DRUG

Intramuscularly Day 7 of Induction.

Post-amendment cohort, 2000 IU/m2 q3 weeks

The 46 patients enrolled under amended design, after August 1, 2011. In the post-induction phases, IV asparaginase was administered every 3 weeks at the dose of 2000 IU/m2, for a total of 30 post-induction weeks. E. coli asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.

Group Type: EXPERIMENTAL

Doxorubicin

Intervention Type: DRUG

Induction: Intravenously on days 4 and 5. Consolidation 1A: Intravenously on day 1. CNS Therapy: Intravenously on day 1. Consolidation II: Intravenously day 1 of each cycle.

Cytarabine

Intervention Type: DRUG

Prophase: Intravenously on days 1-3. Induction: Intrathecal on days 15 or 18. Consolidation IB: Intravenously or subcutaneous on days 2-5 and 9-12. Consolidation IC: Intravenously every 12 hours starting on day 1 CNS Therapy: Intrathecal 4 times over 2 weeks. Consolidation II: Intrathecal once every 18 weeks Continuation: Intrathecal every 18 weeks

Methotrexate

Intervention Type: DRUG

Induction: Intravenously on day 6 and intrathecally on day 29 or 32. Consolidation IA: Intravenously on day 1 and intrathecally on Day 1 (prior to IV).

Consolidation IB: Intrathecally on day 1. CNS Therapy: Intrathecally 4 times over 2 weeks. Consolidation: Intrathecally once every 18 weeks. Continuation: Intravenously weekly and intrathecally every 18 weeks.

Vincristine

Intervention Type: DRUG

Induction: Intravenously on days 4, 11, 18, 25. Consolidation IA: Intravenously on day 1. CNS Therapy: Intravenously on day 1. Consolidation II: Intravenously on day 1 of each cycle.

Cyclophosphamide

Intervention Type: DRUG

Consolidation IB: Intravenously on day 1

Methylprednisone

Intervention Type: DRUG

Prophase: Intravenously on days 1-3

Hydrocortisone Sodium Succinate

Intervention Type: DRUG

Induction: Intrathecally on day 15 or 18. CNS Therapy: Intrathecally 4 times over 2 weeks. Consolidation II: Intrathecally once every 18 weeks. Continuation: Intrathecally every 18 weeks.

Dexamethasone

Intervention Type: DRUG

Consolidation IC: Orally on days 1-5 twice per day. Consolidation II: Orally on days 1-5 of each cycle. Continuation: Orally on days 1-5 of each cycle.

6-MP

Intervention Type: DRUG

Induction: Orally on days 3-43 or 33-46. Consolidation IA: orally on days 1-14. Consolidation IB: orally on days 1-14. CNS Therapy: Orally on days 1-14. Consolidation II: Orally on days 1-14. Continuation: Orally on days 1-14 of each cycle.

PEG-Asparaginase

Intervention Type: DRUG

Consolidation IC: Intravenously every 3 weeks, starting on day 8. CNS Therapy: Intravenously every 3 weeks, starting 3 weeks after the Consolidation IC dose.

Consolidation II: Intravenously every 3 weeks.

Imatinib

Intervention Type: DRUG

Used for PH+ ALL subjects enrolled prior to May 1st 2011 only and is used continuously throughout every phase of treatment.

Etoposide

Intervention Type: DRUG

Consolidation IC: intravenously on days 3, 4 and 5 of this cycle.

Radiation Therapy

Intervention Type: PROCEDURE

Given during CNS Therapy either 8 or 10 daily treatments, on days 1-8 or 1-10, depending upon leukemia involvement in the CSF

E. coli Asparaginase

Intervention Type: DRUG

Intramuscularly Day 7 of Induction.

Interventions

Doxorubicin

Induction: Intravenously on days 4 and 5. Consolidation 1A: Intravenously on day 1. CNS Therapy: Intravenously on day 1. Consolidation II: Intravenously day 1 of each cycle.

