ALL Adult Consortium Trial: Adult ALL Trial

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

ALL Adult Consortium Trial: Adult ALL Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00476190
• Other study ID #: 06-254
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 2007
• Est. completion date: December 2024

Study information

• Verified date: April 2024
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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>

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 112
• Est. completion date: December 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• 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.
• 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
• 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.
• 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.
• Cyclophosphamide
Consolidation IB: Intravenously on day 1
• Methylprednisone
Prophase: Intravenously on days 1-3
• 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.
• 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.
• 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.
• 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.
• Imatinib
Used for PH+ ALL subjects enrolled prior to May 1st 2011 only and is used continuously throughout every phase of treatment.
• Etoposide
Consolidation IC: intravenously on days 3, 4 and 5 of this cycle.

Procedure:
• 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

Drug:
• E. coli Asparaginase
Intramuscularly Day 7 of Induction.

Locations

Country	Name	City	State
Canada	Hopital Charles LeMoyne	Greenfield Park	Quebec
Canada	QEII, Health Sciences Centre	Halifax	Nova Scotia
Canada	The Moncton Hospital	Moncton	New Brunswick
Canada	Hopital Maisonneuve Rosemont	Montreal	Quebec
Canada	Hopital Notre-Dame	Montreal	Quebec
Canada	McGill University Department of Oncology	Montreal	Quebec
Canada	Vancouver Cancer Center	Vancouver	British Columbia
Canada	Cancer Care Manitoba	Winnipeg	Manitoba
United States	Beth Isreal Deaconess Medical Center	Boston	Massachusetts
United States	Children's Hospital of Boston	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	New York	New York
United States	LDS Hospital	Salt Lake City	Utah

Sponsors (4)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	Boston Children's Hospital, Massachusetts General Hospital, NCIC Clinical Trials Group

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the feasibility, toxicity and efficacy of the high-risk pediatric treatment in adult patient 18 year of age or older.		3 years
Secondary	To determine the complete response rate at the end of induction therapy.		2 years
Secondary	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
Secondary	Overall survival, defined as time from study entry to death from any cause, will be estimated using Kaplan-Meier methods.		3 years