Intervention Type: DRUG

Cytarabine

Prophase: Intravenously on days 1-3. Induction: Intrathecal on days 15 or 18. Consolidation IB: Intravenously or subcutaneous on days 2-5 and 9-12. Consolidation IC: Intravenously every 12 hours starting on day 1 CNS Therapy: Intrathecal 4 times over 2 weeks. Consolidation II: Intrathecal once every 18 weeks Continuation: Intrathecal every 18 weeks

Intervention Type: DRUG

Methotrexate

Induction: Intravenously on day 6 and intrathecally on day 29 or 32. Consolidation IA: Intravenously on day 1 and intrathecally on Day 1 (prior to IV).

Consolidation IB: Intrathecally on day 1. CNS Therapy: Intrathecally 4 times over 2 weeks. Consolidation: Intrathecally once every 18 weeks. Continuation: Intravenously weekly and intrathecally every 18 weeks.

Intervention Type: DRUG

Vincristine

Induction: Intravenously on days 4, 11, 18, 25. Consolidation IA: Intravenously on day 1. CNS Therapy: Intravenously on day 1. Consolidation II: Intravenously on day 1 of each cycle.

Intervention Type: DRUG

Cyclophosphamide

Consolidation IB: Intravenously on day 1

Intervention Type: DRUG

Methylprednisone

Prophase: Intravenously on days 1-3

Intervention Type: DRUG

Hydrocortisone Sodium Succinate

Induction: Intrathecally on day 15 or 18. CNS Therapy: Intrathecally 4 times over 2 weeks. Consolidation II: Intrathecally once every 18 weeks. Continuation: Intrathecally every 18 weeks.

Intervention Type: DRUG

Dexamethasone

Consolidation IC: Orally on days 1-5 twice per day. Consolidation II: Orally on days 1-5 of each cycle. Continuation: Orally on days 1-5 of each cycle.

Intervention Type: DRUG

6-MP

Induction: Orally on days 3-43 or 33-46. Consolidation IA: orally on days 1-14. Consolidation IB: orally on days 1-14. CNS Therapy: Orally on days 1-14. Consolidation II: Orally on days 1-14. Continuation: Orally on days 1-14 of each cycle.

Intervention Type: DRUG

PEG-Asparaginase

Consolidation IC: Intravenously every 3 weeks, starting on day 8. CNS Therapy: Intravenously every 3 weeks, starting 3 weeks after the Consolidation IC dose.

Consolidation II: Intravenously every 3 weeks.

Intervention Type: DRUG

Imatinib

Used for PH+ ALL subjects enrolled prior to May 1st 2011 only and is used continuously throughout every phase of treatment.

Intervention Type: DRUG

Etoposide

Consolidation IC: intravenously on days 3, 4 and 5 of this cycle.

Intervention Type: DRUG

Radiation Therapy

Given during CNS Therapy either 8 or 10 daily treatments, on days 1-8 or 1-10, depending upon leukemia involvement in the CSF

Intervention Type: PROCEDURE

E. coli Asparaginase

Intramuscularly Day 7 of Induction.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Boston Children's Hospital

OTHER

Sponsor Role: collaborator

NCIC Clinical Trials Group

NETWORK

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Daniel J. DeAngelo, MD, PhD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Daniel DeAngelo, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

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

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, United States

Ohio State University Medical Center

Columbus, Ohio, United States

LDS Hospital

Salt Lake City, Utah, United States

Vancouver Cancer Center

Vancouver, British Columbia, Canada

Cancer Care Manitoba

Winnipeg, Manitoba, Canada

The Moncton Hospital

Moncton, New Brunswick, Canada

QEII, Health Sciences Centre

Halifax, Nova Scotia, Canada

Hopital Charles LeMoyne

Greenfield Park, Quebec, Canada

Hopital Maisonneuve Rosemont

Montreal, Quebec, Canada

Hopital Notre-Dame

Montreal, Quebec, Canada

McGill University Department of Oncology

Montreal, Quebec, Canada

Countries

United States; Canada

Other Identifiers

06-254

Identifier Type: -

Identifier Source: org_study_id